Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation in individuals consuming little or no alcohol, has become highly prevalent globally. Oxidative stress plays a central role in instigating inflammation and cell death pathways driving NAFLD progression. This case-control study aimed to elucidate the association between circulating levels of the pivotal non-enzymatic antioxidants - coenzyme Q10 and vitamins E and C - and liver injury parameters among 60 Iraqi NAFLD patients versus 30 healthy controls. NAFLD diagnosis entailed over 5% hepatic steatosis on ultrasound excluding other etiologies. Patients spanned three age groups: 20-29, 30-39, and 40-49. Substantially diminished antioxidant levels concurrent with elevated alkaline phosphatase enzyme were unveiled in NAFLD patients relative to controls (all p < 0.001). Age-based analysis reinforced widespread antioxidant depletion and liver enzyme augmentation across NAFLD patients. Significant correlations also emerged between antioxidants and liver parameters. Our novel observations confirm an antioxidant inadequacy likely perpetuating pathogenic oxidative reactions in NAFLD. Restoring such deficits through lifestyle or therapeutic interventions may confer preventative and disease-modifying value.

Therapeutic efficacy of matrix metalloproteinase-12 suppression on neurological recovery after ischemic stroke: Optimal treatment timing and duration.

We recently showed that the post-ischemic induction of matrix metalloproteinase-12 (MMP-12) in the brain degrades tight junction proteins, increases MMP-9 and TNFα expression, and contributes to the blood-brain barrier (BBB) disruption, apoptosis, demyelination, and infarct volume development. The objectives of this study were to (1) determine the effect of MMP-12 suppression by shRNA-mediated gene silencing on neurological/functional recovery, (2) establish the optimal timing of MMP-12shRNA treatment that provides maximum therapeutic benefit, (3) compare the effectiveness of acute versus chronic MMP-12 suppression, and (4) evaluate potential sex-related differences in treatment outcomes. Young male and female Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and reperfusion. Cohorts of rats were administered either MMP-12shRNA or scrambled shRNA sequence (control) expressing plasmids (1 mg/kg; i.v.) formulated as nanoparticles. At designated time points after reperfusion, rats from various groups were subjected to a battery of neurological tests to assess their reflex, balance, sensory, and motor functions. Suppression of MMP-12 promoted the neurological recovery of stroke-induced male and female rats, although the effect was less apparent in females. Immediate treatment after reperfusion resulted in a better recovery of sensory and motor function than delayed treatments. Chronic MMP-12 suppression neither enhanced nor diminished the therapeutic effects of acute MMP-12 suppression, indicating that a single dose of plasmid may be sufficient. We conclude that suppressing MMP-12 after an ischemic stroke is a promising therapeutic strategy for promoting the recovery of neurological function.

Effect of convergence on the horizontal VOR in normal subjects and patients with peripheral and central vestibulopathy.

BACKGROUND: Vestibular compensatory eye movements provide visual fixation stabilization during head movement. The anatomic pathways mediating a normal horizontal vestibulo-ocular reflex (h-VOR), when lesioned, cause spontaneous nystagmus. While previous reports address the effect of convergence on different spontaneous nystagmus types, to our knowledge, a study of acute vestibular nystagmus suppression viewing near targets comparing patients with peripheral or central vestibular lesions has not been previously reported. METHODS: We attempt to clarify potential vestibular and near-reflex interaction by comparing near and far h-VOR gain in 19 healthy controls, six patients with acute/subacute peripheral vestibular lesion (PVL), and one patient with unilateral vestibular nuclear lesion (VNL) in the pontine tegmentum. RESULTS: The horizontal (h)-VOR in normal subjects increased with convergence in both eyes (P = 0.027, P < 0.001). In unilateral PVL patients, gain failed to increase in either direction (P = 0.25, P = 0.47). In contrast, when fixating at 15 cm, the h-aVOR in the VNL lesion, gain did not increase, and a right h-nystagmus developed. Even though we found inability to increase gain in PVL with near target fixation, this did not interfere with h-nystagmus suppression upon converging. Our VNL patient had normal h-nystagmus suppression viewing far distance targets and lacked near target h-nystagmus suppression. CONCLUSION: We hypothesize that normal IO/flocculus pathway suppressed spontaneous nystagmus in PVL. Impaired h-VOR near adaptation in the medial vestibular nucleus was responsible for h-nystagmus direction with fixation block. Additionally, impaired viewing distance estimate contributed to near h-nystagmus suppression failure.

A Single Test to Study Social Behavior and Repetitive Self-grooming in Mice.

The ability to recognize and interact with members of the same species is essential for social communication. Investigating the neural substrates of social interest and recognition may offer insights into the behavioral differences present in disorders affecting social behavior. Assays used to study social interest in rodents include the 3-chamber test, a partition test, and a social interaction test. Here, we present a single protocol that can be used to quantify the level of social interest displayed by mice, the ability to distinguish between different individual mice (social recognition), and the level of repetitive self-grooming displayed. In the first part of the protocol, a social habituation/dishabituation test, the time spent by a test mouse sniffing a stimulus mouse is quantified over 9 trials. In the first 8 interactions, the same stimulus mouse is used repeatedly; on the ninth trial, a novel stimulus mouse is presented. Intact social recognition is indicated by a progressive decrease in the investigation time over trials 1-8, and an increase in trial 9. The interval between each social trial is used to quantify self-grooming, a stereotyped repetitive behavior in mice. We also present a method for randomized, blinded analysis of these behaviors to increase rigor and reproducibility of results. Therefore, this single behavioral test enables ready assessment of phenotypes of both social and repetitive behaviors in an integrated manner in the same animals. This feature can be advantageous in understanding interactions between these behaviors and phenotypes in mouse models with genetic variants associated with autism and other neurodevelopmental or neuropsychiatric disorders, which are often characterized by these behavioral differences.

Differential impacts on multiple forms of spatial and contextual memory in diazepam binding inhibitor knockout mice.

Learning and memory are fundamental processes that are disrupted in many neurological disorders including Alzheimer's disease and epilepsy. The hippocampus plays an integral role in these functions, and modulation of synaptic transmission mediated by γ-aminobutyric acid (GABA) type-A receptors (GABAA Rs) impacts hippocampus-dependent learning and memory. The protein diazepam binding inhibitor (DBI) differentially modulates GABAA Rs in various brain regions, including hippocampus, and changes in DBI levels may be linked to altered learning and memory. The effects of genetic loss of DBI signaling on these processes, however, have not been determined. In these studies, we examined male and female constitutive DBI knockout mice and wild-type littermates to investigate the role of DBI signaling in modulating multiple forms of hippocampus-dependent spatial learning and memory. DBI knockout mice did not show impaired discrimination of objects in familiar and novel locations in an object location memory test, but did exhibit reduced time spent exploring the objects. Multiple parameters of Barnes maze performance, testing the capability to utilize spatial reference cues, were disrupted in DBI knockout mice. Furthermore, whereas most wild-type mice adopted a direct search strategy upon learning the location of the target hole, knockout mice showed higher rates of using an inefficient random strategy. In addition, DBI knockout mice displayed typical levels of contextual fear conditioning, but lacked a sex difference observed in wild-type mice. Together, these data suggest that DBI selectively influences certain forms of spatial learning and memory, indicating novel roles for DBI signaling in modulating hippocampus-dependent behavior in a task-specific manner.

Effect of nanoclay concentration level on the electrical properties of polypropylene under electron irradiation in a SEM.

For studying the electrical properties (charge trapping, transport and secondary electron emission) of the polypropylene-based nanocomposites with different contents of natural clay, the specimens were submitted to electron irradiation of a scanning electron microscope. A device, suitably mounted on the sample holder of the scanning electron microscope, was used to measure two currents (i.e. leakage and displacement currents) induced in the polypropylene-based nanocomposites (polymer nanocomposites) under electron irradiation. The evolution of trapped charge during irradiation for each type of studied polymer nanocomposites is deduced. The amount of trapped charge at the steady state is also determined by measuring the change of secondary electron image size associated to the electron trajectory simulation. It is found, surprisingly, that not only the leakage current increases as a function of clay loading level but also trapped charge. However, this could be related to the increase of conductivity in one hand and to proliferation of interfaces between nanoparticles and neighbouring materials on the other hand. These two processes play crucial role in controlling the carrier transport (through polymer nanocomposites or/and along its surface) closely related to the charge storage and leakage current. Additional experiment using dielectric spectroscopy were performed to show the effect of clay concentration in changing the dielectric relaxation behaviour and to evidence the existence of interfaces between nanoparticles and polymer. The secondary electron emission during electron irradiation is also studied through the total electron yield that is deduced by correlating the measured leakage and displacement currents.

Embryonic exposure to dimethoate and/or deltamethrin impairs sexual development and programs reproductive success in adult male offspring mice.

Pesticides can be toxic to desirable plants and animals, including humans. The aim of this study was to investigate the reproductive effects of low doses of pesticides on male offspring of exposed pregnant mice. Three groups of five female mice were treated daily by oral gavage with dimethoate (5 mg kg(-1) per day), deltamethrin (5 mg kg(-1) per day) and their mixture at 5 mg kg(-1) per day from day 3 to day 21 of pregnancy. Fertility, sexual behaviour and a number of reproductive endpoints, such as organ weights, sperm evaluations and testicular histology, were examined on four adult male offspring of exposed pregnant mice. When compared with control, a dose of deltamethrin 5 mg kg j(-1) causes a decrease in the absolute and relative weight of the testes of exposed mice and it affects their fertility by reducing the density, mobility and vitality of sperm and increasing the number of abnormal forms of these cells (P ≤ 0.01). The same results were obtained in mice exposed to a dose of 5 mg kg j(-1) combination of dimethoate and deltamethrin. This study demonstrated that deltamethrin and combination of dimethoate and deltamethrin caused a decrease in the absolute and relative weight of the testes, which affected the sperm parameters of male offspring of exposed mice to a low dose of these pesticides during pregnancy.

An in vitro study on reproductive toxicology of Deltamethrin on rat spermatozoa.

Recent findings indicate that synthetic pyrethroid insecticide may induce toxic manifestations by enhancing the production of reactive oxygen species and disrupting the balance between pro-oxidants and antioxidants as a result of lipid peroxidation (LP) of cell membranes. The aim of the study was to examine the potency of Deltamethrin (Del) to induce oxidative stress response in rat spermatozoa in vitro. Spermatozoa were incubated with different concentrations (0, 10, 50, 100 and 200 microm) of Del for 3 h at 37 degrees C. After that, sperm parameters (motility, viability and abnormal morphology), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined. We found that in vitro exposure to Del caused a significant decline of sperm motility and viability and increase of abnormal sperm morphology, MDA, SOD and CAT levels at different concentrations of Del. This study demonstrated that Del caused deterioration in sperm motility and viability, and induction in LP, abnormal morphology of spermatozoa and antioxidants enzyme activities.

Comparative effects of dimethoate and deltamethrin on reproductive system in male mice.

The effects of dimethoate (5, 15 and 28 mg kg(-1) day(-1)), deltamethrin (5 mg kg(-1) day(-1)) and their mixture (5 mg kg(-1) day(-1)) on male reproduction in mice were studied. The insecticides were given orally by gavage to male mice for 21 days. At the end of the treatment period, body, testes and epididymides weights and sperm parameters were determined. Alone mixture treatment has significantly decreased body weights. Dimethoate at 28 mg kg(-1) day(-1), deltamethrin at 5 mg kg(-1) day(-1) and their mixture at 5 mg kg(-1) day(-1) were associated with a significantly decreased sperm count, motility and viability and significantly increased percent morphologically abnormal spermatozoa compared with the controls. This study demonstrated the adverse effects of dimethoate at high dose, deltamethrin and their combining at 5 mg kg(-1) day(-1) on reproductive system and sperm parameters in male mice.

Semen quality decline among men in infertile relationships: experience over 12 years in the South of Tunisia.

Concerns about the worldwide decline in semen quality over the past 50 years are increasing. Western countries have shown a decline in semen quality. However, in non-Western countries studies are sparse. We investigated trends in semen parameters between 1996 and 2007 in the Sfax area of southern Tunisia in a sample of 2940 men in infertile relationships. Age at semen collection, duration of sexual abstinence, volume of seminal fluid, the sperm count, percentages of motile and morphologically normal spermatozoa, and semen leukocyte concentration were determined. Linear regression was used to examine trends over time in sperm count, sperm motility, normal morphology, and semen leukocyte concentration. Mean age and semen volume did not change between 1996 and 2007. Data adjusted for age and abstinence showed a decreasing trend in sperm count and percentage of normal morphology over the last 12 years (R(2) = 0.71, P = .0004, and R(2) = 0.87, P < .0001, respectively). There was no significant change in sperm motility. However, semen leukocyte concentration increased significantly over time (R(2) = 0.38, P = .03). These results coincide with the high prevalence of genital infectious diseases in the Sfax area, suggesting that infection may be a potential contributing factor in semen quality decline.

Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men.

Numerous studies have reported beneficial effects of antioxidant drugs on semen quality, but there is no well-defined therapeutical protocol in male infertility. This study aimed to test the effects of vitamin E and selenium supplementation on lipid peroxidation and on sperm parameters. The study included 54 voluntary and infertile men who produced semen samples for spermiogram and for spectrophotometric measurement of a lipid peroxidation marker, the malondialdehyde (MDA), and produced blood samples for high-performance liquid chromatography assessment of serum vitamin E level. The trial was randomized and open. Twenty-eight men were supplemented daily by vitamin E (400 mg) and selenium (225 microg), during 3 months. The remaining 26 patients received vitamin B (4,5 g/day) for the same duration. Only 20 patients achieved their treatment and returned for control analysis. MDA concentrations in sperm were much less than in seminal plasma and motility and viability were inversely correlated with semen MDA levels. In contrast to vitamin B supplementation, vitamin E and selenium supplementation produced a significant decrease in MDA concentrations and an improvement of sperm motility. The results confirm the protective and beneficial effects of vitamin E and selenium on semen quality and advocate their use in male infertility treatment.

Chlamydia trachomatis and male infertility in Tunisia.

OBJECTIVE: Chlamydia trachomatis is a common sexually transmitted micro-organism. The impact of chlamydial infection on semen parameters and male fertility is controversial. Our purpose was to determine the prevalence of C. trachomatis in the male partners of infertile couples in Tunisia and to assess the relationship between chlamydial infection markers and male infertility. METHODS: Chlamydial DNA in urethral and in semen specimens was determined by using the Cobas Amplicor polymerase chain reaction (PCR) assay and chlamydial immunoglobulin G (IgG) antibodies were measured by micro-immunofluorescence in serum samples in 92 male partners, with or without pathological standard semen parameters, according to the guidelines of the World Health Organization (sperm count, progressive sperm motility, sperm morphology and sperm viability). In parallel, chlamydial infection markers in endocervical material were determined by PCR and chlamydial IgG antibodies were measured by micro-immunofluorescence in serum samples from the female partners of the patients. RESULTS: C. trachomatis was found in 35.9% (33/92) of the male partners of the infertile couples and in 38% (35/92) of their female partners. There was a significant correlation between the detection of C. trachomatis in both partners (p = 0.004). C. trachomatis DNA was detected in 18.5% (17/92) of urethral specimens and in 16.3% (15/92) of semen specimens. Chlamydial IgG antibodies were present in 9.8% (9/92) of the serum samples. A standard semen analysis showed that 88% (81/92) were pathological. Sperm viability, progressive sperm motility, morphology and sperm concentration were abnormal in 73.8%, 70.2%, 34.5% and 13%, respectively, of the 92 evaluated semen specimens. Comparison of the parameters of the standard semen analysis between the male partners of the infertile couples with or without chlamydial infection markers showed that only the presence of C. trachomatis DNA in semen samples can affect sperm motility. Parameters of the standard semen analysis were not significantly related either to the detection of chlamydial DNA in urethral samples or to the presence of serum chlamydial antibodies. CONCLUSION: Our results show that C. trachomatis seems to be widespread among the male partners of infertile couples in Tunisia and show that this organism can affect sperm motility and, thus, can play an important role in the etiology of male infertility.

[Colonoscopy with computed tomography with volume reconstruction. The results and a comparison with endoscopy and surgery]. / Colonscopia con Tomografia Computerizzata con ricostruzioni di volume. Risultati e confronto con endoscopia e chirurgia.

PURPOSE: Virtual CT colonoscopy is a novel technique whose diagnostic accuracy and clinical yield are currently investigated. Several studies have shown its capabilities in detecting colon and rectal cancers. We report the results of a preliminary experience with the volume rendering technique and compare CT colonoscopy with endoscopy and surgery. MATERIAL AND METHODS: Our series consisted of 25 patients with colon cancer confirmed at endoscopy and/or surgery. All examinations were carried out with a spiral CT scanner Philips Tomoscan AVE1. Intestinal preparation was adequate in all patients, consisting in gas insufflated immediately before acquisition, after the injection of 100 mL iodinated contrast agent. All examination were performed in prone position using axial 5 mm slices with 5 mm table feed (pitch 1) and 2 mm reconstruction index; 120 kV and 200-250 mA were used. Images were transferred to a workstation (Easy Vision, Philips, release 4.2.1.1) for processing. We acquired multiplanar (MPR) and virtual endoscopic images with volume rendering; the selected threshold was -250 to -600 Hounsfield Units. Virtual endoscopic images could be obtained in 23 of 25 cases. The results of the radiological study were compared with endoscopic and surgical findings in 25 and 17 cases, respectively. RESULTS: Endoscopy and surgery detected 46 lesions: 29 were malignant and 17 benign. Axial CT and MPR alone detected 35 lesions (76%), 29 of them malignant and 6 benign. The 11 benign lesions missed by axial CT ranged 6-8 mm in diameter. There were no false positives. CT colonoscopy alone detected 66 lesions, but 22 of them were false positive due to residual stool in the colon (21 cases) and to residual barium in the colon (1 case). Combining CT colonoscopy and axial and MPR images enabled to correct the false positive diagnoses made by CT colonoscopy alone and to decrease the false negative ratio of axial and MPR images. Forty-one of 44 lesions (93%) were detected. Thirty-seven lesions were found in the 17 surgical patients; 34 of them were correctly identified combining CT colonoscopy and axial and MPR findings, while endoscopy detected only 31 lesions. Thus, CT had 92% sensitivity, versus 83% of fiberoptic endoscopy. CONCLUSION: In this preliminary experience volume rendering CT colonoscopy exhibited high sensitivity in detecting colon cancers, but their correct evaluation and characterization can be obtained if axial and MPR studies are combined. Further investigation and technological developments are necessary to define the yield of this new technique.