Metallothionein induction reduces caspase-3 activity and TNFα levels with preservation of cognitive function and intact hippocampal neurons in carmustine-treated rats

Hippocampal integrity is essential for cognitive functions. On the other hand, induction of metallothionein (MT) by ZnSO4 and its role in neuroprotection has been documented. The present study aimed to explore the effect of MT induction on carmustine (BCNU)-induced hippocampal cognitive dysfunction in rats. A total of 60 male Wistar albino rats were randomly divided into four groups (15/group): The control group injected with single doses of normal saline (i.c.v) followed 24 h later by BCNU solvent (i.v). The second group administered ZnSO4 (0.1 µmol/10 µl normal saline, i.c.v, once) then BCNU solvent (i.v) after 24 h. Third group received BCNU (20 mg/kg, i.v, once) 24 h after injection with normal saline (i.c.v). Fourth group received a single dose of ZnSO4 (0.1 µmol/10 µl normal saline, i.c.v) then BCNU (20 mg/kg, i.v, once) after 24 h. The obtained data revealed that BCNU administration resulted in deterioration of learning and short-term memory (STM), as measured by using radial arm water maze, accompanied with decreased hippocampal glutathione reductase (GR) activity and reduced glutathione (GSH) content. Also, BCNU administration increased serum tumor necrosis factor-alpha (TNFα), hippocampal MT and malondialdehyde (MDA) contents as well as caspase-3 activity in addition to histological alterations. ZnSO4 pretreatment counteracted BCNU-induced inhibition of GR and depletion of GSH and resulted in significant reduction in the levels of MDA and TNFα as well as the activity of caspase-3. The histological features were improved in hippocampus of rats treated with ZnSO4 + BCNU compared to only BCNU-treated animals. In conclusion, MT induction halts BCNU-induced hippocampal toxicity as it prevented GR inhibition and GSH depletion and counteracted the increased levels of TNFα, MDA and caspase-3 activity with subsequent preservation of cognition

Pro-inflammatory and oxidative stress pathways which compromise sperm motility and survival may be altered by L-carnitine

The testis is an immunologically privileged organ. Sertoli cells can form a blood-testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s) is poorly understood. Our objective is to help in understanding such mechanism(s) to develop protective agents against temporary or permanent testicular dysfunction. Lipopolysaccaride (LPS) is used as a model of animal sepsis while L-carnitine (LCR) is used as a protective agent. A total of 60 male Swiss albino rats were divided into four groups (15/group). The control group received Saline; the 2nd group was given LCR (500 mg/kg i.p, once). The third group was treated with LPS (5 mg/kg i.p once) and the fourth group received LCR then LPS after three hours. From each group, five rats were used for histopathological examination. Biochemical parameters were assessed in the remaining ten rats. At the end of the experiment, animals were lightly anaesthetized with ether where blood samples were collected and testes were dissected on ice. Sperm count and motility were evaluated from cauda epididymis in each animal. Also, oxidative stress was evaluated by measuring testicular contents of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-HDG, the DNA adduct for oxidative damage) in testicular DNA. The pro-inflammatory mediator nitric oxide (NO) in addition to lactate dehydrogenase (LDHx) isoenzyme-x activity as an indicator for normal spermatozoal metabolism were assessed in testicular homogenate. Serum interlukin (IL)-2 level was also assessed as a marker for T-helper cell function. The obtained data revealed that LPS induced marked reductions in sperm's count and motility, obstruction in seminiferous tubules, hypospermia and dilated congested blood vessels in testicular sections concomitant with decreased testicular GSH content and LDHx activity. Moreover, the testicular levels of MDA, 8-HDG (in testicular DNA) and NO as well as serum IL-2 level were increased. Administration of LCR before LPS returned both sperm count and motility to normal levels. Also, contents of testicular GSH, MDA, 8-HDG and NO returned back to the corresponding control values. In addition, serum IL-2 level as well as histological abnormalities were markedly improved in LCR + LPS-treated rats. In conclusion, LPS increased proinflammatory and oxidative stress markers in the testis leading to a marked testicular dysfunction. L-carnitine administration ameliorates these effects by antioxidant and/or anti-inflammatory mechanisms suggesting a protective role against male infertility in severely infected or septic patients

Prevalence and indicators of vitamin B12 insufficiency among young women of childbearing age

Vitamin B12 insufficiency is a global health issue among women of childbearing age, yet few studies have investigated its prevalence and risk factors among healthy Middle Eastern populations. This cross-sectional study included 346 Saudi women aged 19–30 years and enrolled at King Saud University, Riyadh, Saudi Arabia. A series of questionnaires were administered to record the study participants’ sociodemographic status, medical history, dietary intake, and physical activity. Participants’ anthropometric data were also recorded and their fasting blood samples were analyzed. The rate of vitamin B12 insufficiency (≤220 pmol/L) was approximately 6% among the study participants. After adjusting for confounding factors, it was observed that the risk factors for vitamin B12 insufficiency included daily sitting time ≥ 7 h, low income (2.4 mcg/day) has been shown to confer reasonable protection against vitamin B12 insufficiency. These study findings highlight that a combination of increased physical activity and dietary vitamin B12 intake above the current recommended dietary allowance may help improve the serum vitamin B12 levels of young women of childbearing age, especially those with a low socioeconomic status. Timely detection and protection against vitamin B12 insufficiency in this subpopulation are important to prevent maternal and fetal health risks

Reasons for and patterns relating to the extraction of permanent teeth in a subset of the Saudi population

Khalil Alesia,1 Hesham S Khalil2 1Department of Prosthetic Dental Sciences, 2Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Saudi Arabia Background: The purpose of this study was to investigate the reasons for and patterns of extraction of permanent teeth in a subset of the Saudi population. Methods: During a 3-month period, dentists were asked to record, using a specially designed survey form, the reasons for every extraction of a permanent tooth. The reasons for tooth extraction were assigned to different causes, ie, dental caries, periodontal disease, eruption problems, trauma, orthodontics, failed root canal treatment, and others. The data requested for each extraction were: patient age, gender, nationality, and type of tooth removed and the reason for its extraction. Results: The highest percentage of extractions was observed in young females aged 10–30 years. Presence of caries was observed to be the main reason for extraction (50.2%) followed by orthodontic problems (18.2%), eruption problems (17.5%), and periodontal problems (8.2%). The most frequently extracted posterior teeth were the third mandibular molar (19.4%), the third maxillary molar (16.4%), the first maxillary premolar (13.2%), and the first mandibular molar (10.9%). Conclusion: Dental caries was found to be the most common reason for extraction of teeth. Molar teeth were found to be the most frequently extracted, with an increased number of extracted first premolars as a result of orthodontic treatment. The highest percentage of extractions was observed in young females aged 10–30 years. Keywords: extraction, Saudi, teeth, reasons, permanen

Asymmetric Recovery in Cerebellar-Deficient Mice Following Unilateral Labyrinthectomy

The term “vestibular compensation” refers to the resolution of motor deficits resulting from a peripheral vestibular lesion. We investigated the role of the cerebellum in the compensation process by characterizing the vestibuloocular reflex (VOR) evoked by head rotations at frequencies and velocities similar to those in natural behaviors in wild-type (WT) versus cerebellar-deficient Lurcher (Lc/+) mice. We found that during exploratory activity, normal mice produce head rotations largely consisting of frequencies ≤4 Hz and velocities and accelerations as large as 400°/s and 5,000°/s2, respectively. Accordingly, the VOR was characterized using sinusoidal rotations (0.2–4 Hz) as well as transient impulses (∼400°/s; ∼2,000°/s2). Before lesions, WT and Lc/+ mice produced similar VOR responses to sinusoidal rotation. Lc/+ mice, however, had significantly reduced gains for transient stimuli. After unilateral labyrinthectomy, VOR recovery followed a similar course for WT and Lc/+ groups during the first week: gain was reduced by 80% for ipsilesionally directed head rotations on day 1 and improved for both strains to values of ∼0.4 by day 5. Moreover, responses evoked by contralesionally directed rotations returned to prelesion in both strains within this period. However, unlike WT, which showed improving responses to ipsilesionally directed rotations, recovery plateaued after first week for Lc/+ mice. Our results show that despite nearly normal recovery in the acute phase, long-term compensation is compromised in Lc/+. We conclude that cerebellar pathways are critical for long-term restoration of VOR during head rotation toward the lesioned side, while noncerebellar pathways are sufficient to restore proper gaze stabilization during contralesionally directed movements

Cost Optimization of DNAPL Remediation at Dover Air Force Base Site

This study investigates stochastic optimization of dense nonaqueous phase liquid (DNAPL) remediation design at Dover Air Force Base Area 5 using emulsified vegetable oil (EVO) injection. The Stochastic Cost Optimization Toolkit (SCOToolkit) is used for the study, which couples semianalytical DNAPL source depletion and transport models with parameter estimation, error propagation, and stochastic optimization modules that can consider multiple sources and remediation strategies. Model parameters are calibrated to field data conditions on prior estimates of parameters and their uncertainty. Monte Carlo simulations are then performed to identify optimal remediation decisions that minimize the expected net present value (NPV) cleanup cost while maintaining concentrations at compliance wells under the maximum contaminant level (MCL). The results show that annual operating costs could be reduced by approximately 50% by implementing the identified optimal remediation strategy. We also show that recalibration and reoptimization after 50 years using additional monitoring data could lead to a further 60% reduction in annual operating cost increases the reliability of the proposed remediation actions. © 2012, The Author(s). Ground Water Monitoring & Remediation © 2012, National Ground Water Association

Metallothionein Induction Reduces Caspase-3 Activity and Tnfα Levels with Preservation of Cognitive Function and Intact Hippocampal Neurons in Carmustine-Treated Rats

Hippocampal integrity is essential for cognitive functions. On the other hand, induction of metallothionein (MT) by ZnSO4 and its role in neuroprotection has been documented. The present study aimed to explore the effect of MT induction on carmustine (BCNU)-induced hippocampal cognitive dysfunction in rats. A total of 60 male Wistar albino rats were randomly divided into four groups (15/group): The control group injected with single doses of normal saline (i.c.v) followed 24 h later by BCNU solvent (i.v). The second group administered ZnSO4 (0.1 µmol/10 µl normal saline, i.c.v, once) then BCNU solvent (i.v) after 24 h. Third group received BCNU (20 mg/kg, i.v, once) 24 h after injection with normal saline (i.c.v). Fourth group received a single dose of ZnSO4 (0.1 µmol/10 µl normal saline, i.c.v) then BCNU (20 mg/kg, i.v, once) after 24 h. The obtained data revealed that BCNU administration resulted in deterioration of learning and short-term memory (STM), as measured by using radial arm water maze, accompanied with decreased hippocampal glutathione reductase (GR) activity and reduced glutathione (GSH) content. Also, BCNU administration increased serum tumor necrosis factor-alpha (TNFα), hippocampal MT and malondialdehyde (MDA) contents as well as caspase-3 activity in addition to histological alterations. ZnSO4 pretreatment counteracted BCNU-induced inhibition of GR and depletion of GSH and resulted in significant reduction in the levels of MDA and TNFα as well as the activity of caspase-3. The histological features were improved in hippocampus of rats treated with ZnSO4 + BCNU compared to only BCNU-treated animals. In conclusion, MT induction halts BCNU-induced hippocampal toxicity as it prevented GR inhibition and GSH depletion and counteracted the increased levels of TNFα, MDA and caspase-3 activity with subsequent preservation of cognition