Treatment of infantile spasms in Saudi Arabia.

OBJECTIVE: To evaluate the treatment approach and compliance of pediatric neurologists with evidence-based guidelines across Kingdom of Saudi Arabia (KSA). These guidelines that clarify the optimal management of infantile spasms (IS) are not widely followed for various practical reasons. METHODS: Physicians practicing in the field of pediatric neurology in KSA were contacted from the database of national societies. A cross-sectional study was conducted using a structured 20-item on-line survey designed to examine their clinical experience with IS and their treatment choices. RESULTS: A total of 52 pediatric neurologists completed the survey (69% estimated capture rate). They received their formal training within KSA (40%), North America (33%), or Europe (14%). The majority practiced in 2 major cities, Riyadh (46%) or Jeddah (19%). Vigabatrin was favored over adrenocorticotropic hormone (ACTH) as first line drug for patients without tuberous sclerosis complex (48% vs. 21%). Several factors correlated with correctly selecting ACTH as first line including western training (33% vs. 5%, p=0.001), practicing in the city of Riyadh (25% vs. 14%, p=0.001), or having >10 years of clinical experience (25% vs. 5%, p=0.017). Reasons for not complying with the recommended treatment guidelines included lack of availability of ACTH (42%), side effect profile of steroids (29%), and personal preferences (14%). Only 4% admitted lack of awareness of the currently published management guidelines. CONCLUSION: Many pediatric neurologists in KSA are not following the published IS management guidelines. Using ACTH as first line correlated with their training, practice location, and years of experience. Lack of drug availability and side effect profile were common reasons for not complying with the management guidelines.

Sleep extension is a feasible lifestyle intervention in free-living adults who are habitually short sleepers: a potential strategy for decreasing intake of free sugars? A randomized controlled pilot study.

Background: Evidence suggests that short sleep duration may be a newly identified modifiable risk factor for obesity, yet there is a paucity of studies to investigate this. Objective: We assessed the feasibility of a personalized sleep extension protocol in adults aged 18-64 y who are habitually short sleepers (5 to <7 h), with sleep primarily measured by wrist actigraphy. In addition, we collected pilot data to assess the effects of extended sleep on dietary intake and quality measured by 7-d food diaries, resting and total energy expenditure, physical activity, and markers of cardiometabolic health. Design: Forty-two normal-weight healthy participants who were habitually short sleepers completed this free-living, 4-wk, parallel-design randomized controlled trial. The sleep extension group (n = 21) received a behavioral consultation session targeting sleep hygiene. The control group (n = 21) maintained habitual short sleep. Results: Rates of participation, attrition, and compliance were 100%, 6.5%, and 85.7%, respectively. The sleep extension group significantly increased time in bed [0:55 hours:minutes (h:mm); 95% CI: 0:37, 1:12 h:mm], sleep period (0:47 h:mm; 95% CI: 0:29, 1:05 h:mm), and sleep duration (0:21 h:mm; 95% CI: 0:06, 0:36 h:mm) compared with the control group. Sleep extension led to reduced intake of free sugars (-9.6 g; 95% CI: -16.0, -3.1 g) compared with control (0.7 g; 95% CI: -5.7, 7.2 g) (P = 0.042). A sensitivity analysis in plausible reporters showed that the sleep extension group reduced intakes of fat (percentage), carbohydrates (grams), and free sugars (grams) in comparison to the control group. There were no significant differences between groups in markers of energy balance or cardiometabolic health. Conclusions: We showed the feasibility of extending sleep in adult short sleepers. Sleep extension led to reduced free sugar intakes and may be a viable strategy to facilitate limiting excessive consumption of free sugars in an obesity-promoting environment. This trial was registered at www.clinicaltrials.gov as NCT02787577.

The effect of repeated exposure to azamethiphos on survival and spawning in the American lobster (Homarus americanus).

The azamethiphos formulation Salmosan has been used to control sea lice on Atlantic salmon. To determine the effect of this pesticide on spawning in the American lobster, pre-ovigerous females acclimated to 13 degrees C were given biweekly 1-h exposures to Salmosan at concentrations of 1.25-10 microg/L azamethiphos. In March and April, four exposures to 1.25, 2.5, or 5.0 microg/L had no significant effect on survival or spawning incidence, while three or four exposures to 10 microg/L caused high mortality (43-100%). Spawning incidence in the surviving lobsters in the 10 microg/L groups was significantly reduced in the group given four treatments, but not in the group given three treatments. In December and January, four exposures to 10 microg/L azamethiphos had no significant effect on either survival or spawning incidence. The results demonstrate that repeated 1-h biweekly exposures to azamethiphos can have a negative effect on survival and spawning in female American lobsters. The response to this pesticide appears to be influenced by time of year, as well as concentration and number of exposures.

Seasonal lethality of the organophosphate pesticide, azamethiphos to female American lobster (Homarus americanus).

The organophosphate pesticide azamethiphos is the active ingredient in Salmosan, a product formerly registered in Canada for the treatment of cultured Atlantic salmon against infestations of the ectoparasite Lepeophtheirus salmonis. The 48-h LC50 of azamethiphos to female American lobsters was determined bimonthly for 2 years to determine whether the sensitivity of lobsters to azamethiphos varied with time of year, molt stage, or reproductive stage. The LC50's ranged from 0.61 to 3.24 microg/L. The lobsters were most sensitive to azamethiphos during the spawning and molting seasons which occur in the summer and early fall when seawater temperatures are highest. Testing of compounds on this species for regulatory purposes should take into account that there may be variations in sensitivity during the molt and reproductive cycles.

A regression model using sediment chemistry for the evaluation of marine environmental impacts associated with salmon aquaculture cage wastes.

This study was undertaken to develop an approach for modelling changes of sediment chemistry related to the accumulation of aquaculture waste. Metal composition of sediment Al, Cu, Fe, Li, Mn, and Zn; organic carbon and < 63 microm particles were used to determine the extent of detectable effects around the cage. This study showed marked differences in the sediment chemistry between aquaculture sites and the natural background: (1) negative correlations between sediment Cu and Zn with Al, (2) poor correlations between metals and Li, and (3) concentrations of Fe and Mn decreased with increased accumulation of organic carbon. There is a trend among normalised metals, organic carbon and particles related to normal, hypoxic and anoxic sediment conditions. The trends are useful for detecting and assessing the cumulative effects from aquaculture wastes to the marine environment. Lithium is less interactive with other metals in aquaculture sediments compared with the natural background sediments. Principal components analysis (PCA) was carried out on the metals, organic carbon, and particles to cluster the similarities of the variables so as to establish the predicted or adjusted environmental monitoring program (EMP) ratings. This approach, using the adjusted EMP rating based on sediment chemistry, yields a regression model with R2 = 0.945 compared to R2= 0.653 for the regression model using unadjusted EMP for assessing the environmental conditions.

Effects of water-borne 4-nonylphenol and 17beta-estradiol exposures during parr-smolt transformation on growth and plasma IGF-I of Atlantic salmon (Salmo salar L.).

4-Nonylphenol (4-NP) is an endocrine disrupting substance (EDS) capable of mimicking the action of 17beta-estradiol (E2). It has been hypothesized that 4-NP in a pesticide formulation is linked to historical declines in Canadian Atlantic salmon (Salmo salar L.) populations, with effects being related to exposure during parr-smolt transformation (PST). To test this hypothesis, Atlantic salmon smolts were exposed to pulse-doses of water-borne 4-NP (20 ug/l), sustained doses of water-borne E2 (100 ng/l) (positive control), or ethanol vehicle (negative control) in mid-May during the final stages of PST. Individually tagged smolts were then sampled at three times (June, July and October) to monitor subsequent growth in sea water and plasma insulin-like growth factor I (IGF-I) concentrations. Smolt weights and plasma IGF-I concentrations were both affected by E2 and 4-NP. The effects of E2 and 4-NP on mean smolt weights were most prominent in July and October [E2 (*98.1 +/- 2.8, *242.3 +/- 10.6 g), 4-NP (*102.1 +/- 3.1, 255.7 +/- 9.5 g), controls (112.5 +/- 2.8, 282.3 +/- 8.8 g)] (P < 0.05), while their effects on mean plasma IGF-I concentrations were most prominent in June and October [E2 (15.0 +/- 1.9, 28.4 +/- 1.8 ng/ml), 4-NP (*14.8 +/- 1.9, *21.6 +/- 1.7 ng/ml), controls (20.0 +/- 1.1, 31.1 +/- 2.0 ng/ml)] (P < 0.05). Additionally, results suggest that the mechanisms of action of E2 and 4-NP involve disruption in the GH/IGF-I axis, and that they may be different from each other. The effects of E2 and 4-NP on growth and plasma IGF-I concentrations observed in this study are ecologically significant because they evoke concerns for successful growth and survival of wild salmon smolts exposed to low levels of estrogenic substances that may occur from current discharges into rivers supporting sea-run salmon stocks.

Aquaculture-related trace metals in sediments and lobsters and relevance to environmental monitoring program ratings for near-field effects.

The study was undertaken to assess the marine environmental effects from feed and waste associated with aquaculture activities. Metal compositions of sediment, lobster, and feed were used to evaluate the extent of detectable effects at 0 m (under the cage) and 50 m distance. Sediments that were collected under the cages and were characterised as hypoxic or anoxic, showed elevated levels of Cu, Zn, organic carbon, and % <63 microm particles, and low Mn and Fe. At 50 m there was a major reduction in waste chemical impact. Using lobster, a bioindicator species, as a tool for detecting near-field impacts, showed accumulations of high Cu associated with active aquaculture sites. Chemical compositions and metal ratios normalised with organic carbon, were used to assess the sediment conditions associated with environmental monitoring program ratings (EMP--normal, hypoxic, and anoxic). Principal component analysis (PCA) was used to explore chemical data at all sites for differentiating normal, hypoxic and anoxic sediment conditions. Selected variables (Cu, Zn, Fe, Mn, organic carbon, and particles <63 microm) were sufficient for the PCA approach with >90% explainable variance of first two components. The groupings based on PCA and cluster analysis were similar to EMP classifications with some exceptions of mis-identification by EMP. The sediment chemistry components were valid indicators for evaluating marine environmental conditions and for assessing aquaculture operating sites. The developed techniques, using chemical variables in combination with EMP and the statistical approach should be useful to predict the effects of aquaculture practices and the suitability of aquaculture operations.

The lethality of Salmosan (Azamethiphos) to American lobster (Homarus americanus) larvae, postlarvae, and adults.

The pesticide formulation Salmosan (47.5% w/w azamethiphos) is currently registered for use, in Canada, to treat salmonids for infestations of the copepod parasites, Lepeophtheirus salmonis and Caligus elongatus (sea lice). Determination was made of the acute lethality of this product to the three larval stages, the first postlarval stage, and the adult of the American lobster (Homarus americanus), a species of significant economic importance in Eastern Canada. The 48-h LC50 (as azamethiphos) is 3.57 microg/liter for Stage I, 1.03 microg/liter for Stage II, 2.29 microg/liter for Stage III, 2.12 microg/liter for Stage IV (the first postlarval stage), and 1.39 microg/liter for adults. These concentrations are not significantly different from each other, although the variability in response is greater in the larval stages than in the postlarvae or adults. These data when interpreted in conjunction with known physical oceanographic data and chemical dispersion studies indicate that single anti-louse treatments are unlikely to result in mortality among lobsters in the vicinity of salmon farms. However, the sublethal effects of this product and the effects of repeated exposures have yet to be determined.

Lethality of pyrethrins to larvae and postlarvae of the American lobster (Homarus americanus).

Pesticide formulations containing pyrethrins are being used to treat salmonids for infestations of the copepod parasites Lepeophtherius salmonis and Caligus elongatus (sea lice). The acute lethality of one such formulation to four larval stages of the American lobster (Homarus americanus), a species of significant economic importance in eastern Canada, was determined. The formulation tested contained 0.06% pyrethrins and 0.6% piperonyl butoxide (a synergist). Stage I larvae (48-h LC50 = 4.42 microg/liter) were significantly less sensitive than stage II, III, or IV larvae. Stage II larvae (48-h LC50 = 2.72 microg/liter) were significantly less sensitive than Stage III or IV larvae. Stage III and IV larvae were not significantly different in their response to the pyrethrins formulation (48-h LC50 = 1.39 and 0.73 microg/liter, respectively). Most published studies using lobster larvae have reported that the earliest larval stage was the most sensitive to chemicals. The results described here indicate that the earliest larval stage is the least sensitive to the pyrethrins formulation.

Disruption of energy metabolism and smoltification during exposure of juvenile atlantic salmon (Salmo salar) to low pH.

Juvenile Atlantic salmon were held for 76 days at pH 4.7 during the period when the final stages of smoltification normally occur. Control salmon (pH 6.5) had significant increases in weight, length and liver somatic index which were not observed in those held at low pH. Condition factor decreased in both groups but to a significantly greater extent in the low pH group. After 15 days levels of ADP and glucose were higher and AEC, CP and glycogen were lower in muscles of salmon exposed to low pH. These qualitative differences were maintained until the end of the experiment. ATP and total adenylate concentrations in muscle were lower after 62 days of exposure to low pH compared to controls. The levels of ATP, total adenylates, AEC and glucose were consistently higher in livers of salmon exposed to low pH than those of controls. There were no differences in liver concentrations of AMP, CP and glycogen between the two treatments or with time of exposure within each treatment. The results suggest that exposure of juvenile Atlantic salmon to low pH increased gluconeogenesis and decreased food intake to the detriment of growth.

Adenylate energy charge, arginine phosphate and ATPase activity in juvenile Homarus americanus during the molt cycle.

Neither gill nor hepatopancreas exhibited significant differences in Na+, K+-ATPase activity with molt stage. Hepatopancreatic residual ATPase activity was significantly higher (F = 6.273) in post-molt animals; while gill residual ATPase activity exhibited no significant differences. Muscle AEC did not change with molt stage, but levels of ATP (F = 8.050) and ADP (F = 4.130) were significantly higher in premolt (D3 pleopod stage 5.0-5.5) animals; while levels of arginine phosphate (F = 6.981) were significantly higher in post-molt animals. Arginine phosphate/ATP and ATP/ADP ratios were highest in post-molt animals, but were not statistically significant. Although not significant, changes in Na+, K+-ATPase activity and AEC did suggest alterations in: enzyme activity that correlate with known osmotic compensations occurring during the water uptake and hardening/mineralization processes; and energy metabolism which occur during the molt cycle, respectively.

Disulfiram distribution and elimination in the rat after oral and intraperitoneal administration.

35S disulfiram (DSF), 7 mg/kg, was administered as a single dose to rats both orally (p.o.) or intraperitoneally (i.p.). The 35S DSF was rapidly absorbed by either route. Kidney, pancreas, liver, and the gastrointestinal tract exhibited the greatest uptake of radioactivity, while the least was found in brain. Preferential tissue uptake was similar with both routes of administration. Seven percent of the dose was excreted in the feces. Approximately 12% of the dose was eliminated by the breath as CS2. The 35S-DSF was rapidly metabolized to the 35S-diethyldithiocarbamate-glucuronide and 35S inorganic sulfate. Approximately 93% of the radioactivity was accounted for 48 hr after p.o. or i.p. 35S administration.

The stereoselective metabolism of ethylamphetamine with fortified rabbit liver homogenates.

1. The liver enzyme systems of rabbits involved in the oxidative metabolism of ethylamphetamine were shown to be localized in the microsomal fraction. 2. The effect of substrate concentration, incubation period and storage of the microsomal preparations at 4 degrees was investigated. 3. The results indicate the involvement of at least two stereoselective enzyme systems or different conformations of binding of different substrates to the same enzyme system. R-(-)-Ethylamphetamine is the preferred substrate for N-oxidation and dealkylation, whereas the S-(+)-isomer is preferred for deamination. When racemic ethyl amphetamine is metabolized, the enantiomers act as independent compounds and compete for the enzymes. 4. Neither alpha-C- nor N-oxidation is induced by pre-treatment with phenobarbitone or 3-methylcholanthrene.

The identification and quantitation of the major metabolites of ethylamphetamine, produced by rabbit liver microsomal preparations.

Amphetamine (I), 1-phenylpropan-2-ol (III), phenylacetone (V), N-hydroxyethylamphetamine (VII), and alpha-methyl-N-(1'-phenylprop-2'-yl)nitrone (VIII) were obtained as metabolic products from the incubation of ethylamphetamine (II) with fortified male rabbit liver 9000 g supernatant fractions. These metabolites were identified by comparing their t.l.c., g,l.c. and g.l.c.-m.s. behaviour to that of reference compounds. A method for the quantitative analysis of the metabolites in mixtures using g.l.c. techniques is described.