Sublethal and transgenerational effects of spinetoram on the biological traits of Plutella xylostella (L.) (Lepidoptera: Plutellidae)

Spinetoram, a spinosyn insecticide is used to manage lepidopteran pests, including diamondback moth, Plutella xylostella. In addition to determining the lethal effects, identifying low and/or sublethal effects of an insecticide is crucial to understanding the total impact of an insecticide. We assessed the low lethal and sublethal effects of spinetoram on two successive generations of P. xylostella. The initial bioassay results showed that spinetoram exhibited high toxicity against P. xylostella with an LC₅₀ of 0.114 mg L⁻¹ after 48 h exposure. The low lethal (LC₂₅) and sublethal (LC₁₀) concentrations of spinetoram showed significant reduction in pupation rate, pupal weight and adult emergence. The fecundity of F₁ generation was significantly lower in LC₂₅ (117.85 eggs/female) and LC₁₀ (121.34 eggs/female) treated group than untreated control (145.32 eggs/female). The intrinsic rates of increase (r) was significantly lower (r = 0.1984 day⁻¹) in spinetoram treated P. xylostella F₁ progeny compared to untreated control (r = 0.2394 day⁻¹). Our results suggest that LC₁₀ and LC₂₅ concentration of spinetoram might affect P. xylostella population growth by reducing its survival, development, and reproduction.

     

Effects of oral exposure to the phthalate substitute acetyl tributyl citrate on female reproduction in mice

Acetyl tributyl citrate (ATBC), is a phthalate substitute used in food and medical plastics, cosmetics and toys. Although systemically safe up to 1000 mg kg⁻¹ day⁻¹, its ability to cause reproductive toxicity in females at levels below 50 mg kg⁻¹ day⁻¹ has not been examined. This study evaluated the effects of lower ATBC exposures on female reproduction using mice. Adult CD‐1 females (n = 7–8 per treatment) were dosed orally with tocopherol‐stripped corn oil (vehicle), 5 or 10 mg kg⁻¹ day⁻¹ ATBC daily for 15 days, and then bred with a proven breeder male. ATBC exposure did not alter body weights, estrous cyclicity, and gestational and litter parameters. Relative spleen weight was slightly increased in the 5 mg kg⁻¹ day⁻¹ group. ATBC at 10 mg kg⁻¹ day⁻¹ targeted ovarian follicles and decreased the number of primordial, primary and secondary follicles present in the ovary. These findings suggest that low levels of ATBC may be detrimental to ovarian function, thus, more information is needed to understand better the impact of ATBC on female reproduction. Copyright © 2016 John Wiley & Sons, Ltd.     

Acute and population level toxicity of imidacloprid and fenpyroximate on an important egg parasitoid, Trichogramma cacoeciae (Hymenoptera: Trichogrammatidae)

One focus of integrated pest management (IPM) is the use of biological and chemical control in an optimal way. The availability of selective pesticides is important as is information about both lethal and sublethal effects of pesticides on biocontrol agents. Acute and sublethal effects of imidacloprid and fenpyroximate exposure were studied on adult stage of egg parasitoid Trichogramma cacoeciae Marchal and the emergence rate and life table parameters were determined. The adult wasps were exposed to field recommended concentration (FRC) of the pesticides on glass plates. Field rates of imidacloprid and fenpyroximate caused 100 and 32% adult mortality, respectively. Based on concentration–response experiments, the LC₅₀ values of imidacloprid and fenpyroximate were 6.25 and 1,949 ppm, respectively. The effect of imidacloprid and fenpyroximate on larvae, prepupae and pupae of the parasitoid was tested by exposing parasitized eggs of Sitotroga cerealella Olivier or Cydia pomonella L. to the FRC. Imidacloprid and fenpyroximate reduced adult emergence by 10.7 and 29%, respectively, when S. cerealella eggs were used as the host and 10.9 and 24.9%, respectively, when C. pomonella eggs were used as the host. Population parameters of emerged adults from treated pre-imaginal stages by FRC of the pesticides were also studied. The parameters were longevity and progeny production of emergent adults and also intrinsic rate of increase (r _m ), generation time (T) and doubling time (DT). Longevity and progeny production of the emergent adults was not affected by pesticide exposure in comparison to the control. In addition, none of population parameters such as r _m , T and DT were affected by pesticide exposure. The intrinsic rate of increase for the control, fenpyroximate and imidacloprid exposed populations were 0.388, 0.374, and 0.372 female offspring per female per day, respectively. Overall, results of this study suggest a relative compatibility between fenpyroximate and T. cacoeciae, but imidacloprid showed deleterious effects on adults of the parasitoid.     

Combinatorial effect of genistein and female sex‐steroids on uterine fluid volume and secretion rate and aquaporin (AQP)−1, 2, 5, and 7 expression in the uterus in rats

We hypothesized that genistein can interfere with the regulation of uterine fluid volume, secretion rate and expression of aquaporin in the uterus by female sex‐steroids, i.e., estrogen and progesterone. Therefore, the aims of this study were to investigate changes in these parameters in the presence of genistein and female sex‐steroids. Methods: Female Sprague‐Dawley rats were ovariectomized and received 3‐days estradiol‐17β benzoate (E2) plus genistein (25, 50, or 100 mg kg^?1 day^?1) or 3‐days E2 followed by 3‐days E2 plus progesterone with genistein (25, 50, or 100 mg kg^?1 day^?1). A day after last treatment, uterine fluid secretion rate was determined by in vivo uterine perfusion with rats under anesthesia. Animals were sacrificed and uteri were harvested and subjected for histological analyses. Luminal/outer uterine circumference was determined and distribution of AQP‐1, 2, 5, and 7 in endometrium was visualized by immunofluorescence. Expression of AQP‐1, 2, 5, and 7 proteins and mRNAs were determined by Western blotting and Real‐time PCR respectively. Results: Combined treatment of E2 with high dose genistein (50 and 100 mg kg^?1 day^?1) resulted in significant decrease in uterine fluid volume, secretion rate and expression of AQP‐1, 2, 5, and 7 proteins and mRNAs in uterus (p < 0.05). No significant changes in these parameters were observed when 25 mg kg^?1 day^?1 genistein was given with E2 or when genistein was given with E2 followed by E2 plus progesterone Conclusions: Decreased in uterine fluid volume, secretion rate and AQP‐1, 2, 5, and 7 expression in the uterus by high dose genistein in the presence of E2 could potentially affect female fertility. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 832–844, 2017.     

CCR2 on Peripheral Blood CD14+CD16+ Monocytes Correlates with Neuronal Damage,HIV-Associated Neurocognitive Disorders,and Peripheral HIV DNA: reseeding of CNS reservoirs?

HIV-associated neurocognitive disorders (HAND) occur in ~50% of HIV infected individuals despite combined antiretroviral therapy. Transmigration into the CNS of CD14⁺CD16⁺ monocytes, particularly those that are HIV infected and express increased surface chemokine receptor CCR2, contributes to neuroinflammation and HAND. To examine whether in HIV infected individuals CCR2 on CD14⁺CD16⁺ monocytes serves as a potential peripheral blood biomarker of HAND, we examined a cohort of 45 HIV infected people. We correlated CCR2 on CD14⁺CD16⁺ monocytes with cognitive status, proton magnetic resonance spectroscopy (¹H-MRS) measured neurometabolite levels, and peripheral blood mononuclear cell (PBMC) HIV DNA copies. We determined that CCR2 was increased specifically on CD14⁺CD16⁺ monocytes from people with HAND (median [interquartile range (IQR)]) (63.3 [51.6, 79.0]), compared to those who were not cognitively impaired (38.8 [26.7, 56.4]) or those with neuropsychological impairment due to causes other than HIV (39.8 [30.2, 46.5]). CCR2 was associated with neuronal damage, based on the inverse correlation of CCR2 on CD14⁺CD16⁺ monocytes with total N-Acetyl Aspartate (tNAA)/total Creatine (tCr) (r² = 0.348, p = 0.01) and Glutamine-Glutamate (Glx)/tCr (r² = 0.356, p = 0.01) in the right and left caudate nucleus, respectively. CCR2 on CD14⁺CD16⁺ monocytes also correlated with PBMC HIV DNA copies (ρ = 0.618, p = 0.02) that has previously been associated with HAND. These findings suggest that CCR2 on CD14⁺CD16⁺ monocytes may be a peripheral blood biomarker of HAND, indicative of increased HIV infected CD14⁺CD16⁺ monocyte entry into the CNS that possibly increases the macrophage viral reservoir and contributes to HAND.

     

Exposure to the azo dye Direct blue 15 produces toxic effects on microalgae,cladocerans, and zebrafish embryos

Aquatic pollution caused by dyes has increased together with the growth of activities using colorants such as the textile, leather, food, and agrochemicals industries. Because most popular azo dyes are synthesized from benzidine, a carcinogenic compound, a threat to aquatic biota could be expected. The use of single species for toxicity assessment provides limited data, so a battery of test organisms, including representatives of different trophic levels such as algae, zooplankters, and fish, could undoubtedly provide more information. Therefore, our study was aimed at evaluating the toxic effect of the azo dye Direct blue 15 (DB15) on a battery of bioassays using a primary producer (Pseudokirchneriella subcapitata), a primary consumer (Ceriodaphnia dubia), and a secondary consumer (Danio rerio). P. subcapitata was more sensitive to DB15 (IC₅₀ = 15.99 mg L⁻¹) than C. dubia (LC₅₀: 450 mg L⁻¹). In the algae exposed to DB15, chlorophyll-a and -b were significantly increased, and carotenoids were reduced. The concentrations of protein, carbohydrates, and lipids per cell in P. subcapitata exposed to all DB15 concentrations were significantly higher than that measured in control. At 25 mg L⁻¹ of DB15, survival, total progeny, and the number of released clutches were significantly decreased, and the start of reproduction was delayed in C. dubia. DB15 did not induce lethal or sublethal effects in D. rerio embryos at any of the tested concentrations from 24 to 72 h post-fertilization (hpf), but from 96 to 144 hpf, the larvae exposed to 100 and 500 mg L⁻¹ developed yolk sac edema, curved tail, and skeletal deformations. After 144 hpf, DB15 produced a significant increase in embryos without a heartbeat, as the concentration of dye raised. The textile-used, azo dye DB15, caused toxic effects of different magnitude on microalgae, cladocerans, and zebrafish embryos; for this reason, the discharge of this colorant into waterbodies should be regulated to prevent environmental impacts.

     

Neuropsychological Function and Cerebral Metabolites in HIV-infected Youth

The effects of HIV on brain metabolites and cognitive function are not well understood. Sixteen HIV+youths (15 vertical, 1 transfusion transmissions) receiving combination antiretroviral therapy and 14 age-matched HIV- youths (13–25 years of age) were evaluated with brain two-dimensional (2D) magnetic resonance spectroscopy (MRS) at 3 Tesla (T) and a neuropsychological battery that assessed three cognitive domains (attention/processing speed, psychomotor ability, and executive function). The relationship between brain metabolite ratios and cognitive performance was explored. Compared to HIV- controls, HIV+ subjects had higher sycllo-inositol (Scy)/total creatine (tCr) (+32%, p = 0.016) and higher Scy/total choline (tCho) (+31%, p = 0.018) on 2D-MRS in the right frontal lobe. HIV+ subjects also had higher glutamate (Glu)/tCr (+13%, p = 0.022) and higher Glu/tCho (+15%, p = 0.048) than controls. HIV+ subjects demonstrated poorer attention/processing speed (p = 0.011, d = 1.03) but similar psychomotor and executive function compared to HIV- controls. The attention/processing score also correlated negatively with the ratio of N-acetylaspartate (NAA) to tCr on 2D-MRS (r = −0.75, p = 0.0019) in the HIV- controls, but not in the HIV+ subjects (Fisher’s r-z transformation, p < 0.05). Our results suggest that attention/processing speed is impacted by early HIV infection and is associated with right hemisphere NAA/tCr. Scy and Glu ratios are also potential markers of brain health in chronic, lifelong HIV infection in perinatally infected youths receiving antiretroviral therapy.

     

Spontaneous mutations conferring antibiotic resistance to antitubercular drugs at a range of concentrations in Mycobacterium smegmatis

Mycobacteria populations can undergo mutations in their DNA sequence during replication, which if not repaired would be transferred to future generations. Earlier studies have tackled the estimation of mutation rate in mycobacteria at fixed concentrations. However, in this study, in vitro spontaneous mutations in Mycobacterium smegmatis (Msm) mc²155 (Msm) that confers resistance to some of the most important antitubercular drugs; isoniazid (INH^r), rifampicin (RIF^r), kanamycin (KAN^r) and streptomycin (STR^r) were first determined at several highly lethal concentrations, a few of which have not been previously investigated, in a fluctuation assay. Thereafter, mutation rate was estimated using the most commonly adopted Po method, and estimates were then compared concurrently with the Lea-Coulson method of the median and Ma-Sandri-Sarkar Maximum Likelihood Estimator method available on the Fluctuation AnaLysis CalculatOR (FALCOR). The mutation rates of RIF^r ranged from 9.24 × 10⁻⁸ to 2.18 × 10⁻¹⁰, INH^r 1.2 × 10⁻⁷‑1.20 × 10⁻⁹, STR^r 2.77 × 10⁻⁸‑5.31 × 10⁻⁸ and KAN^r 1.7 × 10⁻⁸ mutations per cell division. Data obtained in this study provide mutation rate estimates to key antitubercular drugs at a range of concentrations while also validating a number of the frequent approaches for estimating mutation rates.     

Marine fatty acids aggravate hepatotoxicity of α-HBCD in juvenile female BALB/c mice

Oily fish, a source of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), may contain persistent organic pollutants (POPs), including α-hexabromocyclododecane (α-HBCD). In experimental studies, marine LC n-3 PUFAs ameliorate fatty liver development while HBCD exposure was found to cause liver fatty acid (FA) changes. The present study investigated interactions of FAs and α-HBCD in juvenile female BALB/c mice using a factorial design. Mice (n = 48) were exposed for 28 days to a low (100 μg*kg body weight (BW)⁻¹*day⁻¹) or high dose (100 mg*kg BW⁻¹*day⁻¹) of α-HBCD in diets with or without LC n-3 PUFAs. High dose α-HBCD affected whole body lipid metabolism leading to changes in body weight and composition, and pathological changes in hepatic histology, which surprisingly were aggravated by dietary LC n-3 PUFAs. Hepatic FA profiling and gene expression analysis indicated that the dietary modulation of the hepatotoxic response to the high dose of α-HBCD was associated with differential effects on FA β-oxidation. Our results suggest that in a juvenile mouse model, marine FAs accentuate hepatotoxic effects of high dose α-HBCD. This highlights that the background diet is a critical variable in the risk assessment of POPs and warrants further investigation of dietary mediated toxicity of food contaminants.     

Impacts of seven insecticides on Cotesia flavipes (Cameron) (Hymenoptera: Braconidae)

The endoparasitoid wasp Cotesia flavipes (Cameron) (Hymenoptera: Braconidae) is inundatively released in Brazilian sugarcane plantations to control the sugarcane borers Diatraea saccharalis (Fabricius) and Diatraea flavipennella (Box) (Lepidoptera: Crambidae). In conjunction with these releases, several synthetic insecticides are used to control the neonate larvae of these pests. We assessed the lethal and transgenerational sublethal effects of seven of these insecticides on C. flavipes. Leaf discs were sprayed at the highest field concentrations of chlorantraniliprole, lambda-cyhalothrin + chlorantraniliprole, chlorfluazuron, triflumuron, lambda-cyhalothrin + thiamethoxam, tebufenozide, and novaluron. Distilled water was used as a negative control. Newly emerged females (24 h old) were placed in Petri dishes containing the treated leaves, and the lethal and transgenerational sublethal effects were assessed for the next two generations. Lambda-cyhalothrin + chlorantraniliprole and lambda-cyhalothrin + thiamethoxam caused 100% mortality of the parasitoid and were highly persistent, causing more than 30% mortality at 30 days after spraying. Chlorantraniliprole, chlorfluazuron, novaluron, and triflumuron did not cause significant mortality compared to the negative control, but did have transgenerational sublethal effects. The length of the tibia of the right posterior leg, used as a growth measurement, was reduced in the progeny (F₁ generation) of exposed female parasitoids. In addition, chlorantraniliprole increased and chlorfluazuron reduced the proportion of females in the F₁ generation, whereas novaluron reduced the proportion of females in the F₂ generation. Overall, only tebufenozide was considered harmless to C. flavipes. The results of this study suggest that lambda-cyhalothrin + chlorantraniliprole and lambda-cyhalothrin + thiamethoxam are harmful to C. flavipes, although field studies are needed to obtain results for actual sugarcane crops.

     

Sublethal effects of imidacloprid on the predatory seven-spot ladybird beetle <Emphasis Type="Italic">Coccinella septempunctata</Emphasis>

The seven-spot ladybird beetle, Coccinella septempunctata, is a major natural enemy of aphids in the field and in greenhouses in China and is part of integrated pest management (IPM). Imidacloprid, a highly efficient insecticide that not only kills aphids at lethal concentrations, but also can cause various sublethal effects in nontarget organisms. To strengthen IPM and its sustainability, it is important assessing possible side effects on natural enemies. When the effects of sublethal concentrations (LC5 and 10%LC5) of imidacloprid on C. septempunctata were evaluated, the adult longevity was shortened by 23.97 and 28.68?%, and the fecundity reduced by 52.81 and 56.09?% compared to control population. In the F₁ generation (i.e., the progeny of the exposed individuals), the juvenile development was slower by 1.44 days and 0.66 days, and the oviposition period was shortened by 10 and 13 days, respectively. The fecundity of the F₁ generation decreased by 17.88, 44.03 and 51.69?% when exposed to 1%LC5, 10%LC5, and LC5, respectively. The results of demographical growth estimates showed that the intrinsic rate of increase (r _m ) and net reproductive rate (R ₀ ) were lower in C. septempunctata populations that had been exposed to sublethal concentrations of imidacloprid. The results emphasize the importance of assessing side effects of low imidacloprid concentrations on such predator species, even at the transgenerational level.     

Differential mRNA expression of acetylcholinesterase in the central nervous system of rats with acute and chronic exposure of sarin & physostigmine

A time‐course study was carried out to measure the acetylcholinesterase (AChE) gene expression in the brain of female rats exposed to different doses of sarin and physostigmine. Short‐term effects were studied with an acute single subcutaneous dose (s.c.) of 80 µg kg^?1 (0.5 × LD₅₀) sarin. Cortex and cerebellum showed a significant decline in AChE mRNA expression at 2.5, 24 and 72 h. Biochemical studies showed that plasma butrylcholinesterase (BChE) and brain AChE activities were significantly decreased at 2.5 h, which came back to near control values by 24 h in both cases. For long‐term chronic studies, three groups of female rats received daily doses of physostigmine (0.1 mg kg^?1 day^?1) intramuscularly (i.m.), sarin (15 µg kg^?1 day^?1) s.c. independently and a combined dose of physostigmine (i.m.) (0.1 mg kg^?1 day^?1) followed by sarin (s.c.) (15 µg kg^?1 day^?1) continuously for 30 days. Differential AChE mRNA levels in cortex and cerebellum of rat brain were observed after 30 days and after a lag period of another 30 days with no further administration. Plasma (BChE) and brain (AChE) showed irregular inhibition profile in biochemical studies at 30 days and returned to control levels after 60 days. The acute single subcutaneous administration of sarin for short‐term as well as chronic long‐term studies showed that AChE inhibition alone does not lead to observed changes in mRNA expression of AChE gene. These observations further suggest that route of administration as well as dose exposure regimen also contributes to the regulation of AChE mRNA expression. Copyright © 2009 John Wiley & Sons, Ltd.     

Gender‐specific histopathological response in guppies Poecilia reticulata exposed to glyphosate or its metabolite aminomethylphosphonic acid

Ecotoxicity of glyphosate (GLY) and its metabolite aminomethylphosphonic acid (AMPA) was investigated in guppies, Poecilia reticulata . We tested the effects of these chemicals on the gills and liver of both male and female guppies using qualitative and quantitative histopathological analyses associated with histopathological condition indexes. Both genders showed similar median lethal concentration (LC₅₀) at 96 h for GLY (68.78 and 70.87 mg l⁻¹) and AMPA (180 and 164.32 mg l⁻¹). However, the histopathological assessment of both fish organs exposed to sublethal concentrations of GLY (35 mg l⁻¹) and AMPA (82 mg l⁻¹) for 96 h showed a tissue‐ and gender‐specific histopathological response. In both exposure assays, fish presented mainly progressive changes, such as proliferation of the interlamellar epithelium, partial and total fusion of secondary lamellae. The liver showed mainly regressive changes, such as steatosis, pyknotic nuclei and high distribution of collagen fibers. Unusually large hepatocytes as degenerated cells were also detected. Histopathological changes in gills were similar for the males and females, but the liver response was different between the genders. The hepatic inflammatory changes were more common in males. The increase in the area of hepatocyte vacuoles is gender dependent with higher values in the male compared to the female guppies exposed to GLY and AMPA. Multiparametric analysis indicated that the male guppies are more sensitive than females, particularly in the presence of AMPA. Our study shows that the histopathological assessment associated with gender‐specific response can be successfully used in ecotoxicological assessment of GLY and the metabolite AMPA. Copyright © 2017 John Wiley & Sons, Ltd.     

Pharmacokinetics and haemodynamic effect of deacetyl diltiazem (M1) in rabbits after a single intravenous administration

Deacetyl diltiazem (M₁) is a major metabolite of the widely used calcium antagonist diltiazem (DTZ). In order to study the pharmacokinetic and haemodynamic effects of this metabolite, M₁ was administered as a single 5 mg kg⁻¹ dose intravenously (iv) to New Zealand white rabbits (n = 5) via a marginal ear vein. Blood samples, blood pressure (SBP and DBP), and heart rate (HR) recordings were obtained from each rabbit up to 8 h, and urine samples for 48 h post-dose. Plasma concentrations of M₁ and its metabolites were determined by HPLC. The results showed that the only quantifiable basic metabolite in the plasma was deacetyl N-monodesmethyl DTZ (M₂). The t_1/2 and AUC of M₁ and M₂ were 2.1±0.5 and 3.0±1.1 h, and 1300±200 and 240±37 ng h mL⁻¹, respectively. The Cl and Cl_r of M₁ were 60±10 and 0.81±0.63 mL min⁻¹ kg⁻¹, respectively. M₁ significantly decreased blood pressure (SBP and DBP) for up to 1 h post-dose (p <0.05), but had no significant effect on the heart rate (p >0.05). The E_max and EC₅₀ as estimated by the inhibitory sigmoidal E_max model were 20±18% 620±310 ng mL⁻¹, respectively for SBP; 20±8.3% and 420±160 ng mL⁻¹ for DBP. © 1998 John Wiley & Sons, Ltd.     

Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water

Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104‐week chronic study, a 2‐week analysis of cell proliferation in the urinary bladder and a medium‐term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104‐week chronic study with 32 male rats per group, no treatment‐related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg⁻¹ body weight day⁻¹). In the promotion study, HRE treatment after N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg⁻¹ body weight day⁻¹), respectively. In the 2‐week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg⁻¹ body weight day⁻¹) caused transient increases in 5‐bromo‐2′‐deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low‐dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd.     

In a Model of Neuroinflammation Designed to Mimic Delirium,Quetiapine Reduces Cortisol Secretion and Preserves Reversal Learning in the Attentional Set Shifting Task

Quetiapine, an atypical antipsychotic medication has lacked pre-clinical validation for its purported benefits in the treatment of delirium. This laboratory investigation examined the effects of quetiapine on the attentional set shifting task (ASST), a measure of cognitive flexibility and executive functioning, in a rodent model of lipopolysaccharide (LPS) mediated neuroinflammation. 19 Sprague Dawley female rats were randomly selected to receive intraperitoneal placebo (N = 5), LPS and placebo (N = 7) or LPS and quetiapine (n = 7) and performed the ASST. We measured trials to criterion, errors, non-locomotion episodes and latency to criterion, serum cortisol and tumor necrosis factor alpha (TNF-α) levels. TNF-α levels were not different between groups at 24 h. Cortisol levels in the LPS + Quetiapine group were reduced compared to LPS + Placebo (P < 0.001) and did not differ from the placebo group (P = 0.15). Analysis between LPS + Quetiapine and LPS + Placebo treated rats demonstrated improvement in the compound discrimination reversal (CD Rev1) (P = 0.016) and the intra-dimensional reversal (ID Rev2) (P = 0.007) discriminations on trials to criterion. LPS + Quetiapine treated rats had fewer errors than LPS + Placebo treated animals in the compound discrimination (CD) (P = 0.007), CD Rev1 (P = 0.005), ID Rev2 (P < 0.001) discriminations. There was no difference in non-locomotion frequency or latency to criterion between the three groups in all discriminations (P > 0.0167). We demonstrated preserved reversal learning, no effect on attentional set shifting and normalized cortisol levels in quetiapine-treated rats in this neuroinflammatory model of delirium. This suggests that quetiapine’s beneficial effects in delirium may be related to the preservation of reversal learning and potential downstream effects related to reduction in cortisol production.

Graphical Abstract

     

Sex-related Differences in Rat Liver Microsomal Enzymes and Their Induction by Doxapram

Abstract— The effects of doxapram on the hepatic microsomal mono-oxygenase system of male and female rats were investigated. Male and female rats were administered doxapram (10–120 mg kg^?1 day^?1, i.p.) for 4 days. In female rats, administration of doxapram (20, 40, 60, 80, 100 and 120 mg kg^?1) elevated the parameters in a dose-dependent manner while doxapram (100 and 120 mg kg^?1) elevated the levels of cytochrome P450 and hexobarbitone hydroxylase in male rats. Doxapram (40 mg kg^?1) caused induction of hepatic drug metabolism typified by an increase of hepatic microsomal cytochrome P450 content and activities of hexobarbitone hydroxylase, benzphetamine N-demethylase and ethylmorphine N-demethylase in female rats, but no change in male rats. These findings were supported by the results of SDS/polyacrylamide-gel electrophoresis. However, 7-ethoxycoumarin O-de-ethylase and arylhydrocarbon hydroxylase activities were significantly increased in male rats. NADPH-cytochrome c reductase and NADH-cytochrome c reductase activities, and cytochrome b₅ content were unaffected in rats of both sexes. The sex-dependent cytochrome P450 species may be selectively sensitive to the action of doxapram.     

Inhibition of ATPase activity in the freshwater fish Labeo rohita (Hamilton) exposed to sodium cyanide

Present study concerns the effect of sodium cyanide on the Indian major carp, Labeo rohita. Fishes were exposed to lethal (0.32?mg/L) and sublethal (0.064?mg/L) concentrations of sodium cyanide. The effect of intoxication was studied on Na⁺K⁺ATPase, Mg⁺²ATPase and Ca²⁺ATPase in various physiological tissues (gill, liver, and muscle) at the end of 1, 2, 3 and 4 days of lethal and 5, 10 and 15 days of sublethal exposure periods. Sodium cyanide induced significant inhibitory effects on the ATPase activity of the fish. Inhibition of the ATPase blocked the active transport system of the gill epithelial as well as chloride cells, and thus altered the osmo-regulatory mechanism of the fish. The value of the measured responses as an indicator of stress caused by water contamination discussed. The results confirm that ATPase levels significantly decreased in treated fish, indicating that ATPases could be used as sensitive and useful biomarkers for cyanide pollution.     

Preliminary results on polybrominated diphenyl ether contamination status in Croatian households and insights into children's exposure

Polybrominated diphenyl ether (PBDE) congeners were analyzed in house dust samples collected in Croatian households. ∑PBDEs ranged between 1.1 ng g⁻¹ dust and 17662.4 ng g⁻¹ dust with BDE-99 being the most dominant congener accounting for approximately 60 %. The estimated daily intake (EDI) for toddlers as the most vulnerable population group ranged from 0.003 to 55.04 and from 0.01 to 110.07 ng kg⁻¹ bw day⁻¹ in the central and worst case scenario, respectively. The EDI calculated for the dominant BDE-99 in the sample with the highest ∑PBDE was in the worst case scenario 68.99 ng kg⁻¹ bw day⁻¹, which was quite close to the reference dose of 100 ng kg⁻¹ bw day⁻¹.     

A LIMITED SAMPLING METHOD FOR THE ESTIMATION OF FLUNARIZINE AREA UNDER THE CURVE (AUC) AND MAXIMUM PLASMA CONCENTRATION (CMAX)

A limited sampling model has been developed for flunarizine following a 30 mg oral dose in epileptic patients who were receiving phenytoin or carbamazepine or both, to estimate the area under the curve (AUC) and maximum plasma concentration (C_max). The model was developed using training data sets from 30, 20, 15, or 10 patients at one or two time points. The equations describing the models for AUC using two time points (3 and 24 h) and C_max for the training data set of 30 subjects were AUC_predicted=11·1 C_{3 h}+121·4 C_{24 h}–157 (r =0·80) C_{max(predicted)}=0·036 AUC+42·9 (r =0·74) The model was validated on 64 patients who received flunarizine orally. The model provided reasonably good estimates for both AUC and C_max. The mean predicted AUC of flunarizine was 1230±717 ng h mL⁻¹, whereas the observed AUC was 1203±900 ng h mL⁻¹. The bias of the prediction was 2% and precision was 28%. The mean predicted C_max of flunarizine was 86±32 ng mL⁻¹ as compared to an observed mean C_max of 90±42 ng mL⁻¹. The bias and precision of the prediction were 4% and 24%, respectively. The method described here may be used to estimate AUC and C_max for flunarizine without detailed pharmacokinetic studies. © 1997 by John Wiley & Sons, Ltd.