Efficacy of Nile tilapia (Oreochromis niloticus) juveniles and spinosyns bioinsecticides against aquatic stages of Culex pipiens: An experimental study

The mosquito Culex pipiens is the most widely distributed dipteran species in all regions of Egypt and the principal vector of Wuchereria bancrofti and certain arboviruses in human beings. For controlling C. pipiens vector, biological tools (e.g., larvivorous fish and bioinsecticides) are more potent and safer options to the environment, human beings, and beneficial organisms than chemical pesticides. The efficiency of O. niloticus juveniles as predatory fish species and two bioinsecticides, spinosad 24% and spinetoram 12%, was investigated against the C. pipiens developmental stages in the laboratory. The first trial evaluated the predatory efficacy of small-sized O. niloticus (2.1–2.6 cm; 250–315 mg) and large-sized O. niloticus (2.5–3.2 cm; 250–315 mg) against the 3rd larvae and pupae of C. pipiens. This is the first report in Egypt confirming the predation potential of O. niloticus as efficient predatory fish against the immature C. pipiens. Large-sized O. niloticus predated a greater number of 3rd of C. pipiens larvae and pupae than the small-sized ones. Furthermore, the daily consumption of C. pipiens larvae by small- and large-sized O. niloticus was significantly higher than the pupae. The second trial assessed the toxicity efficacy of spinosad 24% and spinetoram 12% against C. pipiens larvae and pupae. The results confirmed that the tested bioinsecticides showed higher potency toward C. pipiens larvae than pupae after exposure for 24 h and 48 h. Spinosad was more toxic toward 3rd C. pipiens larvae (LC₅₀ = 0.013 and 0.003 mg/L) and pupae (LC₅₀ = 320.69 and 44.28 mg/L) than spinetoram after 24 and 48 h. Herein, O. niloticus juveniles (as promising native predatory fish) and spinosyns bioinsecticides were more effective against C. pipiens in the larval stage than in the pupal stage. In conclusion, Nile tilapia juveniles and biorational compounds, spinosad 24% and spinetoram 12%, might be considered as promising and favorable environmental biological agents for controlling C. pipiens in Egypt. However, further trials are needed to investigate the potential of these agents in the control of this mosquito vector under field conditions.     

Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7–9, 10–12 or 13–15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study.None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females.However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13–15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed.The results of this study have important implications for the widespread use of this drug.     

Morphological description and phylogenetic assessment of 28S rRNA for Thelandros chalcidiae sp. nov. from Chalcides ocellatus

Molecular Biology Reports - Thelandros is a genus of oxyurid nematodes which parasitize both omnivorous and herbivorous hosts. Thelandros chalcidiae sp. nov. is a new taxa described from the large...     

Comparative efficacy and bioavailability of different praziquantel brands

This study investigates the efficacy, bioavailability and drug metabolizing enzymes mainly involved in the metabolism of the commercial brands of praziquantel (PZQ) in Egypt in comparison with the original pure powder. Mice infected with PZQ-susceptible (CD) or PZQ-insusceptible (EE2) Schistosoma mansoni isolates were divided each into seven groups, six of them received PZQ brands (Distocide, Epiquantel, Biltricide, Bilharzid, Praziquantel, and pure PZQ), while the seventh one was left as infected untreated. Seven weeks post-infection, worms were quantified and hepatic CYP450 and CYT b5 were examined. For PZQ pharmacokinetics, groups of normal mice were given the different PZQ brands and divided into subgroups, killed at 2, 5, 15, 30, 60, 90, 120,150, 180, 240 and 360 min post-dosing. Physicochemical examination revealed better dissolution rates for Biltricide, Distocide and PZQ T3A rather than Epiquantel and Bilharzid. Significant decrease in worm burden was recorded in all groups of mice regardless of the brand of PZQ used, but with better results obtained with CD isolate rather than the EE2 isolate. Biltricide and Distocide showed higher C_max and AUC_0–6h in normal mice, in addition to higher worm reduction with least inhibition of CYP450 and CYT b5 in EE2-infected mice. PZQ T3A, Bilharzid and Epiquantel showed, in addition to lower efficacy, higher K_el, lower t_1/2e, C_max and AUC_0–6h. The 32–46% reduction of their bioavailability reflected on their antischistosomal efficacy and recovery of drug metabolizing enzymes. Quality of generic PZQ should include, in addition to examining the physicochemical characteristics of the brands, biological testing including efficacy and bioavailability studies.     

Pharmacodynamics of mefloquine and praziquantel combination therapy in mice harbouring juvenile and adult Schistosoma mansoni

Praziquantel (PZQ) is currently the only drug widely used for the treatment of schistosomiasis, but the antimalarial drug mefloquine (Mef) possesses interesting antischistosomal properties. Combination therapy with these two drugs has been suggested as a strategy for transmission control, as PZQ is active against adult worms and Mef is active against schistosomula. To examine the efficacy of combination therapy, Schistosoma mansoni-reinfected mice were separated into seven groups: untreated (I), treated with PZQ in doses of 200 mg/kg (II) or 1,000 mg/kg (III), treated with Mef in doses of 200 mg/kg (IV) or 400 mg/kg (V); each dose was divided equally and given on two consecutive days. Group VI was treated with doses of PZQ + Mef as in groups II and IV, respectively, while group VII was treated with PZQ + Mef as in groups III and V, respectively. PZQ + Mef at the reduced doses of 200 mg/kg each enhanced the therapeutic efficacy over the reduced PZQ dose alone as shown by a very high reduction in the total numbers of mature worms (95% vs. 49%), immature worms (96% vs. 29%) and the complete eradication of immature females, mature females and immature eggs. The reduction in worm burden was associated with the healing of hepatic granulomatous lesions and the normalisation of all liver enzymes. Therefore, the use of Mef with PZQ is more effective than PZQ alone and should be considered for clinical trials in humans as a potential treatment regimen to prevent treatment failures in areas with high rates of schistosomiasis.     

circRNAs (hsa_circ_00156, hsa_circ _000224, and hsa_circ _000520) are novel potential biomarkers in hepatocellular carcinoma

Circular RNAs (circRNAs) are a newly validated type of noncoding RNAs recently found to be deregulated in several human cancers. More accurate and specific noninvasive biomarkers are strongly needed for better diagnosis and prognosis of hepatocellular carcinoma (HCC). We performed a bioinformatics analysis to retrieve a novel panel of circRNAs potentially relevant to HCC. We examined their expression in the sera of 68 patients with HCC, 60 patients with chronic hepatitis C, and 36 healthy controls using quantitative polymerase chain reaction. We examined the performance characteristics of the selected circRNA biomarker panel in comparison with alpha-fetoprotein (AFP). In addition, we performed a survival analysis to correlate between their expression levels and patient survival. The circRNAs hsa_circ _00224 and hsa_circ _00520 showed a strong biomarker potential with relatively high sensitivities and specificities compared with AFP. The combined panel including the three circRNAs showed superior performance characteristics relative to those of AFP. The median follow-up period was 26 months. hsa_circ_00520 expression has been shown to be associated with relapse-free survival (P < 0.005). circRNAs hsa_circ_00156, hsa_circ_000224, and hsa_circ_000520 are novel potential biomarkers of high sensitivity and specificity, which could potentially be used in the diagnosis of HCC.     

Simultaneous determination of metolazone and losartan potassium in their binary mixtures using high‐performance liquid chromatography with fluorimetric detection: application to combined tablets and spiked human plasma

A new, specific and sensitive reversed‐phase high‐performance liquid chromatography method was developed for the simultaneous determination of metolazone (MET) and losartan potassium (LOS). Good chromatographic separation was achieved within 6.0 min on a 150 × 4.6 mm i.d., 5 µm Waters, Ireland and ProDIGY 5 ODS 3 100 A column. A mobile phase containing a mixture of methanol and 0.02 M phosphate buffer (65:35, v/v) at pH 3.0 was used. The analysis was performed at a flow rate of 1 mL/min with fluorescence detection at 410 nm after excitation at 230 nm. Aspirin (ASP) was used as an internal standard. The proposed method was rectilinear over 2.0–40.0 (MET) and 40.0–800.0 ng/mL (LOS), with limits of detection of 0.22 and 4.52 ng/mL and limits of quantification of 0.68 and 13.70 ng/mL for MET and LOS, respectively. The method was successfully applied for the simultaneous analysis of the studied drugs in their laboratory‐prepared mixtures, single tablets and co‐formulated tablets. Moreover, the method was applied to an in vitro drug release (dissolution) test. The method was further extended to the determination of LOS in spiked human plasma. Statistical evaluation and comparison of data obtained using the proposed and comparison methods revealed no significant difference between the two methods in addition to good accuracy and precision for the proposed method. Copyright © 2013 John Wiley & Sons, Ltd.     

Biochemical and genetic alterations of oxidant/antioxidant status of the brain in rats treated with dexamethasone: protective roles of melatonin and acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-carnitine

The current study was undertaken to investigate the protective role of melatonin (MEL) and acetyl-l-carnitine (ALC) against dexamethasone (DM)-induced neurotoxicity. Adult female rats (60) were divided into: (1) control group, (2) DM-treated group, (3) MEL-treated group, (4) ALC-treated group, (5) MEL- and DM-treated, and (6) ALC- and DM-treated group. Serum acetylcholinesterase (AchE) activity, malondialdehyde (MDA), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were estimated. Gene expression of the prooxidants (NO synthases NOS-1, NOS-2 and heme oxygenases HO-1, HO-2) and antioxidant enzyme (GST-P1) as well as deoxyribonucleic acid (DNA) fragmentation analysis of brain tissue were investigated. Histological examination of the brain tissue was carried out. DM administration caused significant increase in serum AchE activity, MDA and NO levels accompanied with significant decrease in the antioxidant enzymes activity. Pretreatment with MEL or ALC prior DM has been found to reverse all the former parameters. On the genetic level, DM administration significantly increased the expression level of NOS-1, NOS-2, HO-1, and HO-2 messenger ribonucleic acids (mRNAs) and decreased that GST-P1-mRNA in brain tissue. Also, DM produced DNA fragmentation in brain tissue. Treatment with MEL or ALC prior DM administration tend to normalize the above mentioned parameters. These results were documented by the histological examination of brain tissue. The present study suggests that oxidative stress is involved in the pathogenesis of DM-induced neurotoxicity. The inhibition of oxidative stress via stimulation of the antioxidant enzymes by MEL and ALC pretreatment plays a central protective role in modulation of neurotoxicity induced by DM.