An observational study on neurobehavioural effects of acute oxydemeton-methyl (insecticide and acaricide) exposure in rats

Oxydemeton-methyl, an organophosphate insecticide and acaricide produced decrease in the exploratory behaviour and prolongation of barbitone sodium-induced hypnosis after intermittent aerosol spray inhalational exposure for 1 h in rats compared to the saline control group. Further, CD50 +/- S.E.M. value for pentylenetetrazole (PTZ) and CI50 +/- S.E.M. value for electroshock (i.e. the dose of PTZ and intensity of electroshock producing positive seizure response in 50% of rats) were significantly decreased by acute exposure to oxydemeton-methyl compared to that of saline control group. The study has established the central nervous system depressant effect and proconvulsant potential of oxydemeton-methyl which is widely used by the agricultural workers in the form of field spray.     

Dose-Finding Study with Nimodipine: A Selective Central Nervous System Calcium Channel Blocker on Aminophylline Induced Seizure Models in Rats

Nimodipine, a dihydropyridine derivative central nervous system (CNS) selective calcium channel blocker was studied at four different dosage schedules in five different models of seizures in rats. At a dose of 5 mg/kg, i.p. with pretreatment time of 15 min, nimodipine significantly antagonized aminophylline (175 and 200 mg/kg, i.p.), electroshock (150 mA for 0.2 s), pentylenetetrazole (60 and 75 mg/kg, i.p.), aminophylline (100 mg/kg i.p.) + electroshock (66mA for 0.2 s), and aminophylline (100 mg/kg, i.p.) + pentylenetetrazole (40 mg/kg, i.p.) induced seizures in rats. No hemodynamic alteration was observed with this dose of nimodipine. However, 2 mg/kg, i.p. (pretreatment time of 15 min and 30 min) and 5 mg/kg, i.p. (pretreatment time of 30 min) doses of nimodipine failed to demonstrate any significant anticonvulsant effect. The study highlighted the critical role of calcium ion flux into the neurons for the genesis of seizure activity to aminophylline, electroshock, and pentylenetetrazole in rats. Furthermore, the critical dose requirement for nimodipine could be explained on the basis of its short half-life and shorter duration of protection against seizures. Therefore, nimodipine may be tried clinically as an anticonvulsant in patients who are on aminophylline because of bronchial asthma or chronic obstructive pulmonary disease, when such patients have concomitant epilepsy or other seizure prone neurological deficits or are scheduled to undergo electroshock therapy.     

Immediate food hypersensitivity reactions on the first known exposure to the food

We report 8 infants with immediate hypersensitivity reactions to foods (milk, egg, or peanut), occurring at the first-known exposure. Each developed symptoms within the first hour, but these generally settled within 2 hours. Sensitisation to the food concerned was demonstrated by positive immediate allergen skin prick tests in every case. Symptoms experienced included irritability, erythematous rash, urticaria, angio-oedema, vomiting, rhinorrhoea, and cough. Five infants were being followed prospectively and 4 were clinically tolerant of the food by age 16 months. The most likely route of sensitisation was via breast milk. None of the infants experienced similar reactions while being breast fed, suggesting that the reaction was dose dependent. As 5 out of a group of 80 infants being followed prospectively developed an immediate reaction at their first known exposure to a food, this appeared to be a not uncommon presentation of food hypersensitivity in infancy.     

Dielectric Analysis of Phosphorylcholine Head Group Mobility in Egg Lecithin Liposomes

Purpose. A knowledge of the interfacial properties of lecithin underpins our understanding of many of the physicochemical characteristics of drug delivery systems such as liposomes and lecithin stabilized microemulsions. In order to further this understanding, a high frequency dielectric study of the interfacial properties of egg lecithin liposomes was undertaken. Methods. The effect of temperature, lecithin concentration and probe sonication on the interfacial dielectric properties of liposomal suspensions was investigated by high frequency dielectric relaxation spectroscopy between 0.2–6 GHz. Results. The frequency dependent permittivity of each suspension exhibited a dielectric dispersion centred around 100 MHz, corresponding to the relaxation of zwitterionic head groups. The activation energy for head group reorientation was estimated as H = 6.3 kJ mol^–1. There was an increase in extent of inter-head group interactions on increasing the liposome volume fraction, whereas the effect of probe sonication showed that: (i) head groups in both the outer and inner lamellae contribute to the dielectric response; (ii) the head groups may be less restricted in liposomes of high surface curvature with few lamellae; (iii) the high frequency permittivity of the suspension increased on sonication, as a result of a reduction in the amount of (depolarized) interlamellar water following a reduction in the number of lamellae per liposome. Conclusions. Dielectric analysis of the zwitterionic head groups of lecithin therefore provides a means for investigating the surface of lecithin liposomes, and may be used to investigate the effect of drugs and other solutes on membranes.     

Identification of 5-(3-(methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-3H-imidazo[4,5-b]pyridine as novel orally bioavailable and metabolically stable antimalarial compound for further exploration

Malaria continues to be a significant public health problem threatened by the emergence and spread of resistance to artemisinin-based combination therapies and marked half a million deaths in 2016. A new imidazopyridine chemotype has been envisaged through scaffold-hopping approach combined with docking studies for putative-binding interactions with Plasmodium falciparum phosphatidylinositol-4-kinase (PfPI4K) target. The docking results steered to the synthesis of compound 1 [5-(3-(methylsulfonyl)phenyl)-3-(4-(methylsulfonyl)phenyl)-3H-imidazo[4,5-b]pyridine] followed by the in vitro screening for antiplasmodial activity and ADME-PK studies. Combined with potent antimalarial activity of compound 1 (Pf3D7 IC₅₀ = 29 nM) with meager in vitro intrinsic clearance, moderate plasma-protein binding, and acceptable permeability, compound 1 displayed sustained exposure and high oral bioavailability in mice and can thus have the potential as next generation PI4K inhibitor for in vivo studies.     

Studies of nephrotoxicity due to mixed exposure to styrene and toluene

Adult male Sprague-Dawley rats were treated simultaneously with 4 mmol styrene per kg i.p., twice a day at an interval of 4 h, and 10 mmol toluene per kg once a day, 5 days a week for 4 consecutive weeks. After the last day of treatment, the rats were placed in metabolism cages for collection of urines for 24 h and then were sacrificed. Such mixed exposure produced significant increases in the urinary excretion of gamma-glutamyl transpeptidase, glucose and proteins as compared to those with either solvent alone. An increase, but not significant, in the urinary excretion of N-acetyl-beta-D-glucosaminidase was also noticed due to such exposure. Electron microscopic examination of renal cortex 24 h after the mixed exposure showed the appearance of many vacuoles of various sizes surrounded by a single membrane, which were not seen in rats treated with either styrene or toluene alone. Metabolism studies showed only a significant increase in the urinary excretion of hippuric acid due to mixed exposure. These data indicate that under certain conditions, mixed subchronic exposure to styrene and toluene may have the potential to increase further the nephrotoxic response as compared to that of either solvent alone.     

TOXICITY AND BIOACCUMULATION OF NICKEL SULFATE IN SPRAGUE-DAWLEY RATS FOLLOWING 13 WEEKS OF SUBCHRONIC EXPOSURE

Adult male Sprague-Dawley rats were given 0, 0.02, 0.05, and 0.1% nickel sulfate (NiSO4 6H2O) or 0, 44.7, 111.75, and 223.5 mg Ni/L, respectively, in their drinking water for 13 wk. Twenty-four hours following the end of such treatment, all animals survived and no apparent clinical signs of toxicity were noted. The final mean body weights of various nickel sulfate-treated rats were not significantly decreased except for the 0.1% nickel sulfate treated group when compared to those in the control. The absolute and relative organ weights were either increased or decreased or remained unchanged, depending on the organ and the dose of nickel sulfate. Total plasma proteins, plasma albumin and globulins, and plasma glutamic pyruvic transaminase activity were all significantly decreased in 0.1% nickel sulfate-treated rats. Lymphocyte subpopulations (T and B cells) were induced at lower dose levels, but suppressed at the highest (0.1 %) dose group. A significant decrease in urine volume and an increase in BUN were observed at the highest dose group. Biochemical analysis of bronchoalveolar lavage fluid and lung tissue showed some lung damage, whereas no damage to the testis or DNA in liver and kidneys were found. No gross or microscopic changes were seen in any of the various tissues examined. The relative order of bioaccumulation of nickel in different organs of rats when treated at 0.1% nickel sulfate (223.5 mg Ni/L) was kidneys > testes > lung = brain > spleen > heart = liver. But with regard to order of toxicity, both immune and pulmonary systems were found to be very sensitive targets, followed by kidney.