ABSTRACT
Recombinant human Interleukin-2 (rhIL-2) continues to be in therapeutic application for the treatment of melanoma and renal cell carcinoma. A regimen of several, repeated dose, daily intravenous injections for 14 or 28 days duration has been shown to induce mortality prior to scheduled terminal sacrifice of the animals. The conventional study design not only manifests in pre-terminal mortalities but also minimizes the characterization of toxic profile of the molecule. In humans, each intravenous treatment exposure involves two five-day treatment cycles separated by 9 days of rest period. The current 28-day study has been designed with three cycles of treatment and two rest periods, each treatment period comprising 5 days of consecutive treatment with 6 or 7 days of rest period. The study included three dose levels at 10, 20 and 40 times the human dose. Treatment related clinical signs such as reduction in the spontaneous activity of animals, abdominal breathing and scruffy coat were noticed in a few animals treated at mid- or high-dose levels. Treatment induced adverse changes were apparent in platelet counts and plasma activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) at mid- or high-dose levels. Histopathology revealed inflammatory cell infiltrates and/or its associated degenerative/regenerative changes in lung, liver and kidneys. The pharmacodynamic response, increase in white pulp was observed in the spleen, which was also evident in the total leukocyte count (WBC count) with a primary increase in the counts of lymphocytes and eosinophils. At the lowest dose level, which was 10 times the human dose, there were no manifestations of major adverse toxicity.
ABSTRACT
The presence of organophosphorus pesticides and heavy metals as food contaminants along the food production line is a common finding. To investigate the interactive/combination effects of chlorpyrifos (CPF) and lead acetate (LA) on biochemical parameters, Wistar rats were exposed to both via dietary mode for a period of 90 days. The study was designed using two different dose levels of CPF and LA, and grouped into seven groups: control - 0 (Group 1), CPF - 1 (Group 2), LA - 50 (Group 3), CPF - 1 + LA - 50 (Group 4), CPF - 10 (group 5), LA 1000 (Group 6) and CPF - 10 + LA - 500 (Group 7) ppm. The haematology and clinical chemistry parameters were evaluated at the end of weeks 4 and 13 of exposure period, and after 4 weeks of recovery period. There were no significant changes in haematological parameters, except for a slight anaemic effect in leadtreated animals. Serum biochemistry revealed reductions in serum and RBC cholinesterase enzymes at the end of weeks 4 and 13 in groups 5 and 7. The 90-day exposure followed by a post-treatment free period of 28-days revealed higher inhibition of RBC cholinesterase enzyme in the recovery group of Chlorpyrifos-plus-Lead treated group, when compared with CPF-alone treated group. A similar trend was observed in serum glucose level of animals treated with a combination of CPF and lead after the treatment-free period of 28 days. The cholinesterase activity and serum glucose concentration observed in group 7 animals were not comparable to group 5 animals after 28 days of recovery period. The findings suggest long lasting and/or persistence of effects of a combination of chlorpyrifos and lead on glucose homeostasis and cholinesterase activity.
ABSTRACT
Primary Foetal Hydrothorax (PFHT), is an intrathoracic collection of fluid in the fetus, which may be present on either side or even bilaterally. Advances in foetal diagnostics now allow consideration of the Ex-utero Intrapartum Treatment (EXIT) procedure for PFHT. Ex-utero Intrapartum Treatment (EXIT) allows therapeutic interventions on the neonate while maintaining fetoplacental circulation and thereby maintaining oxygenation. We report two cases of bilateral PFHT managed successfully with EXIT procedure.
Subject(s)
Adult , Cesarean Section , Female , Fetal Diseases/surgery , Gestational Age , Humans , Hydrothorax/surgery , Obstetric Surgical Procedures/methods , Pregnancy , Pregnancy Trimester, ThirdABSTRACT
Chlorpyrifos, a well known organophosphorus insecticide, and the heavy metal lead, were evaluated for their simultaneous interactive effects on neurobehavioural parameters in Wistar rats after single dose exposure via oral gavaging. The study comprised of functional observation battery and motor activity tests. The study was designed using two different dose levels of chlorpyrifos and lead acetate and grouped into seven groups; control (group 1), chlorpyrifos-5mg/kg (group 2), lead acetate- 100mg/kg (group 3), chlorpyrifos-5mg/kg + lead acetate- 100mg/kg (group 4), chlorpyrifos-50mg/kg (group 5), lead acetate-1000mg/kg (group 6) and chlorpyrifos-50mg/kg + lead acetate-1000mg/kg (group 7). Excitotoxicity and motor activity changes were evident in groups 5 and 7 animals. The animals treated with chlorpyrifos at 50mg/kg exhibited behavioural changes after 2–3 hours of oral gavaging and waned over 2 days. At 50mg/kg chlorpyrifos + 1000mg/kg lead acetate, severe cholinergic signs were noticed approximately 24 hours of exposure and symptoms regressed over 4 days. The incidence and severity of cholinergic behavioural changes were more pronounced in group 7 animals. Chlorpyrifos in the presence of lead delays the cholinergic effects which might be due to its chelating properties with metals and predominant behavioural changes suggest potentiating role of lead on excitotoxicity of chlopyrifos. The present study will be potentially relevant for physicians/scientists to decipher more about variability of action that could arise from accidental poisoning by these agents.