Effects of DDT on reproduction in multiple generations of beagle dogs

The effects of chronic oral exposure to 1, 5, and 10 mg of technical DDT/kg/day on: 1) age at puberty, length of gestation, fertility, success of pregnancy, litter size, and lactational ability of dams; 2) viability, survival to weaning, sex distribution and growth of pups; and 3) morbidity, mortality, organ/body weight ratios, gross and histologic abnormalities in all animals were studied through three generations of Beagle dogs. There were a total of 135 adult female and 63 adult male dogs in the project which produced 650 pups. There were no statistically significant differences among control and DDT-treated dogs in any of the reproductive variables, with the exception of age at puberty of the females. DDT-treated females had their first estrous cycles 2 to 3 months earlier (P less than .001) than the control dogs. Selected DDT-treated females, held for a second breeding period, had normal anestrous periods between their first and second estrous cycles. There was no effect of DDT on survival, growth, and sex distribution of pups, nor was there any influence on morbidity, mortality, gross or histologic findings in any of the dogs. All organ/body weight ratios were normal, with the possible exception of an increase in liver/body weight ratio in some DDT-treated animals.     

Concanavalin A toxicity: histological studies

Emetine reversibly inhibits protein synthesis in Chinese hamster ovary (CHO) cells. Stable mutants which are 20-80 fold more resistant to the cytotoxic action of the drug can be isolated in a single step at a frequency of about 2-5 X 10(-7). The frequency of such mutants is increased 30-50 fold by ethyl methane sulphonate mutagenesis, and the spontaneous rate of mutation to emetine resistance as measured by Luria-Delbruck fluctuation analyses is 4.9 X 10(-7) mutations per locus per generation. Protein synthesis in extracts of the mutant cells is resistant to the inhibitory action of the emetine, indicating that the molecular lesion in these cells lies in the protein synthesis machinery.     

Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity

OBJECTIVE: To estimate the efficacy and toxicity of typhoid fever vaccines. DESIGN: Meta-analysis of randomised efficacy trials and both randomised and non-randomised toxicity studies of the parenteral whole cell, oral Ty21a, and parenteral Vi vaccines. SUBJECTS: 1,866,951 subjects in 17 efficacy trials; 11,204 subjects in 20 toxicity studies. MAIN OUTCOME MEASURES: Pooled estimates of three year cumulative efficacy, year specific efficacy, and incidence of adverse events. RESULTS: Three year cumulative efficacy was 73% (95% confidence interval 65% to 80%) for two doses of whole cell vaccines (based on seven trials); 51% (35% to 63%) for three doses of Ty21a vaccine (four trials); and 55% (30% to 71%) for one dose of Vi vaccine (one trial). For whole cell and Ty21a vaccines, regimens of fewer doses were less effective. Efficacy was shown to be significant for five years for whole cell vaccines, four years for Ty21a vaccine, and two years for Vi vaccine. Neither the age of vaccine recipient nor the incidence of typhoid fever in the control group (varying from 6 to 810 cases per 100,000 person years) affected the efficacy of the whole cell or Ty21a vaccines. After vaccination, fever occurred in 15.7% (11.5% to 21.2%) of whole cell vaccine recipients, 2.0% (0.7% to 5.3%) of Ty21a vaccine recipients, and 1.1% (0.1% to 12.3%) of Vi vaccine recipients. CONCLUSIONS: Whole cell vaccines are more effective than the Ty21a and Vi vaccines but are more frequently associated with adverse events. Whether the added efficacy of the whole cell vaccines outweighs their toxicity will depend on the setting in which vaccination is used.     

Effects of monensin on the reproduction, health, and milk production of dairy cows

A randomized clinical trial including 1109 cows from 12 Australian dairy herds was used to evaluate the effects of monensin on the health (n = > 686 cows), production (n = 915 cows), and reproduction (n = > 908 cows) of dairy cows. Cows were allocated to a treatment group receiving a slow-release intraruminal bolus containing 32 g of sodium monensin that was administered 40 d before and 50 d following the anticipated calving date or to a control group. Treatment did not significantly alter any reproductive outcome; 54.5% of cows treated with monensin and 58.2% of control cows were pregnant at first service, and days to conception were lower for cows treated with monensin. The hazard rate (0.95) was not significant for these cows. The percentage of cows pregnant was 83.8 for control cows, and days to first estrus (hazard rate = 1.04) and first service (hazard rate = 1.04) were not significantly higher for treated cows. Treatment with monensin did not significantly alter the risk of any disease. The incidence of retained fetal membranes, pyometra, lameness, abortion, and infectious diseases was not significantly lower for cows in the treatment group, and the incidence of mastitis was not significantly higher for cows in the treatment group. Monensin significantly increased milk production by 0.75 L/d per cow and tended to increase milk fat and protein yields but had no significant effect on milk fat or milk protein percentages. Changes in the production of milk and milk constituents were consistent throughout lactation.     

Effects of physostigmine on benzodiazepine toxicity

The interactions between physostigmine and chlordiazepoxide, diazepam, flurazepam were experimentally evaluated in rats and mice by the following test: loss of righting reflex (LRR), acute toxicity, cardiovascular toxicity and EEG pattern. Physostigmine did not modify the duration of LRR produced by chlordiazepoxide. Conversely, the recovery after diazepam was significantly longer. The LD50 of diazepam and chlordiazepoxide were not modified by physostigmine administration, but that of flurazepam was significantly decreased. Heart rate and blood pressure did not change significantly with physostigmine pre-treatment. However, the total lethal dose was lowered for chlordiazepoxide and flurazepam. Only the reversal by physostigmine of the EEG pattern due to benzodiazepines, offers experimental support to the claimed usefulness of physostigmine in benzodiazepine intoxication in humans. Furthermore, the potentiation of flurazepam toxicity must be taken into account in the debate concerning the clinical advantages of physostigmine.     

Effects of sire, dam traits, calf traits, and environment on dystocia and subsequent reproduction of two-year-old heifers

This study examined the hypocholesterolemic effect and hormonal changes resulting from 30 d of supplementation with Vicia faba L. (field bean) flour of diets of young men (aged 18-21 y; n = 40) with borderline-high or high serum cholesterol values. All subjects (groups A-D) consumed the same basic diet. Additionally, volunteers in the control group (A) consumed 90 g control flour/d whereas those in the three bean groups received either 90 g cooked field bean flour (groups B and C) or 90 g raw field bean flour (group D) daily. Groups A and B included volunteers with borderline-high cholesterol values [5.2-6.2 mmol total cholesterol/L and 3.4-4.1 mmol low-density-lipoprotein (LDL) cholesterol/L]. Subjects in groups C and D had high serum cholesterol concentrations (total cholesterol > 6.2 mmol/L and LDL cholesterol > 4.1 mmol/L). After 30 d, serum glucose, insulin, triacylglycerol, total, LDL-cholesterol, and very-low-density-lipoprotein (VLDL)-cholesterol values were significantly lower than initial values in all subjects who consumed diets containing field bean flour (P < or = 0.0001, except for LDL-cholesterol concentrations in group C, for which P < or = 0.0007). Legume intake also resulted in a significant increase (P < or = 0.0001) in glucagon and high-density-lipoprotein cholesterol. Neither cortisol nor thyroid hormone values changed significantly. The results suggest that the hypocholesterolemic effect of field bean intake depends at least partly on a concomitant increase in glucagon and decrease in insulin values. The more marked reduction in triacylglycerol and VLDL-cholesterol concentrations in subjects who consumed raw field beans indicates a coparticipation of their thermolabile components.     

Histopathological studies on the toxicity of ochratoxin A in rats. I. Acute oral toxicity

Traumatic spinal cord lesions in children are infrequent (2 to 5 per cent of all cases admitted to specialised paraplegic centres depending on whether the upper age limit is set at 10 or 15 years). Traffic accidents are responsible for at least 50 per cent of the lesions; playground accidents and various sports add another 35 per cent. A large proportion of the accidents have been found to be related to the child's normal desire for adventure and exploration. The segment most frequently involved in our own series of 18 cases was the cervical and upper thoracic spine. Histopathological studies have shown that splitting of the cartilaginous end-plate in the growth zone of the vertebrae is a common finding. Radiological signs of spinal trauma are less evident than in adults; they may be totally missing. Precise neurological assessment must rely on repeated examination and close clinical observation, especially in the comatous child with a head injury. Spinal cord involvement must be suspected and the child treated as a paraplegic until definite proof of a normal neurological status is available. Due to a highly labile water electrolyte balance in the early post-traumatic stage and considerable fluctuations in plasma volume and temperature regulation, permanent monitoring of the cardiovascular function, body temperature and diuresis is mandatory. In children below the age of 10, deep vein thrombosis and embolism are exceptional (sepsis creates a high-risk situation requiring anticoagulation). In the initial treatment of spinal injury only conservative measures should be considered; there are no indications for laminectomy, nor for spinal fusion. In the tetraplegic child below the age of 6, skull-traction should be avoided and immobilisation of the cervical segment achieved by bilateral padded head-rests.     

Effects of 2-ethylhexanoic acid on reproduction and postnatal development in Wistar rats

Reproductive toxicity of 2-ethylhexanoic acid (2-EHA) was studied in Wistar rats. The animals (24 animals per sex per group) were given 2-EHA as a sodium salt in drinking water at daily doses of 100, 300, or 600 mg/kg. Control animals received plain water. Male rats were exposed to 2-EHA for 10 weeks and females for 2 weeks prior to mating, both sexes during the mating period and females during the entire gestation and lactation period. 2-EHA caused a slight but dose-dependent decrease in fertility; time to mating increased at 300 and 600 mg/kg and even total infertility ensued. 2-EHA slightly decreased sperm quality in males. The spermatozoa were significantly less motile at 100 and 600 mg/kg and abnormal sperm occurred more frequently at the two highest dose levels. The average litter size was reduced by 16% in the dose group receiving 600 mg/kg. The birth weights of the pups were unaffected but the body weight gain was transiently slower during lactation at 600 mg/kg. Several pups appeared abnormal (kinky tail, lethargic, slightly paralyzed legs) and the physical development assessed by several landmarks (opening of eyes, eruption of teeth, hair growth) and reflexes (grip reflex, cliff avoidance) was delayed at 300 and 600 mg/kg. In another experiment, a single dose of 600 mg/kg 2-EHA was given to pregnant females by gavage on Gestational Day 4, 5, 6, or 7 and the number of implantations were counted on Gestational Day 10. Administration on Day 6 decreased the number of implantations and caused resorptions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic toxicity, oncogenicity, and mutagenicity studies with chlorotetrafluoroethane (HCFC-124)

The chronic toxicity, oncogenicity, and mutagenicity of chlorotetrafluoroethane (HCFC-124) were evaluated. In the chronic toxicity/oncogenicity study, male and female rats were exposed to 0, 2000, 10,000, or 50,000 ppm HCFC-124 for 6 hr/day, 5 days/week, for 2 years. Body weights were obtained weekly during the first three months of the study and every other week for the remainder of the study. Food consumption was determined weekly. Clinical signs of toxicity were monitored throughout the study. An ophthalmological examination was performed on all animals prior to study start, and all surviving rats were examined at approximately 3, 12, and 24 months after study start. Clinical pathology was evaluated at 3, 6, 12, 18, and 24 months. An interim termination was conducted at 12 months. All surviving rats were necropsied at 24 months. A complete set of tissues was collected for microscopic examination, and selected tissues were weighed. There were no compound-related, adverse effects on body weight, food consumption, survival, clinical signs of toxicity, ophthalmoscopically observable ocular lesions, serum hormone concentrations, or clinical pathology parameters at any exposure concentration in either male or female rats. Compared to controls, urine fluoride was increased in males and females at all exposure concentrations, and plasma fluoride was increased in females at all exposure concentrations. Excretion of fluoride represents conversion of the parent molecule, and as such is not considered to be an adverse effect. There were no toxicologically significant, compound-related organ weight changes or gross or microscopic findings in male or female rats at any of the exposure concentrations tested. HCFC-124 was not toxic or carcinogenic in rats of either sex after inhalation exposure at concentrations of up to 50,000 ppm in this two-year chronic toxicity/oncogenicity study. After exposure to HCFC-124 for six hours per day, five days per week, for 24 months, the no-observed-adverse-effect level for male and female rats was 50,000 ppm. HCFC-124 was not mutagenic in Salmonella typhimurium strains TA1535, TA97, TA98, and TA100 with and without activation when evaluated at concentrations up to 60% HCFC-124 for 48 hours. No evidence of clastogenic activity was observed in cultured human lymphocytes at atmospheric concentrations up to 100% HCFC-124 for 3 hours, with and without metabolic activation. In vivo, no micronuclei were induced in mouse bone marrow cells following exposure of mice to concentrations of 99,000 ppm HCFC-124 6 hours/day for 2 days.     

Effects of cold stress on survival and reproduction of Haematobia irritans (Diptera: Muscidae)

1. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) increases the stability of the oxazolidine prodrug toward hydrolysis. 2. The binding constant (Kb) and rate constant (Kc) for the hydrolysis of the prodrug-HP-beta-CD complex were calculated from the kinetic data. 3. Ion-spray mass spectra confirmed prodrug-HP-beta-CD complexation. 4. Mass spectral and kinetic data indicated 1:1 stoichiometry for the complex. 5. A significant elevation of locomotor activity in rats was observed when either (-)-ephedrine or the prodrug was administered by either the intraperitoneal or the oral route. 6. Addition of HP-beta-CD potentiated the central nervous system effect of both (-)-ephedrine and the prodrug when administered intraperitoneally. However, when the drugs were administered orally, HP-beta-CD caused a decrease in activity.     

Effects of avermectin residues in cattle dung on dung beetle (Coleoptera: Scarabaeidae) reproduction and survival

Scarabaeine dung beetles feeding on dung from cattle treated with an injection of avermectin at a therapeutic dose to control internal parasites, show larval mortality, mortality of immature adults, reduced egg production, and inhibited ovariole development for periods of 1-4 weeks following treatment. In winter rainfall regions of Australia, feeding by newly emerged adults of an introduced species, Onthophagus binodis, resulted in shredding of cattle dung between December and May. Production of brood masses and eggs resulted in dung being buried from September to November. Feeding by newly emerged adults of a native species, Onthophagus ferox, resulted in dung being buried in May and June, and production of brood masses for breeding resulted in dung burial between September and November. There are thus 2-6 months of the year when injection of cattle with avermectin would affect mortality of newly emerged beetles, and 3 months of the year when avermectin treatment of cattle would affect dung beetle oviposition or larval survival. Beetles were attracted to fresh dung for 2-4 days, and most had left the pad within a week. There are no data to indicate the effects of avermectin residues in dung on dung beetle populations and on beetle fitness. Tests should be done to determine if avermectins in slow release devices have a greater effect on dung beetles than injections, and to determine what effects both have on dung beetle populations.     

The role of xenobiotic metabolizing enzymes in arylamine toxicity and carcinogenesis: functional and localization studies

Familial apolipoprotein C-II (apo C-II) deficiency is an autosomal recessive genetic disorder characterized by fasting hypertriglyceridemia and accumulation of chylomicrons in the plasma. To elucidate the genetic defect, the apo C-II gene of a neonatal Japanese patient (C-IITokyo) was analyzed. Nucleotide sequence analysis showed a G+1 to C transversion at the donor splice site of intron 2 (INT2 G+1 to C). Restriction fragment length polymorphism analyses of the patient's family members with Hph I showed that the patient was homozygous and the parents were heterozygous for the INT2 G+1 to C mutation. Although consanguinity could not be demonstrated, haplotype analysis of the C-II gene revealed the identity of the patient's alleles on the mutation, suggesting that the parents had a common Japanese ancestor. Sequence analysis of the patient's cDNA isolated from peripheral blood lymphocytes revealed that the INT2 G+1 to C mutation causes skipping of exon 2, which encodes the initiation codon, and results in deficiency of apo C-II proteins. The outstanding feature of our patient was that he showed severe hypertriglyceridemia beginning in the neonatal period, a feature not reported in a case of apo C-II deficiency (C-IIHamburg) with the same mutation as our patient. A previous report of another case of apo C-II deficiency (C-IIToronto) suggested that the apo E4 isoform is associated with higher levels of plasma triglycerides in subjects heterozygous for the apo C-II mutation. Determination of the apo E isoform of our patient revealed that apo E4 was coinherited with the INT2 G+1 to C mutation, whereas the apo E isoform has been reported to be E2/3 in C-IIHamburg. We speculate that apo E4/4 aggravated the hypertriglyceridemia in our patient with apo C-II deficiency.