Preliminary assessment of the acute toxicity of malathion in animals

Laboratory studies were conducted to acquire information concerning the acute toxicity of malathion in animals under various conditions of exposure. The responses in rabbits and quail exposed to aerosols generated from technical grade malathion (95%) and approximating an ultra-low volume ground spray were compared with those from a 6% malathion/No. 2 fuel oil mixture simulating a high volume spray. Results indicate that technical grade malathion (95%) as an ultra-low volume spray and at effective insecticidal concentrations in particle sizes having a mass median diameter of about 12 µ is relatively nonhazardous compared to the possible toxic fuel oil effects of a 6% malathion/No. 2 fuel oil mixture with a mass median diameter of 25 µ. Based on blood plasma cholinesterase activity analyses, quail were more sensitive to equivalent malathion exposure concentrations than were rabbits. Oral administration of technical grade malathion to rabbits resulted in reduction of plasma and erythrocyte cholinesterase activity at dosages of 120, 300, and 600 mg/kg with death resulting from 1200 mg/kg.The opinions contained herein are those of the authors and should not be construed as official or reflecting the views of the Department of the Army or the Department of Defense. Mention of proprietary products is for the purpose of identification only and does not imply endorsement by the Department of the Army.The experiments reported herein were conducted according to the Guide for the Care and Use of Laboratory Animals (1972) as prepared by the Committee on Revision of the Guide for Laboratory Animal Facilities and Care, of the Institute of Laboratory Animal Resources, National Research Council.     

Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA.

A vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid (alpha-TEA), induce human breast, prostate, colon, lung, cervical, and endometrial tumor cells in culture to undergo apoptosis but not normal human mammary epithelial cells, immortalized, nontumorigenic breast cells, or normal human prostate epithelial cells. Human ovarian and cervical cancer cell lines are exceptions, with alpha-TEA exhibiting greater proapoptotic effects. Although both VES and alpha-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, only alpha-TEA is an effective inducer of apoptosis. VES or alpha-TEA treatment of cp70 cells with 5, 10, or 20 microg/ml for 3 days induced 5, 6, and 19% versus 9, 36, and 71% apoptosis, respectively. Colony formation data provide additional evidence that cp70 cells are more sensitive to growth inhibition by alpha-TEA than VES. Differences in stability of the ester-linked succinate moiety of VES versus the ether-linked acetic acid moiety of alpha-TEA were demonstrated by high-performance liquid chromatography analyses that showed alpha-TEA to remain intact, whereas VES was hydrolyzed to the free phenol, RRR-alpha-tocopherol. Pretreatment of cp70 cells with bis-(p-nitrophenyl) phosphate, an esterase inhibitor, before VES treatment, resulted in increased levels of intact VES and apoptosis. Taken together, these data show alpha-TEA to be a potent and stable proapoptotic agent for human ovarian tumor cells and suggest that endogenous ovarian esterases can hydrolyze the succinate moiety of VES, yielding RRR-alpha-tocopherol, an ineffective apoptotic-inducing agent.     

Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women.

PURPOSE: There is considerable evidence that the presence of mouse mammary tumor virus (MMTV)-like gene sequences in human breast cancer is highly associated with human breast carcinoma. Previous studies have found MMTV-like gene sequences in 38% of breast cancer tissue from United States women. The prevalence of these sequences in Australian and Vietnamese women has never been reported. EXPERIMENTAL DESIGN: Using PCR and primers that amplify MMTV-like gene sequences, we tested cancerous and benign breast tissue from Caucasian-Australian, Vietnamese-Australian, and Vietnamese women. RESULTS: MMTV-like gene sequences were amplified in 19 of 45 (42.2%) archival breast cancer biopsy tissues from Caucasian-Australian women, but only 1 of 120 (0.8%) and 0 of 41 breast cancer biopsy tissues from Vietnamese and Vietnamese-Australian women, respectively. The same sequences were found in only 2 of 111 (1.8%) and 0 of 60 normal (benign) breast tissue samples from Australian and Vietnamese women, respectively. CONCLUSIONS: MMTV-like gene sequences are found in only some human populations and are rarely found in normal human breast tissue from all populations, suggesting they are not present in the normal human genome and have been acquired.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.      

Effects of conjugated linoleic acid supplementation on blood lipids and adiposity of rats fed diets rich in saturated versus unsaturated fat

Conjugated linoleic acid (CLA) may decrease adiposity and improve blood lipid profiles under some conditions. The goal of this study was to determine the effects of CLA supplementation on blood lipid profiles and adiposity of rats fed a diet containing a primarily saturated fat versus a diet containing a primarily unsaturated fat. Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four diets containing coconut oil, coconut oil with CLA, corn oil or corn oil with CLA. After 28 days, blood was collected and serum concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C), and triacylglycerols (TG) were assessed. Food intake, body weights, and epididymal fat pads were measured. No significant differences (p>0.05) were noted among groups for amount of food consumed, weight gained, food efficiency ratio or serum TG concentrations. TC concentrations were lower (p<0.05) in the CLA-supplemented rats that were fed coconut oil but not those consuming corn oil. Serum HDL-C was lower (p<0.05) in rats consuming corn oil but was not significantly different (p>0.05) for CLA supplemented groups. Epididymal fat pads weighed significantly more (p<0.05) in the coconut oil fed group compared to the corn oil fed group, but there was no significant difference (p>0.05) between the corn oil and coconut oil + CLA group. Overall, this study suggests that CLA is more beneficial for control of blood lipids and adiposity when supplemented to a diet rich in saturated versus unsaturated fat.     

Increased nasal potential difference and amiloride sensitivity in neonates with cystic fibrosis

Patients with cystic fibrosis (CF) have an increased nasal transepithelial potential difference (PD) which reflects increased sodium absorption across epithelium relatively impermeable to chloride. To evaluate nasal epithelial function in neonates with CF, the PD was recorded and the voltage response to superfusion of 10(-5M) amiloride, an inhibitor of sodium transport, measured between a Ringer perfused bridge on the nasal mucosa and a reference electrode in the subcutaneous space. We studied three neonates with CF with meconium ileus and compared the results with those in 24 term healthy neonates, including one obligate heterozygote for CF, and 27 control neonates with disease. All three CF neonates had raised sweat chloride values (mean 100 mEq/L) at 2 months. The CF neonates had higher PDs (-64.0 +/- 8.4 mV) than those in normal (-24.4 +/- 2.0 mV) or control (-25.8 +/- 2.0 mV) neonates. Superfusion with amiloride induced a 72% reduction in PD in the CF neonates as compared with healthy (37.5 +/- 1.0%) and diseased (36.0 +/- 1.3%) neonates. The PD and amiloride response in CF neonates are similar to those in CF infants (2.24 months), older CF children (greater than 6 years), and CF adults (-64.9 +/- 9.3 mV; 77.7 +/- 1.8%, n = 51). These results suggest that (1) nasal epithelial dysfunction is present in patients with CF shortly after birth, and (2) the nasal PD may be a diagnostic adjunct to the sweat test in the early diagnosis of CF.     

Blindness after confinement

Four days after an elective caesarean section, a patient went blind within a few hours, associated with a sudden rise in blood pressure. The blindness, initially thought to be caused by a cerebral infarct, was ultimately diagnosed as a result of posterior reversible leuco-encephalopathy syndrome. This rare syndrome is reviewed.