Effect of administration route of ddt on acute toxicity and on drug biotransformation in various rodents

DDT was administered to the guinea pig, mouse and rat either ig or ip and to the hamster ig in order to investigate variations in the response of hepatic and duodenal drug-metabolizing enzymes to DDT. The intragastric dose (160 mg/kg) was found to produce gastric bleeding and severe tremor in rats and mice but not in other rodents. The hepatic aryl hydrocarbon hydroxylase activity and cytochrome P-450 concentration decreased after the ig administration of DDT to rats, mice and guinea pigs but in hamsters the activity of aryl hydrocarbon hydroxylase and cytochrome P-450 concentration increased 12 hr after the dosage. The aryl hydrocarbon hydroxylase activity decreased also in the duodenal mucosa of the rat after the ig administration of DDT. The ip dose had no effects on the hepatic or duodenal monooxygenase system in 12 hr. The UDPglucuronosyltransferase activity was slightly lowered in hepatic microsomes of the rat and mouse after the ig dose of DDT, but the decrease was more profound when measured afterin vitro trypsin digestion of microsomes. The trypsin digestion activated the hepatic UDPglucuronosyltransferase in all the species studied,i.e., guinea pig, hamster, mouse and rat (3-, 3-, 5-, and 8-fold, respectively). The duodenal UDPglucuronosyltransferase activity was not affected by DDT administration in any of the species studied. The results suggest that the acute toxic effects of DDT are species-dependent and the administration route is important in DDT toxicity. The hydroxylation step in drug metabolism is more sensitive to DDT than the glucuronidation step.Presented at the Third International Congress of Pesticide Chemistry (IUPAC) Helsinki, Finland, 1974.     

The effect of an intramedullary self-reinforced poly-L-lactide (SR-PLLA) implant on growing bone with special reference to fixation properties. An experimental study on growing rabbits.

Polylactic acid (PLA) is a synthetic biodegradable material. The self-reinforced implants made of poly-L-lactic acid (SR-PLLA) were manufactured of biodegradable polymeric matrix reinforced with fibres of the same material. The purpose of this study was to find out the effect of an intramedullary SR-PLLA implant on growing bone and its applicability to the fixation of a femoral shaft osteotomy in a growing rabbit. In seven rabbits 6 weeks of age a SR-PLLA implant 2.0 mm in diameter and 50 mm in length was introduced into the intramedullary cavity of the right femur. A proximal femoral shaft osteotomy of the right femur was made in another ten 6-weeks-old rabbits. After accurate reduction, fixation of the osteotomy was achieved with an intramedullary 2.0 mm by 50 mm SR-PLLA-rod. The follow-up times were 6 and 28 weeks. An intramedullary SR-PLLA-rod neither caused any disturbance of the bone growth nor abnormalities of the peripheral blood cell counts. Solid union of the osteotomy was seen in six weeks after fixation with SR-PLLA implant.     

Wine and resveratrol: mechanisms of cancer prevention?

Low alcohol consumption seems to decrease total mortality and to have beneficial properties on cardiovascular disease; data for cancer are still inconclusive. There is evidence that wine consumption decreases the risk of cancer at several sites, including cancer of upper digestive tract, lung, colon, basal cell carcinoma, and non-Hodgkin lymphoma. The presence of resveratrol, a polyphenol specifically present in red wine, may contribute to these cancer preventive effects. Resveratrol in fact inhibits the metabolic activation of carcinogens, has antioxidant and anti-inflammatory properties, decreases cell proliferation and induces apoptosis. Data on the availability of resveratrol in vivo are however still lacking. Although regular consumption of one or two glasses of wine seems reasonably safe from the health point of view, a recommendation to the general population for low wine consumption is not justified.     

Opioid treatment for radiating cancer pain: oral administration vs. epidural techniques

In order to determine the optimal pain treatment for patients with cancer involvement of the brachial or lumbar nerve plexuses, a prospective comparative study was carried out using peroral opioid therapy (SO), epidural opioid by a conventional tunnelled epidural catheter (CE) or an epidural catheter connected to an implanted injection port (Port). Pain relief, measured by a visual analog scale (VAS), was similar and adequate in every group already after the first 24 h. CNS side-effects were less frequent and the Karnofsky performance grades slightly superior in the epidural groups. Occlusion and catheter disconnection complicated the pain therapy of five epidural port patients. Epidural dislocation occurred three times in the conventional epidural group. One local infection in the CE group and two in the Port group were recorded. However, no signs of epidural infection were seen at autopsy. The results suggest that due to a lower incidence of side-effects, epidural catheter techniques are superior to peroral opioid in treating pain in these patients. However, complete pain relief was not achieved in all patients, suggesting neurogenic, non-nociceptive pain components. Both epidural techniques seem suitable for long-term pain therapy. Technical improvements are needed in the epidural catheter and the port. The long-term epidural catheter does not seem to cause any major changes in the histology of the dura mater or the connective tissue of the epidural space.     

Spontaneous abortions among women employed in the metal industry in Finland

Summary Spontaneous abortions were analyzed among Finnish metal workers between 1973 and 1976. The information on the workers (35,000 women) was obtained from the files of the Union of Metal Workers; information on the abortions was obtained from the Hospital discharge registry of the National Board of Health. Among metal workers 195 spontaneous abortions were recorded. The proportion of spontaneous abortions was 7.82% (spontaneous abortions/pregnancies, rate) and 13.79% (spontaneous abortions/ births, ratio) of which the latter figure was significantly higher (P< 0.05) than the respective one among all Finnish women. Both the rate and the ratio were significantly increased upon joining the Union as analyzed from an agestandardized material. A particular risk industry appeared to be the production of radios, televisions, and their components. An exposure to solder fumes was suggested to explain the increased risk.     

Embryotoxicity of sixteen industrial amines to the chicken embryo

Sixteen amine compounds that are used in the rubber industry, and sodium nitrite, were tested on three-day chicken embryos for embryotoxicity. The parameters measured were: early deaths recorded within two days of injection, late deaths of malformed embryos, late deaths of non-malformed embryos and malformed survivors. The most embryotoxic chemicals were N-phenyl-N'-isopropyl-p-phenylenediamine, N,N,N-triethylethylenediamine, N,N'-dicyclohexyl-p-phenyleneamine and triethylamine, with total effect ED50 values, including deaths and malformations, between 0.11 and 0.90 mumol per egg. The ED50 values for triethylenetetramine, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine, triethanolamine, N-phenyl-2-naphtylamine, aniline and N-nitrosodiphenylamine ranged from 1.1 to 7.0 mumol per egg. Sodium nitrite was the least potent, with an ED50 of 22 mumol per egg. Six chemicals produced no effects. They probably did not reach the embryo. The four most potent chemicals, together with aniline, caused the highest frequencies of malformations.     

Hypolipidemia and peroxisome proliferation induced by phenoxyacetic acid herbicides in rats

Male Wistar rats were treated daily by gavage with two phenoxy herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D)(100-200 mg/kg body wt) and 4-chloro-2-methylphenoxyacetic acid (MCPA) (100-200 mg/kg body wt), and with the chemically different glyphosate N-phosphonomethyl glycine (300 mg/kg body wt) 5 days per week for 2 weeks. A hypolipidemic drug, clofibrate [ethyl-2-(4-chlorophenoxy)-2-methylpropionate], which is structurally related to phenoxy acids, was used as a positive control (200 mg/kg body wt). 2,4-D and MCPA had several effects similar to those of clofibrate: all three compounds induced proliferation of hepatic peroxisomes, decreased serum lipid levels, and increased hepatic carnitine acetyltransferase and catalase activities. 2,4-D and MCPA, but not clofibrate, decreased lipoprotein lipase activity in the adipose tissue to about a third of the control value but did not change the lipoprotein lipase activity in the heart muscle. The data suggest that these compounds cause hypolipidemia not by enhancing the storage of peripheral lipids in adipose tissue but by preferentially increasing lipid utilization in the liver. Glyphosate caused no peroxisome proliferation or hypolipidemia, suggesting that these effects are associated with the structural similarity between phenoxy acid herbicides and clofibrate.