Glyphosate-surfactant herbicide-induced reversible encephalopathy.

Glyphosate-surfactant (GlySH) is a commonly used herbicide that has been used in attempted suicide. Most reports of GlySH toxicity in patients have followed ingestion of the commercial product "Round-up" (Monsanto Ltd; Melbourne, Victoria, Australia), which consists of a mixture of glyphosate (as a isopropylanine salt) and a surfactant (polyoxyethyleneamine). Ingestion of Round-up is reported to cause significant toxicity including nausea, vomiting, oral and abdominal pain. Renal and hepatic impairment and pulmonary oedema may also occur. Impaired consciousness and encephalopathy have been reported as sequelae but there are limited data on the central nervous system (CNS) effects of Round-up toxicity. We report a 71-year-old male who attempted suicide with GlySH and developed a prolonged but reversible encephalopathy suggestive of acute CNS toxicity.

Oviposition responses of Aedes aegypti and Aedes albopictus to certain fatty acid esters.

Laboratory studies were carried out to observe the oviposition responses of Aedes aegypti (L.) and Aedes albopictus (Skuse) to several C21 fatty acid esters. The oviposition activity of these dengue and chikungunya vectors to the long-chain fatty acid esters of C21 length have not been reported earlier. From the multiple choice experiments on oviposition activity in standard mosquito cages, it was observed that compounds hexadecyl pentanoate, tetradecyl heptanoate and tridecyl octanoate presented significant oviposition repellent activity against the two mosquito species, while one compound propyl octadecanoate was found to attract A. aegypti to the treated oviposition substrate at 1- and 10-ppm concentrations. The possible utilization of these esters in integrated vector management is discussed.

Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous route.

Sulfur mustard (SM), chemically bis (2-chloroethyl) sulfide is a bifunctional alkylating agent that causes serious blisters on contact with human skin. Although several antidotes have been reported for the systemic toxicity of SM in experimental animals none of them are approved so far and decontamination of SM immediately by physical or chemical means is recommended as the best protection. Two compounds amifostine [S-2(3-aminopropylamino) ethyl phosphorothioate] and DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulfide] gave very good protection as an oral prophylactic agent against SM the in mouse model, but in the rat model the protection was only moderate. In the search for more effective and less toxic compounds, a number of analogues of DRDE-07 were synthesised and their protective efficacy was evaluated in mouse and rat models. The LD50 of S-aryl substitution was between 1 and 2 g kg(-1) and S-alkyl substitution was more than 2 g kg(-1). In the mouse model, DRDE-07, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 gave about 20 fold protection, and DRDE-23 and DRDE-38 gave less protection of 4.8 and 9.0 fold respectively, against percutaneously administered SM. In the rat model, DRDE-07, DRDE-09, DRDE-10 and DRDE-21 gave about two fold protection. Percutaneously administered SM (19.33 mg kg(-1)) significantly depleted the hepatic GSH content in mice. Pretreatment with DRDE-21 significantly elevated the levels. A 4.4 fold increase in % DNA fragmentation was observed 7 days after SM administration (19.33 mg kg(-1)) in mice. Pretreatment with DRDE-07, DRDE-09, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 significantly protected the mice from SM induced DNA damage. The histopathological lesions in liver and spleen induced by percutaneously administered SM was reduced by pretreatment with DRDE-07, DRDE-09, DRDE-10 and DRDE-21. These analogues may prove as prototypes for the designing of more effective prophylactic drug for SM.

Prophylactic efficacy of amifostine and its analogues against sulphur mustard toxicity.

The successful implication of the chemical weapons convention stimulated research with a new vigour on the destruction of the stockpiled sulphur mustard (SM). A prophylactic agent for SM will be very useful for personnel engaged in the destruction of SM and during inspections by the Organisation for the Prohibition of Chemical Weapons. Due to simple method of preparation, SM can be used clandestinely during war or by terrorist groups. Inspite of research over several decades no satisfactory prophylactic or treatment regimen has evolved for SM. Amifostine an organophosphorothioate, originally developed as a radioprotector, and its analogues were evaluated as a prophylactic agent for SM. Three analogues by varying the chain length and substitution at the sulphur atom were synthesised and coded as DRDE-06, DRDE-07 and DRDE-08. LD(50) of amifostine and its analogues were estimated through intraperitoneal (i.p.) route. For the protection studies, amifostine and its analogues were administered i.p. in mice, 30 min before dermal (percutaneous) application of SM. The dose of the prophylactic agent was 0.2 LD(50) (i.p.) and that of SM was 152 mg/kg (undiluted) equal to 19-fold LD(50) of SM. Amifostine and one of its analogues, DRDE-07 gave significant protection. Further studies were carried out using amifostine and DRDE-07, and both of them significantly protected mice against SM (155 mg/kg, in PEG 300, equal to 19 LD(50)) when they were administered i.p. either 30 min before or simultaneously. LD(50) of amifostine and DRDE-07 were also estimated through the oral route (1049 or 1248 mg/kg, respectively). Prophylactically administered amifostine and DRDE-07 (0.2 LD(50), p.o.) significantly protected the mice against dermally applied SM (155 mg/kg, in PEG 300, equal to 19 LD(50)). The protection offered by DRDE-07 was better than that of amifostine by the oral route. DRDE-07 (0.2 LD(50), p.o.) also protected significantly with respect to the decrease in body weight and the depletion of GSH induced by SM. DNA damage induced by SM was also significantly reduced by amifostine and DRDE-07 (0.2 LD(50), p.o.). Further studies are in progress on the various pharmacological and toxicological properties of DRDE-07.

Effect of inhaled aerosol of 1-chloroacetophenone (CN) and Dibenz (b,f)-1,4 oxazepine (CR) on lung mechanics and pulmonary surfactants in rats.

Inhalation toxicity following exposure to 1-Chloroacetophenone (CN) and Dibenz(b,f)-1,4 oxazepine (CR) aerosols for 60 min at sublethal concentrations were studied in rats. The dynamic surface tension (gamma max and stability ratio) of lung homogenate increased significantly on CN exposure. The lung mechanics studies revealed a significant increase in compliance in CN exposed rats. CR, on the other hand did not influence any of the above variables except for a decrease in compliance. Total lung phospholipids and sphingomyelin contents decreased significantly following exposure to CN, while CR exposure produced an increase in sphingomyelin, reduction in phosphatidylcholine and ethanolamine, with no change in total phospholipid contents. Histomorphological observations indicated cellular degeneration in the epithelium of the bronchiole and alveolar septal-wall thickening due to the presence of an increased number of mononuclear cells in CN exposed rats. However, CR induced inflammatory reaction and enlargement of respiratory air spaces. It is concluded that of the two sensory irritants (tear gases) examined, CN is potentially more toxic compared to CR in rats.

Solid-phase extraction and reversed-phase high-performance liquid chromatographic determination of sulphur mustard in blood.

A reversed-phase high-performance liquid chromatographic method is reported for the analysis of sulphur mustard in blood with the aid of solid-phase extraction sample preparation. Sulphur mustard is extracted from blood samples (both in vitro and in vivo) of rats with a solution of 0.05 M sodium dodecyl sulphate and pre-concentrated over Sep-Pak C18 cartridges pre-coated with Tween-20. A Polygosil C18 column is used with acetonitrile-water (52:48, v/v) as mobile phase for separation and sulphur mustard was detected at 200 nm.

Degradation of bacteriophage lambda deoxyribonucleic acid in vitro by sulfur mustard.

The degradation of bacteriophage lambda (lambda) deoxyribonucleic acid (DNA) by interaction with 0.1, 0.5 and 1 mM concentrations of sulfur mustard (SM) was investigated using agarose gel electrophoresis. Alkaline agarose gel electrophoresis also revealed single strand breaks at 0.5 and 0.1 mM concentrations of SM. The presence of magnesium ions in the reaction mixture prevented DNA degradation. It is proposed that the degradation of lambda DNA by its interaction with an excess of SM may be caused by the breakage of phosphodiester backbone of DNA via the formation of an intermediate phosphotriester bond.

Dose dependent effects on lymphoid organs following a single dermal application of sulphur mustard in mice.

The effects of a single dermal application of sublethal doses [15.5, 7.75 and 3.88 mg kg-1] of bis(2-chloroethyl)sulphide [sulphur mustard, SM] on body weight, organ/body weight ratio, haematology, histology and cellularity of spleen and thymus were studied after 7 days, in Balb/c mice. A progressive fall in body weight was noticed from the fifth day onwards after SM treatment. A dose-dependent decrease in the relative weights of spleen, liver and peripheral lymph nodes, and an increase in adrenal weight were also seen. An increase in red blood cell count, packed cell volume and haemoglobin concentration following SM intoxication were also dose dependent. These changes, together with a significant reduction in the cellularity of the spleen and thymus and degenerative histological changes, show that a single sublethal dermal dose of SM can cause considerable dose dependent systemic effects in Balb/c mice.

Serum, CSF, RBC & urinary levels of magnesium & calcium in idiopathic generalised tonic clonic seizures.

Serum, cerebrospinal fluid (CSF) and urinary levels of magnesium and calcium and RBC magnesium levels were studied in 100 patients of idiopathic generalised tonic clonic seizures and 95 healthy controls matched for age and sex. There was a significant reduction in serum, CSF and RBC magnesium levels and a rise in serum and CSF calcium levels in epileptic patients. The 24 h urinary excretion of calcium and magnesium in the epileptics did not differ from controls. Post ictal (within 24 h of seizure) serum and CSF magnesium levels were significantly lower and calcium levels significantly higher as compared to inter ictal levels (4 wk after seizure). There was no correlation between serum magnesium, serum calcium and CSF calcium levels and the frequency, control or duration of fits. Low CSF magnesium levels correlated with increased frequency, poor control and longer duration of fits. Patients with status epilepticus and those in the EEG abnormalities had low CSF magnesium levels.

A comparative study of biochemical changes induced by inhalation of aerosols of o-Chloroacetophenone & Dibenz (b,f)-1,4-oxazepine in rats.

The biochemical changes in blood samples of rats at different intervals after O-Chloroacetophenone (CN) and Dibenz (b,f)-1,4 oxazepine (CR) were studied. After a single subacute (1/10 LC50) exposure, both the compounds induced hyperglycaemia which was abolished within 24 h. The level of plasma urea was unaltered. CR exposed animals did not show any significant changes in plasma GOT, acid and alkaline phosphatase activities at different intervals. However, in CN exposed animals, a significant elevation of the activities of GOT, GPT, acid and alkaline phosphatase was observed at different intervals. All the parameters became normal within seven days after the exposure. Inhalation of CN aerosols can thus lead to tissue damaging effects in rats.

Dermal intoxication of mice with bis(2-chloroethyl)sulphide and the protective effect of flavonoids.

The influence of dermal application of sulphur mustard (SM) on hepatic lipid peroxidation and the protective effect of flavonoids in SM toxicity was investigated. SM applied on the skin of mice (0.25 or 0.5 LD50) depleted glutathione (GSH) in blood and liver. Malondialdehyde (MDA) levels in the liver showed an increase indicating lipid peroxidation. Administration of vitamin E or two flavonoids, gossypin (GN) and hydroxyethyl rutosides (HR) after dermal application of SM did not alter depletion of GSH but did reduce the MDA level significantly. Survival time of mice with 1 LD50 SM applied dermally was increased by GN and HR to a greater extent than by vitamin E or sodium thiosulphate probably due to one or more of the analgesic, anti-inflammatory, antihepatotoxic, antihistaminic, mast cell stabilization, lipid peroxidation inhibitory and free radical scavenging actions of the flavonoids. The present study indicates that dermally applied SM can induce lipid peroxidation and GSH depletion, and flavonoids may be beneficial in reducing the toxicity.

Inhibition of rat brain cytochrome oxidase activity by pyrolysed products of methyl isocyanate.

The effects were studied of methyl isocyanate (MIC) and its thermally degraded products (dMIC) on rat brain cytochrome oxidase activity. Pure MIC did not inhibit brain cytochrome oxidase activity. A significant inhibition of brain cytochrome oxidase activity by dMIC was observed both in vivo and in vitro. The presence of cyanide in pyrolysed products of MIC has also been confirmed by chemical methods.

Rural development--national improvement.

PIP: Rural development should be viewed as the core of any viable strategy for national development in developing countries where an average 2/3 of the population live in rural areas. Rural development is multisectoral, including economic, sociopolitical, environmental, and cultural aspects of rural life. Initially, the focus is on the provision of basic minimum needs in food, shelter, clothing, health, and education, through optimum use and employment of all available resources, including human labor. The development goal is the total development of the human potential. The hierarchy of goals of development may be shown in the form of an inverted pyramid. At the base are basic minimum needs for subsistence whose fulfillment leads to a higher set of sociopolitical needs and ultimately to the goal of total developmentand the release of creative energies of every individual. If development, as outlined, were to benefit the majority of the people then they would have to participate in decision making which affects their lives. This would require that the people mobilize themselves in the people'ssector. The majority can equitably benefit from development only if they are mobilized effectively. Such mobilization requires raising the consciousness of the people concerning their rights and obligations. All development with the twin objectives of growth with equity could be reduced to restructuring the socioeconomic, and hence political relationships. Desinging and implementing an intergrated approach to rural development is the 1st and fundamental issue of rural development management. The commonly accepted goals and objectives of a target group oriented antipoverty development strategy include: higher productivity and growth in gross national product (GNP); equitable distribution of the benefits of development; provision of basic minimum needs for all; gainful employment; participation in development; self reliance or self sustaining growth and development; maintenance of environmental balance. The most challenging task for development managers in developing countries is to mobilize the vast reservoir of surplus human labor and to channel it to productive use. Forest development and management of forest resources is important for rural development for 2 major objectives: to provide firewood, fodder, and other products; and in many areas and particularly in mountainous countries, forest depletion, largely from uncontrolled agricultural expansion, is leading to a loss of environmental protection of the forest, resulting in floods, droughts, erosion, desertification, silation, and loss of agricultural production.^ieng