Acute lead poisoning in an infant.

A case of acute lead poisoning in an infant without overt clinical manifestations of encephalopathy is reported for the first time in Oman. The case was diagnosed at Rustaq Hospital on the basis of (i) history by the mother of giving the child a traditional remedy for treating constipation (ii) X-ray of abdomen showing radio-opaque speckles and (iii) detection of high blood lead levels (83.3 µg/dL) at the toxicology laboratory of the poison control centre. The source of lead was confirmed by high content of inorganic lead (20.2%) found in the sample of the traditional remedy (bint al dahab). The blood lead levels significantly decreased, after the intravenous calcium edetate (EDTA) therapy was given to the baby. The case highlights that early detection and treatment of acute lead poisoning in children can prevent morbidity and sequelae associated with encephalopathy. It also indicated the need for awareness and prevention programme for parents on this issue.

Profile of acute poisoning cases presenting to health centres and hospitals in Oman.

A simple pro forma was used for a retrospective study of poisoning cases at 45 health institutions in Oman during January-December 2000. No deaths were recorded among 2009 cases of acute poisoning. A quarter of all cases (55.8% of paediatric cases) were children aged 1-4 years. The largest category (59.5%) was animal bites and stings: 25.4% undiagnosed, 19.7% scorpion stings, 7.6% bee, spider or wasp stings and 6.8% snake bites. Next highest (38.5%) was ingestion of substances: 18.2% pharmaceuticals, 8.2% food and 4.7% household products. Most drug-related cases were due to paracetamol. Suicide attempts were recorded for 6.0%. Collection of poisoning data through a central registry system is needed for the implementation and future assessment of prevention programmes.

Profile of acute poisoning cases presenting to health centres and hospitals in Oman

A simple pro forma was used for a retrospective study of poisoning cases at 45 health institutions in Oman during January-December 2000. No deaths were recorded among 2009 cases of acute poisoning. A quarter of all cases [55.8% of paediatric cases] were children aged 1-4 years. The largest category [59.5%] was animal bites and stings: 25.4% undiagnosed, 19.7% scorpion stings, 7.6% bee, spider or wasp stings and 6.8% snake bites. Next highest [38.5%] was ingestion of substances: 18.2% pharmaceuticals, 8.2% food and 4.7% household products. Most drug-related cases were due to paracetamol. Suicide attempts were recorded for 6.0%. Collection of poisoning data through a central registry system is needed for the implementation and future assessment of prevention programmes

Cholinesterase inhibition by aluminium phosphide poisoning in rats and effects of atropine and pralidoxime chloride.

AIM: To investigate the cholinesterase inhibition and effect of atropine and pralidoxime (PAM) treatment on the survival time in the rat model of aluminium phosphide (AlP) poisoning. METHODS: The rats were treated with AlP (10 mg/kg; 5.55 x LD50; ig) and the survival time was noted. The effect of atropine (1 mg/kg, ip) and PAM (5 mg/kg, ip) was noted on the above. Atropine and PAM were administered 5 min after AlP. Plasma cholinesterase levels were measured spectrophotometrically in the control and AlP treated rats 30 min after administration. RESULTS: Treatment with atropine and PAM increased the survival time by 2.5 fold (1.4 h+/-0.3 h vs 3.4 h+/-2.5 h, P < 0.01) in 9 out of 15 animals and resulted in total survival of the 6 remaining animals. Plasma cholinesterase levels were inhibited by 47 %, (438+/-74) U/L in AlP treated rats as compared to control (840+/-90) U/L (P < 0.01). CONCLUSION: This preliminary study concludes that AlP poisoning causes cholinesterase inhibition and responds to treatment with atropine and PAM.

Effect of N-acetylcysteine and L-NAME on aluminium phosphide induced cardiovascular toxicity in rats.

AIM: To investigate the protective effects of N-acetylcysteine (NAC) and Nomega-Nitro-L-arginine methyl ester (L-NAME) on aluminium phosphide (AlP) poisoning induced hemodynamic changes, myocardial oxygen free radical injury and on survival time in rats. METHODS: AlP (12.5 mg/kg) was administered intragastrically under urethane anaesthesia. The effect of pre- and post-treatment with NAC and L-NAME alone and in combination was studied on haemodynamic parameters [blood pressure (BP), heart rate (HR), and electrocardiogram (ECG)] and biochemical parameters (malonyldialdehyde, catalase, and glutathione peroxidase). RESULTS: AlP caused significant hypotension, tachycardia, ECG abnormalities, and finally marked bradycardia. The mean survival time was (90 +/- 10) min. There was significant increase in myocardial malonyldialdehyde (MDA), and decrease in catalase and glutathione peroxidase (GSH Px) levels. NAC infusion (6.25 mg . kg-1 . min-1, iv for 30 min) caused insignificant hemodynamic and biochemical changes. Pre- and post-treatment of NAC with AlP significantly increased the survival time, stabilized BP, HR, and ECG, decreased MDA and increased GSH Px levels compared to AlP group. L-NAME infusion (1 mg . kg-1 . min-1, iv for 60 min) as such caused significant rise in BP but precipitated ECG abnormalities. Pre- and post-treatment of L-NAME with AlP neither improved the survival time nor the biochemical parameters despite significant rise in BP. Co-administration of both the drugs with AlP worsened the hemodynamic and biochemical parameters with reduction in the survival time as compared to AlP. CONCLUSION: NAC increased the survival time by reducing myocardial oxidative injury whereas L-NAME showed no such protective effects in rats exposed to AlP.

Serum insulin levels in non-obese, non-diabetic Asian Indians with acute coronary and non-coronary events.

Significant insulin resistance and hyperinsulinemia has been observed to be associated with coronary heart disease in epidemiological studies, particularly so in Asian Indians. This study attempted to investigate if hyperinsulinemia accompanies acute cardiovascular events in Asian Indians, and that it is not a metabolic response to acute stress alone. To test this hypothesis, a case-control study was carried out in a tertiary referral hospital in northern India. Group I (n = 19), consisting of non-diabetic, non-hypertensive, non-obese patients presenting with first episode of acute coronary event (first episode of angina or myocardial infarction) were compared with non-diabetic, non-hypertensive, non-obese patients of group II (n = 21) presenting with non-cardiovascular emergencies (severe abdominal pain e.g. uncomplicated ureteric colic or non-specific intestinal colic. Blood was analysed for glycosylated haemoglobin, fructosamine and insulin levels within 24 hours of the acute event. Elevated serum fructosamine was observed in 11 (57.8%) subjects in group I and 9 (42.9%) in group II (p = NS). Glycosylated haemoglobin was 6.8 +/- 0.1 percent in group I versus 5.9 +/- 0.04 percent in group II (p < 0.01). Three out of 11 subjects in group I and 1/9 subjects in group II having elevated serum fructosamine level also had increased glycosylated haemoglobin level. Five (26.3%) subjects in group I and 2 (9.5%) in group II with elevated glycosylated haemoglobin level were excluded from the analysis as these patients might have been diabetic. Mean serum insulin values were significantly higher in group I (161.3 +/- 8.15 micro IU/mL and 17.5 +/- 1.9 micro IU/mL in groups I and II, respectively; p < 0.001). Eleven (57.8%) subjects in group I had insulin values above 100 uIU/ml. The present study indicates that significant hyperinsulinemia accompanies acute cardiovascular events and it is not an acute response to pain or stress hyperglycemia. Markedly high insulin levels observed in these patients may have a potential role in the pathophysiology of acute coronary event, and may be further studied as a possible prognostic marker.

Effect of intra-tracheal instillation and inhalation of silicon dioxide on some biochemical variables in broncho-alveolar lavage fluid and lung histopathology in rats.

In the present study, the bronchial alveolar lavage fluid (BALF) biochemical and lung histopathological changes occurring in response to single large intra-tracheal exposure to silica have been compared to the changes seen after continued chronic exposure via inhalation. Male albino rats (200-250gms) were exposed to silicon dioxide via intratracheal instillation (8mg/0.05ml saline) and whole body inhalation (200mg/m3, 6 hours/day for 2 and 4 weeks) in separate groups . The respective control animals were instilled with normal saline (0.05ml) or exposed to fresh air in simulation chamber for the same duration. BALF was analyzed for total protein, elastase, malondialdehyde (MDA) levels and catalase activity and histopathology of right lung was carried out after 4 weeks post-exposure in intra-tracheal model and after 2 and 4 weeks of exposure in the inhalation model. The levels of total protein, elastase and malondialdehyde (MDA) were significantly elevated, while catalase activity was significantly decreased in the BALF of exposed animals as compared to controls. The histopathological studies of lungs, showed exudates of inflammatory cells, chiefly of macrophages in the alveolar spaces and interstitial septa with multifocal nodular granulomatous lesions. The biochemical findings in BALF of both the models indicate inflammatory changes, lipid peroxidation and fibrosis. However, comparatively lower catalase activity and higher elastase levels in the 4 week inhalationally exposed group than the 4 week post intratracheally exposed group, suggests that these parameters may be affected by acute and chronic exposure and require further confirmation.

Humoral and cell mediated immune response to cadmium in mice.

The effect of 30, 100 and 300 ppm of cadmium chloride (CdCl2) exposure for 35 days on humoral and cell mediated immune response was examined in Swiss Albino mice. Body burden of cadmium in kidney, spleen and liver was determined and histopathology of these organs was also done. Cadmium chloride in doses of 100 and 300 ppm when fed in drinking water caused significant decrease in IgM and IgG titre against sheep red blood cells (SRBC) and a significant decrease in IgG titre against bovine serum albumin (BSA). The delayed type hypersensitivity response to SRBC and splenic T cell proliferation to BSA was also significantly decreased following 100 amd 300 ppm cadmium exposure. Cadmium accumulation in the spleen, liver and kidney was associated with degeneration and inflammatory changes. It is concluded that cadmium causes significant suppression of humoral and cell mediated immune response in mice which could be due to its cytotoxic action on liver, kidney and immune cells.

Methemoglobinemia in aluminium phosphide poisoning in rats.

Aluminium phosphide (AlP) a grain fumigant is the leading cause of intentional poisoning in North India. The mechanisms involved in toxicity are not known and there is no antidote till date. The present study was carried out to investigate the oxygen free radical generation, methemoglobinemia and effect of methylene blue treatment on survival time in rat model of AlP poisoning. AlP (50 mg/kg, intragastric) was administered in one group and the other group received AlP + Methylene Blue (MB) (0.1%, 1 mg/kg/5 min, i.v.). Malonyldialdehyde (MDA) and methemoglobin (MeHb) levels were measured at 10 and 30 min intervals. Blood MDA levels increased at 10 and 30 min after AlP exposure with simultaneous rise in MeHb levels suggesting methemoglobinemia could be due to increased oxygen free radical generation. Methylene blue caused a significant fall in both the parameters with prolongation of survival time. It is concluded that AlP causes methemoglobinemia responding to methylene blue treatment.

Pulmonary histopathology and alteration in cellular pattern of bronchoalveolar lavage fluid in experimental silicosis.

Pathogenesis of silicosis is still being evaluated. Cellular and histopathological changes in lung following acute and chronic exposure of quartz in rats have been investigated. Inbred wistar rats were given single intratracheal injection of quartz (10 mg in 0.05 ml saline) in groups of acute model, and inhalation of quartz (40 mg/m3 with air flow 5 l/hr in a simulation chamber, 6 hr/day) in groups of chronic model. The control groups were exposed to vehicles only. Rats were sacrificed on day 3, 5 and 7 of intratracheal injection and after 2, 4 and 8 weeks of inhalation. Total and differential cell counts (TC and DC) were performed in bronchoalveolar lavage fluid (BALF). Histopathology was done in the lungs. There was significant (P < 0.001) increase in TC and significant (P < 0.001) changes in percentage of inflammatory cell counts on DC in the BALF of silicotic rats. Histopathology showed progressive inflammatory and fibrotic response in quartz exposed lungs in both acute and chronic models. The results indicate duration dependent inflammatory changes in lungs of both the models. Changes in cell counts precede the histopathological changes and may serve as early biological marker for detection of silicosis.

Role of corticosteroids in cadmium induced immunotoxicity.

Cadmium chloride at doses of 30, 100 and 300 ppm was orally fed to swiss albino mice for 35 days and the humoral and cell mediated immunity was studied by measuring the haemagglutination titre and delayed type hypersensitivity response respectively. Further, the blood corticosteroid level was determined in all the groups. Cadmium at doses of 100 and 300 ppm was found to significantly (p < 0.05) suppress both humoral and cellular immunity with simultaneous increase in the level of blood corticosterone and aldosterone. In order to assess whether the suppression of immune response in cadmium exposed mice is mediated by corticosteroids, aminoglutethemide, an adrenal blocker was administered to mice along with cadmium and the immune response was studied. Aminoglutethemide when administered alone caused significant (p < 0.05) stimulation of immunoglobulin level and delayed type hypersensitivity response as compared to cadmium (300 ppm) fed mice. When co-administered with cadmium, the cadmium induced immunosuppression was reversed back to normal. The results of this study indicate the involvement of adrenal hormones in cadmium induced immunosuppression suggesting that cadmium activates the corticosteroid associated immunoregulatory circuit.

Role of nutrition in toxic injury.

The importance of nutrition in protecting the living organism against the potentially lethal effects of reactive oxygen species and toxic environmental chemicals has recently been realized. This new perspective has prompted re-evaluation of the food constituents of human diet from the point of view of their nutritional adequacy, deficiency and toxicity. The biological antioxidant defense system is an integrated array of enzymes, antioxidants and free radical scavengers. These include glutathione reductase, glutathione-s-transferase, glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, superoxide dismutase (SOD) and catalase, together with the antioxidant vitamins C, E and A. The individual components of this system get utilized in various physiological process and for chemoprotection and therefore require replenishment from the diet. Other components of the diet like carbohydrates, proteins and lipids are important for maintaining the levels of various enzymes required in body's defense system providing protection against carcinogens. However, the emerging newer concepts focus on the role of trace elements and other dietary components in antioxidant defense and detoxification mechanisms. Trace elements like Iron, zinc magnesium, selenium, copper, and manganese are some of the elements involved in antioxidant defense mechanisms. Inadequate intake of these nutrients has been associated with ischemic heart disease, arthritis, stroke and cancer, where pathogenic role of free radicals is suggested. Further the importance of diet in the prevention of chemical induced toxicity can not be undetermined. Recent reports on the role of bioflavonoids as antioxidents and their potential use to reduce the risks of coronary heart disease and cancer in human beings have opened a new arena for future research. Induction of the cytochrome P450 isoenzymes by food pyrolysis, mutagens, alcohol and fasting, on the other hand is reported to contribute to chemical toxicity and carcinogenecity. Certain chemicals moieties in the food are mutagenic and carcinogenic.

Hyperinsulinemia in non-obese, non-diabetic subjects with isolated systolic hypertension.

To investigate the inter-relationship of hyperinsulinemia and isolated systolic hypertension, 15 patients with isolated systolic hypertension (Group I) were compared to those having systolic and diastolic hypertension (Group II), and 14 age- and sex-matched controls (Group III). Significantly high triglycerides and total cholesterol were observed in Groups I and II (p < 0.001) and low high-density lipoprotein cholesterol in Group II (p < 0.001), when compared to controls. Significantly high number of patients had impaired glucose tolerance (80%; p = 0.0002 and 60%; p = 0.05) on oral glucose tolerance test in Groups I and II, respectively. Higher blood glucose values were observed in Group I as compared to Group III, at 0, 30, 60 (p < 0.05) and 120 minutes (p < 0.001). Subjects in all the three groups showed fasting normo-insulinemia. At 60 minutes during oral glucose tolerance test, higher insulin levels were seen in Groups I and II as compared to controls (p = NS). Peak insulin levels and area under curve for insulin were higher in Groups I and II as compared to controls (p = NS). The observations of the present study indicate that, similar to systolic and diastolic hypertension, several features of insulin resistance syndrome such as hyperinsulinemia, dyslipidemia and glucose intolerance accompany isolated systolic hypertension.

Biochemical and histopathological changes in respiratory system of rats following exposure to diesel exhaust.

Effect of exposure to diesel exhaust (DE) for different durations was evaluated using histopathological and biochemical parameters in respiratory system of the rats. Animals were exposed to 1 part DE diluted with 5 parts of clean air in a simulation chamber for 15 min/day for 1, 7, 14 and 21 days. After completion of various exposures, biochemical parameters including elastase inhibitory capacity (EIC) and protein content of the bronchial airway lavage (BAL) and histopathological changes along with lung/body weight ratio were assessed. The elastase inhibitory capacity (an index of the protection against destruction of elastin, a lung connective tissue) was maximum at 1 week indicating thereby that the body renders protection against injury by increasing EIC levels in the initial phase. However, protein content in the BALF increased after 1 week and reached maximum at 2 weeks. Histopathological changes followed similar time course of pattern with accumulation of macrophages and protein exudation. Prolonged exposure up to 3 weeks, however was accompanied by chronic inflammatory changes and thickening of alveolar septa and blood vessels. Changes in lung/body weight ratio and suspended particulate matter (SPM) deposited on filters (simulation chamber) correlated well with EIC, protein content in BALF and histopathological changes. The biochemical findings accompanied with chronic structural changes in the lungs of rats following exposure to DE could be relevant to the clinical observation of increased incidence of chronic lung diseases after continued DE exposure.

Paracetamol poisoning in children.

Paracetamol (acetaminophen) has become an antipyretic drug of choice. Due to its widespread use, toxicity secondary to overdose has increased in recent years. Children are especially vulnerable to accidental exposure due to non availability of child proof containers in India. The main clinical features of acute toxicity include anorexia, vomiting, abdominal pain, jaundice, hematuria and metabolic acidoses. Diagnosis is based on history and laboratory findings of acidosis and abnormal liver function tests. N-acetylcysteine is the specific antidote. This article reviews in detail the toxicokinetics, pathophysiology, clinical features and management of paracetamol poisoning in children.

Poisoning in children: Indian scenario.

The retrospective data on childhood poisoning from eight regional hospitals in India has been reviewed. The demographic features and types of poisonings encountered have been compared. The analysis of the data indicated that pediatric poisonings constituted 0.23-3.3% of the total poisoning. The mortality ranged from 0.64-11.6% with highest being from Shimla. Accidental poisoning was common involving 50-90% of children below 5 years of age and males outnumbered the females. Suicidal poisoning was seen after 13 years of age and was due to drugs and household chemicals. One of the hospitals in Delhi recorded a very high incidence (66.6%) of drug poisoning in children. The drugs consumed belonged to phenothiazines, antiepileptics and antipyretics. Iron poisoning was seen in younger children. Kerosene was one of the causes of accidental poisoning at all hospitals except Shimla and rural Maharashtra were probably wood charcoal is widely used. Pesticide poisoning was more prevalent in Punjab and West Bengal whereas plant poisoning was very common in Shimla. Significant number of snake envenomation has been recorded from rural Maharashtra. Other less common accidental poisonings in children included alcohol, corrosives, heavy metals, rodenticides, detergents and disinfectants. Thus various regions in the country showed some variation in types and frequency of childhood poisoning which could be attributed to different geographical and socio-economic background.

Effect of short and long-term exposure to diesel exhaust on sensitivity of guinea pig tracheal preparation to histamine.

Single exposure, to diesel exhaust (1 part exhaust diluted by 5 parts of clean air) reduced EC50 of histamine indicating hyperresponsiveness of the receptors in trachea of exposed guinea pigs. In contrast, following repeated exposure for 7, 14 or 21 days (15 min/day), EC50 was progressively increased indicating the possibility of down-regulated histamine receptors. Further, simultaneous significant increase in histamine levels (bioassayed on guinea pig ileum) in bronchial airway lavage fluid supports the aforementioned hypothesis. The change in lung/body weight ratio and suspended particulate matter deposited on filters followed the same temporal pattern as EC50. The findings are suggestive of differential effects of diesel exhaust on airway depending upon the duration of exposure.

Role and functions of Poisons Information Centre.

The Poisons Information Centre (PIC) is a specialized unit providing information on prevention, early diagnosis and treatment of poisoning and hazard management. Most of the developed and many developing countries have well established poison control centres with poisons information service, patient management facility and analytical laboratory. In India, the National Poisons Information Centre (NPIC) was established in February, 1995 in the Department of Pharmacology at the All India Institute of Medical Sciences, New Delhi. The centre provides toxicological information and advice on the management of poisoned patients adopted to the level of the enquirer. The basis of this service are the databases on poisoning, drug reactions and also the continuous and systematic collection of data from the library. This information service is available round the clock. The PIC has the training responsibility extending to medical and other health professionals and community. The NPIC organized two successive training courses for medical professionals and para professionals at all health levels. Further, NPIC is a participant of INTOX project of IPCS/WHO, receiving regular yearly training on the use of INTOX database. Laboratory service is an essential component of a poisons control programme, providing analytical services on emergency basis to help in diagnosis and management. The NPIC is developing facilities for quick diagnosis of poisoning cases. Toxicovigilance and prevention of poisoning is another major function of PIC. The Centre has prepared manuals and leaflets on prevention and management cards on treatment of various poisonings. Thus the Centre provides a service with considerable health benefits, reducing morbidity and mortality from poisoning and gives significant financial savings to the community.