The intrinsic and extrinsic elements regulating inflammation.

Inflammation is a sophisticated biological tissue response to both extrinsic and intrinsic stimuli. Although the pathological aspects of inflammation are well appreciated, there are still rooms for understanding the physiological functions of the inflammation. Recent studies have focused on mechanisms, context and the role of physiological inflammation. Besides, there have been progress in the comprehension of commensal microbiota, immunometabolism, cancer and intracellular signaling events' roles that impact on the regulation of inflammation. Despite the fact that inflammatory responses are vital through tissue damage, understanding the mechanisms to turn off the finished or unnecessary inflammation is crucial for restoring homeostasis. Inflammation seems to be a smart process that acts like two edges of a sword, meaning that it has both protective and deleterious consequences. Knowing both edges and the regulation processes will help the future understanding and therapy for various diseases.

Measurement of cholinesterase enzyme activity before and after exposure to organophosphate pesticides in farmers of a suburb region of Mazandaran, a northern province of Iran.

INTRODUCTION: Accidental toxicity by organophosphate (OP) agents may occur among farmers during spraying season due to improper use and handling. Plasma cholinesterase (ChE) activity measurement is recommended to monitor the extent of exposure to the OP agent. The aim of the current study was to measure plasma ChE activity before and after exposure with OP pesticides. METHODS: This was a prospective study conducted on 36 farmers working in the farm field. The plasma ChE level was measured before spraying and 2 days and 8 weeks after spraying season and exposure to OP agent. Farmers were observed for clinical signs and symptoms of toxicity after exposure. RESULTS: Vertimac was the most common agent used by farmers followed by diazinon and chlorpyrifos. The plasma ChE level significantly decreased after exposure by over 50%. The level returned to preexposure level after 8 weeks. CONCLUSION: Exposure to OP pesticide is a major concern in the developing countries. More than 50% reduction in the plasma ChE activity after spraying is an alarming message for health-care system and policy makers. Furthermore, workplace evaluation, serial ChE monitoring, and appropriate training and education to exposed individuals would be initial important steps to avoid the toxicity or reduce the severity of poisoning.

Aluminum phosphide poisoning known as rice tablet: A common toxicity in North Iran.

BACKGROUND: Aluminum phosphide (ALP) is a highly effective insecticide and rodenticide used frequently to protect stored grain. Acute poisoning with this compound is common in some countries including India and Iran, and is a serious health problem. AIM: The objective of this study was to survey ALP poisoning locally known as "Rice Tablet" and the outcome in a referral poisoning hospital in Mazandaran province, northern part of Iran. MATERIALS AND METHODS: The study was a cross-sectional study from March 2007 to February 2008. Records of all patients admitted and hospitalized to a referral teaching hospital during the 2 year period were collected. Information including gender, age, cause of toxicity, amount of AIP consumed, route of exposure, time between exposure and hospital admission, signs and symptoms of toxicity at admission, therapeutic intervention, laboratory tests, and outcome were extracted from the patients' notes. Patients who died and survived were compared using appropriate statistical tests. RESULTS: During the two-year period, 102 patients, 46 men and 56 women with mean (±SD) age 28.5 ± 12.4 year were admitted with ALP poisoning. The most common signs and symptoms at admission were nausea (79.4%), vomiting (76.5%), and abdominal pain (31.4%). 41.1% of the patients showed metabolic acidosis. Suicidal intention was the most common cause of poisoning (97%) leading to 19 (18.6%) deaths. Compared with the patients who survived, those who died had taken higher amount of ALP tablet (2.2 ± 2.4 vs. 1.4 ± 1.0, P < 0.05), had poor liver function test (P < 0.0001) and severe metabolic acidosis (pH: 7.17 ± 0.19 vs. 7.33 ± 0.08, P < 0.0001). CONCLUSION: ALP poisoning is a common toxicity in Iran causing high morality. This is a serious health problem in agricultural region where ALP is readily available. Withdrawal of ALP tablet from the market and introduction of safer products as rodenticides and insecticides is recommended.

Renal injury at first presentation as a predictor for poor outcome in severe paracetamol poisoning referred to a liver transplant unit.

BACKGROUND: Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying indices of poor prognosis at first presentation is key to both improving clinical care and determining targets for intervention. Renal failure is a feature of severe paracetamol poisoning. The aim of this study was to investigate the relationship between renal function (serum creatinine, Cr) at first hospital presentation and time of tertiary referral to outcomes in severe paracetamol poisoning. METHODS: This was a retrospective cohort analysis of patients referred to the Scottish Liver Transplant Unit due to paracetamol poisoning between 1992 and 2004. The relation between degree of renal injury and outcomes, including worst prothrombin time, Kings College Hospital Criteria (KCHC) and death were examined. The effects of age, nature (single or multiple) and stated size of overdose, hepatic enzyme induction (gamma-glutamyl transpeptidase, GGT), degree of liver injury (aspartate aminotransferase, prothrombin time), blood pressure and renal injury were assessed. RESULTS: Data from 522 patients were included. Renal impairment (Cr >120 mmol/l) was present in 48.8% of patients with liver injury at time of first presentation. Creatinine at first admission predicted poorer outcome in terms of worse prothrombin time, KCHC and death (p < 0.001). Associated risk factors for renal dysfunction included later presentation, staggered ingestion, increased age, hypotension and elevated GGT at first admission. CONCLUSIONS: Creatinine at first admission appears to be a predictor of poor outcome in paracetamol overdose. A better understanding of mechanisms involved in causing renal dysfunction may offer potential therapeutic targets for improving outcome in this common poisoning.

Effect of acute paracetamol overdose on changes in serum and urine electrolytes.

AIMS: To investigate the effects of acute paracetamol overdose on renal function, serum and urine electrolyte excretion in man. METHODS: Two studies were performed in patients admitted with paracetamol overdose: a retrospective study examining changes in serum electrolytes, and a prospective study evaluating changes in serum and urine electrolytes. A control group with SSRI overdose was included in the prospective study. RESULTS: There was a significant dose-dependent relationship between admission (4 h) paracetamol concentration and fall in serum potassium in the retrospective study (P < 0.01) and a significant positive relationship between serum paracetamol at 4 h and fractional excretion of potassium at 12 h postingestion (P < 0.01) in the prospective study. No changes were seen in the control group. No cases developed renal failure. CONCLUSIONS: Paracetamol overdose is associated with dose-related hypokalaemia, and kaliuresis of short duration (<24 h), suggesting a specific renal effect of paracetamol in overdose perhaps via cyclo-oxygenase inhibition. This effect seems distinct from any nephrotoxic effect of paracetamol.

Liver unit admission following paracetamol overdose with concentrations below current UK treatment thresholds.

BACKGROUND: It has been suggested that current UK thresholds for treating paracetamol overdose should be reduced, following case reports of patients developing fatal liver failure after presenting with paracetamol concentrations below these thresholds. AIM: To determine the frequency of severe liver dysfunction following paracetamol overdose when paracetamol concentrations are below current UK antidote thresholds. DESIGN: Retrospective case note review. METHODS: Details were collected from all patients admitted to liver transplant units in Newcastle and Edinburgh with paracetamol-induced hepatotoxicity. RESULTS: Of 696 patients admitted to the two liver units following paracetamol overdose, 14 presented between 4 and 15 h after overdose with paracetamol concentrations below current UK treatment thresholds (estimated annual population rate 0.15/million person-years). Over the period of study, >100 000 presentations with paracetamol overdose would be expected in the catchment populations for these liver units. DISCUSSION: In view of the rarity of this event, this research does not suggest a need to lower the current thresholds for antidotal treatment.