Human & Experimental Toxicology current issue

Studies on hypoglycaemic effects of polyherbal preparation in streptozotocin-induced diabetic male albino rats

Mon, 16 Nov 2009 09:01:18 PST

Many traditional treatments have been recommended in the alternative system of medicine for diabetes mellitus. However, the mode of action of most of the herbals used has not been defined. It has been reported that sex hormones are important regulators of insulin-mediated events in skeletal muscles. In view of this, a novel herbal preparation containing antidiabetic and aphrodisiac plants was used in the present study. Adult male albino rats were divided into following groups after induction of diabetes. Rats were given an intraperitoneal (i.p.) injection of streptozotocin (STZ), at a dose of 65 mg/kg body weight after overnight fasting, to induce diabetic state with blood glucose levels >250 mg/dL. Group 1—Control rats treated with single i.p. injection of vehicle, Group 2—Rats treated with polyherbal preparation (PHP; 500 mg/kg body weight by oral intubation, morning and evening for 30 days), Group 3—STZ-diabetic rats treated orally with equal volumes of vehicle (water) alone and Group 4—STZ-diabetic rats treated with PHP after 10 days of diabetic induction. STZ-diabetes decreased the body weight, serum insulin level and glucose oxidation in liver and skeletal muscles but increased the fasting blood glucose level. After polyherbal treatment, body weight and glucose oxidation were completely restored to control level while serum insulin level was restored partially and the glucose tolerance was significantly improved. There was a significant decrease in total haemoglobin (Hb) level of diabetic rats when compared to control but polyherbal treatment significantly improved the same. However, the other parameters studied (red blood cell [RBC], white blood corpuscle [WBC], packed cell volume [PCV], mean corpuscular volume [MCV] and mean corpuscular haemoglobin [MCH]) were unaltered. In conclusion, the anti-diabetic properties of PHP appear to be mediated through pancreatic β-cell regeneration, resulting in maintenance of optimal blood glucose and its oxidation in liver and skeletal muscles.

Attenuation of Helicteres isora L. bark extracts on streptozotocin-induced alterations in glycogen and carbohydrate metabolism in albino rats

Kumar, G., Sharmila Banu, G., Murugesan, A. — Mon, 16 Nov 2009 09:01:18 PST

The present study was undertaken to assess the effect of Helicteres isora L. on four important enzymes of carbohydrate metabolism (glucokinase [GK], hexokinase [HK] phosphofructokinase [PFK] and fructose-1, 6-bisphosphatase [FBP]) along with glycogen content of insulin-dependent (skeletal muscle and liver) and insulin-independent tissues (kidneys and brain) in streptozotocin (STZ; 60 mg/kg)-induced model of diabetes for 30 days. Administration of bark extracts (100, 200 mg/kg) for 30 days led to decrease in plasma glucose levels by approximately 9.60% and 22.04% and 19.18% and 33.93% on 15th and 30th day, respectively, of the experiment. Liver and two-kidney weight expressed as percentage of body weight significantly increased in diabetics (P < 0.05) versus normal controls. Renal glycogen content increased by 10 folds while hepatic and skeletal muscle glycogen content decreased by 75% and 68% in diabetic controls versus controls. H. isora did not affect glycogen content in any tissue. The decreased activities of PFK, GK, FBP and HK in diabetic controls were 40%, 50%, 50% and 60% and bark extract of H. isora partially corrected this alteration. The efficacy of the bark extract was comparable with Tolbutamide, a well-known hypoglycemic drug.

Spider bite (latrodectism) in Mashhad, Iran

Afshari, R., Khadem-Rezaiyan, M., Balali-Mood, M. — Mon, 16 Nov 2009 09:01:18 PST

Background: Spider (Latrodectus tredecimguttatus) bites are relatively common in North East Iran. They induce morbidity and rarely mortality. We aimed to investigate clinical, electrocardiographic and para-clinical changes in patients with this bite. Methods: All consecutive patients admitted with suspected spider bites between September 2005 and September 2006 were studied prospectively. Results: Spider bites accounted for 56 cases (0.5% of all poisoning, 21% of all admitted envenomated). The patients’ mean (SD) age was 32 (16) years. The most common findings were pain (90%) mainly in their back (45%), stomach (35%), lower limbs (33%), upper limbs (19%) and chest (14%). Other clinical findings included were sweating (55%), chills (29%), dyspnea (25%), flushing (14%), spasm (12%), headache (12%), nausea (12%) and vertigo (12%). On electrocardiograph (ECG); ST segments were depressed in 25% of cases in at least two of the pre-cordial leads. Laboratory findings were in normal ranges. All the patients recovered following supportive and symptomatic treatment (no anti-toxin available in Iran), with a mean hospitalization period of 1.9 (1.3) days. Conclusions: Spider (L. Tredecimguttatus) bite is relatively common in Mashhad, which induces latrodectism with relatively different findings and cardiac toxicity. ECG monitoring should be considered, particularly when specific anti-toxin is not available.

Polybrominated diphenyl ethers cause oxidative stress in human umbilical vein endothelial cells

Kawashiro, Y., Fukata, H., Sato, K., Aburatani, H., Takigami, H., Mori, C. — Mon, 16 Nov 2009 09:01:18 PST

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants to prevent combustion in consumer products, such as electronics, construction materials, and textiles and, therefore, have become important commercial substances. PBDEs were also detected in maternal blood, breast milk, umbilical cord blood, and cord tissue, thereby indicating that fetuses were also exposed to PBDEs. The purpose of this study is to identify the effect of PBDEs on human umbilical vein endothelial cells (HUVECs). Cultured HUVECs were exposed to a commercial mixture of penta-BDE (DE71), octa-BDE (DE79), and deca-BDE (DE83). Each gene expression that was altered in DNA microarray was confirmed by real-time reverse transcription—polymerase chain reaction and Western blotting analysis. The results indicated that gene expressions concerning antioxidant system, i.e., thioredoxin family, 24-dehydrocholesterol reductase (DHCR24), and tumor suppressor protein p53, were altered by PBDEs exposure in HUVECs. Moreover, it was demonstrated that thioredoxin-interacting protein (TXNIP) was a target gene in exposure to DE71 and DE79 in HUVECs, by drastically decreasing time-dependent TXNIP expression in HUVECs.

An atropine and glycopyrrolate combination reduces mortality in organophosphate poisoning

Arendse, R., Irusen, E. — Mon, 16 Nov 2009 09:01:18 PST

Anticholinergics are the mainstay of the pharmacological management of organophosphate poisoning (OPP). Atropine has the potential to cause central toxicity which may complicate the management of this life-threatening condition. A combination of atropine and glycopyrrolate in equivalent dosages titrated to the peripheral muscarinic signs, theoretically reduces the central effect of the anticholinergics by 50% and thereby the risk of central toxicity, while it provides effective control of the peripheral manifestations of OPP. This study reports the clinical morbidity and mortality associated with the management of OP with this anticholinergic combination over a 4-year period, 2003 to 2006, at Tygerberg Academic Hospital (TAH). Two of the 53 patients treated for OPP died, with this mortality lower than that previously reported at TAH. Atropine toxicity was evident in 12 (22.5%) patients and responded to a temporary cessation of the combination infusion. The demographic profile, presenting symptoms, duration of stay and complications encountered were similar to previous reports from TAH. Patients treated with the infusion of a combination of atropine and glycopyrrolate had a lower mortality rate compared with earlier reports from the same unit, but the occurrence of atropine toxicity was unchanged despite the hypothesized theoretical advantage.

Severe scorpion envenomation in children: Management in pediatric intensive care unit

Mon, 16 Nov 2009 09:01:18 PST

Background: Scorpion envenomation is a common public health problem worldwide and children are at greater risk of developing severe cardiac, respiratory and neurological complications. The aim of this study was to evaluate the effects of antivenin and/or prazosin use on prognosis of scorpion-envenomed children admitted to pediatric intensive care unit (PICU). Methods: The standardized medical records of 45 children hospitalized with severe scorpion sting in PICU were retrospectively evaluated. General characteristics of the children, clinical and laboratory findings, treatment approaches and prognosis were evaluated. Results: The mean age of the patients were 6.1 ± 4.1 years ranging between 4 month and 15 years. Male to female ratio was 1.8. Thirty-three (71.1%) cases of scorpion stings came from rural areas. Twenty-six (57.8%) of the patients were stung by Androctonus crassicauda. The most common sting localization was the foot-leg (55.6%). The mean duration from the scorpion sting to hospital admission was 4.5 ± 2.6 hours. The most common findings at presentation were cold extremities (95.5%), excessive sweating (91.1%) and tachycardia (77.7%). The mean leukocyte count, and serum levels of glucose, lactate dehydrogenase, creatine phosphokinase and international normalized ratio were found above the normal ranges. Prazosin was used in all patients, dopamine in 11 (24.4%) and Na-nitroprusside in 4 (8.8%) patients. Two children died (4.4%) due to pulmonary oedema. These children, in poor clinical status at hospital admission, needed mechanical ventilation, and death occurred despite use of antivenin and prazosin in both of them. Conclusion: The current management of children with severe scorpion envenomation consists of administration of specific antivenom and close surveillance in a PICU, where vital signs and continuous monitoring enable early initiation of therapy for life-threatening complications. The aggressive medical management directed at the organ system specifically can be effective. Our data indicated that when admission to hospital is late, the beneficial effect of antivenom and/or prazosin is questionable in severe scorpion stings.

Severe acetaminophen poisoning treated with a fractionated plasma separation and absorption system: A case report

Sebe, A., Satar, S., Rana Alpay, N., Murt, M., Guvenc, B. — Mon, 16 Nov 2009 09:01:18 PST

Acetaminophen is an analgesic drug that is frequently used in suicide attempts. In this paper, we report on a 17-year-old girl who was admitted to an emergency department 15 hours after taking acetaminophen pills in a suicide attempt. Her serum acetaminophen level was 73 mg/L on admission; she had elevated liver enzymes suggesting hepatic necrosis. She was started on N-acetyl cystein (NAC), and treated successfully with a fractionated plasma separation and absorption system.