Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.
Abducens Nerve Diseases/*chemically induced/drug therapy ; Adult ; Aminobutyrates/*poisoning ; Enzyme Inhibitors/poisoning ; Herbicides/*poisoning ; Humans ; Male ; Seizures/chemically induced ; Surface-Active Agents/poisoning ; Unconsciousness/chemically induced

OBJECTIVEThe objective of this study was to investigate arsenic induced changes in blood delta-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination.

METHODSRat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (III) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration.

RESULTSIn vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (III and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (III) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (III), but at two higher concentrations (0.5 and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value.

CONCLUSIONSThe results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood ALAD inhibition and blood arsenic concentration than the individual treatment.

Administration, Oral ; Animals ; Arsenic Poisoning ; blood ; Arsenicals ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Injections, Intraperitoneal ; Male ; Mice ; Porphobilinogen Synthase ; antagonists & inhibitors ; blood ; Rats ; Succimer ; analogs & derivatives ; pharmacology

Animals ; Antioxidants ; pharmacology ; Carbon Tetrachloride Poisoning ; drug therapy ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; Enzyme Inhibitors ; pharmacology ; Male ; Mice ; Protective Agents ; pharmacology ; Ribonucleases ; antagonists & inhibitors

OBJECTIVETo observe the prophylactic effect of curcumin on hepatic fibrosis and the number, location, apoptosis of activated hepatic stellate cells (HSCs) in the livers and to discuss the relationship between the prophylactic effects and activated HSC.

METHODSA rat model of hepatic fibrosis was established by intraperitoneal injection of carbon tetrachloride. Curcumin doses of 5 mg, 10 mg, 20 mg per 100 gram per 100g of body weight were given to three groups of the model rats. No curcumin was given to one group of the model rats and it served as the control. After eight weeks, all rats were sacrificed and their left liver lobes were examined histopathologically with H.E and Masson stainings. Grades of hepatic fibrosis were evaluated according to the SSS system. Activated HSC was detected by the alpha-SMA immunohistochemistry staining. HSC apoptosis was detected by double-stainings of terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and desmin immunohistochemistry staining.

RESULTSDegrees (SSS system scores) of hepatic fibrosis in the curcumin groups were all less severe in comparison with those of the control group. Activated HSCs in the livers of the rats of the control group increased significantly compared with that of the treatment groups, and also fewer apoptotic HSCs were detected in the control group. On the contrary, fewer activated HSCs and more apoptotic HSCs were detected in the curcumin groups compared with those of the control group. The degrees of the effects were curcumin dose-dependent.

CONCLUSIONSCurcumin can prevent hepatic fibrosis. It can inhibit activation and proliferation of HSCs and induce HSCs apoptosis, which may be the mechanism(s) contributing to the prophylactic effects of curcumin on hepatic fibrosis.

Animals ; Apoptosis ; drug effects ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Curcumin ; therapeutic use ; Enzyme Inhibitors ; therapeutic use ; Hepatocytes ; pathology ; Liver Cirrhosis, Experimental ; pathology ; prevention & control ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of baicalin (Bai) on lung injury, the level of TNF-alpha in cultured liquid of pulmonary interstitial macrophage and the expression of heme oxygenase-1 (HO-1) in lung injury associated with paraquat poisoning.

METHODSRats were randomizedly divided into four groups: control group, PQ group, Bai group (Bai, 300 mg.kg(-1).d(-1)) and simple Bai group (Bai, 300 mg. kg(-1).d(-1)) (n = 10 in each group). The 2% PQ was injected (25 mg/kg) in PQ group. Bai was injected in the rats (300 mg.kg(-1).d(-1) x 3 d) through caudal vein after paraquat poisoning in Bai group. In simple Bai group, Bai was injected in the healthy rats (300 mg.kg(-1).d(-1) x 3 d). The samples were obtained three days after intraperitoneal administration of 2% paraquat (25 mg/kg). The injury of lung was estimated with HE dyeing and electron microscope. Pulmonary interstitial macrophage (PIM) were obtained, and then cultured for 24 hours. The content of TNF-alpha was evaluated. The expression of HO-1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). The expression of HO-1 protein was evaluated by Western blot analysis.

RESULTSThe lung tissue was normal in control group and simple Bai group. The degree of lung injury in PQ group was higher than that in control group by HE dyeing and electron microscope observation. The level of TNF-alpha expression in cultured PIM in Bai group [(484.2 +/- 39.5) microg/L] was lower than that in PQ group [(790.2 +/- 35.0) microg/L], but higher than that in the control group [(121.6 +/- 19.2) microg/L] (P < 0.05). The expression of HO-1 mRNA and protein [(59.8 +/- 5.40) and (122.0 +/- 31.98)] in Bai group were higher than those in PQ group [(45.9 +/- 5.82) and (77.92 +/- 10.23)] (P < 0.05).

CONCLUSIONThe lung injury associated with paraquat poisoning was alleviated by baicalin, which was possibly related to the decrease of level of TNF-alpha in cultured PIM and the increase of the expression of HO-1 mRNA and protein.

Animals ; Enzyme Inhibitors ; pharmacology ; Flavonoids ; pharmacology ; Heme Oxygenase-1 ; biosynthesis ; genetics ; Lung ; metabolism ; pathology ; Macrophages, Alveolar ; metabolism ; Male ; Paraquat ; poisoning ; RNA, Messenger ; biosynthesis ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult ; metabolism ; pathology ; Tumor Necrosis Factor-alpha ; biosynthesis

OBJECTIVETo investigate the therapeutic effects of perindopril, an angiotensin-converting enzyme inhibitor, and valsartan, an angiotensin II receptor blocker on TGFbeta1 and TGFbeta receptor II mRNA, Smad3 and Smad7 on rat liver fibrosis.

METHODS60 Wistar rats were randomly divided into four groups (each group, n=15). Group 1 rats were not treated and served as healthy controls. The rats of groups 2,3,and 4 were injected with CCl(4) which induced liver fibrosis. After four weeks, group 3 rats started a treatment of perindopril, and group 4 rats with valsartan. All rats were sacrificed at the eighth week and their blood and livers were collected for analysis. The effects of perindopril and valsartan were evaluated by the levels of transforming growth factor-beta1 (TGFb1), and TGF receptor (TGFb1RII) mRNA in liver tissues by RT-PCR, the expressions and sites of TGFb1, Smad3 and Smad7 in liver tissue by immunohistochemical staining. The liver histopathology was also examined with HE staining, and the hydroxyproline in the liver and serum hyaluronic acid (HA) were examined using biochemsitry and RIA.

RESULTSCompared with the control group, the levels of TGFb1, TGFb1RII mRNA and the expression Smad3 were significantly decreased in the two treated groups, and the expression of Smad7 was also remarkably increased in the livers of rats treated with perindopril or valsartan. The histological changes of fibrosis, the hydroxyproline in the livers and HA were also improved in the treated rats.

CONCLUSIONPerindopril and valsartan have a protective effect on liver injury and can inhibit hepatic fibrosis induced by CCl(4) in rats. Their mechanisms may be associated with their effects of down-regulating TGFb1, TGFb1RII mRNA and smad3, and up-regulating Smad7 which then resulted in suppressing the activation of hepatic stellate cells.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; Male ; Perindopril ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Transforming Growth Factor beta ; biosynthesis ; genetics ; Smad3 Protein ; biosynthesis ; genetics ; Smad7 Protein ; biosynthesis ; genetics ; Tetrazoles ; pharmacology ; Transforming Growth Factor beta ; biosynthesis ; genetics ; Transforming Growth Factor beta1 ; Valine ; analogs & derivatives ; pharmacology ; Valsartan