Update: hydrogen cyanamide-related illnesses--Italy, 2002-2004.
(17/62)Hydrogen cyanamide is used in agriculture as a plant growth regulator and is applied to many deciduous plants to stimulate uniform budbreak after dormancy, resulting in uniform flowering and maturity. Hydrogen cyanamide is highly toxic, and adverse health effects from contact include severe irritation and ulceration of the eyes, skin, and respiratory tract. The substance also inhibits aldehyde dehydrogenase and can produce acetaldehyde syndrome (e.g., vomiting, parasympathetic hyperactivity, dyspnea, hypotension, and confusion) when exposure coincides with alcohol use. After Dormex (Degussa AG, Trostberg, Germany), a pesticide product containing hydrogen cyanamide (49% by weight), was introduced in Italy in 2000, a total of 23 cases of acute illness associated with exposure to this chemical were identified in early 2001. This led to a temporary suspension of sales and usage of Dormex on February 23, 2002, and strengthening of protective measures, as specified on the pesticide label when sales were resumed on June 20, 2003. This report describes 28 additional cases of hydrogen cyanamide-related illness that occurred during 2002-2004, 14 of which occurred after sales resumed. These illnesses suggest that the preventive measures adopted in Italy in 2003 to protect workers using hydrogen cyanamide are inadequate. Workers exposed to hydrogen cyanamide should be provided adequate information, training, personal protective equipment (PPE), and engineering controls. (+info)
Protein adduct species in muscle and liver of rats following acute ethanol administration.
(18/62)AIMS: Previous immunohistochemical studies have shown that the post-translational formation of aldehyde-protein adducts may be an important process in the aetiology of alcohol-induced muscle disease. However, other studies have shown that in a variety of tissues, alcohol induces the formation of various other adduct species, including hybrid acetaldehyde-malondialdehyde-protein adducts and adducts with free radicals themselves, e.g. hydroxyethyl radical (HER)-protein adducts. Furthermore, acetaldehyde-protein adducts may be formed in reducing or non-reducing environments resulting in distinct molecular entities, each with unique features of stability and immunogenicity. Some in vitro studies have also suggested that unreduced adducts may be converted to reduced adducts in situ. Our objective was to test the hypothesis that in muscle a variety of different adduct species are formed after acute alcohol exposure and that unreduced adducts predominate. METHODS: Rabbit polyclonal antibodies were raised against unreduced and reduced aldehydes and the HER-protein adducts. These were used to assay different adduct species in soleus (type I fibre-predominant) and plantaris (type II fibre-predominant) muscles and liver in four groups of rats administered acutely with either [A] saline (control); [B] cyanamide (an aldehyde dehydrogenase inhibitor); [C] ethanol; [D] cyanamide+ethanol. RESULTS: Amounts of unreduced acetaldehyde and malondialdehyde adducts were increased in both muscles of alcohol-dosed rats. However there was no increase in the amounts of reduced acetaldehyde adducts, as detected by both the rabbit polyclonal antibody and the RT1.1 mouse monoclonal antibody. Furthermore, there was no detectable increase in malondialdehyde-acetaldehyde and HER-protein adducts. Similar results were obtained in the liver. CONCLUSIONS: Adducts formed in skeletal muscle and liver of rats exposed acutely to ethanol are mainly unreduced acetaldehyde and malondialdehyde species. (+info)
Rosiglitazone relieves acute ethanol-induced hangover in Sprague-Dawley rats.
(19/62)AIMS: To assess the efficacy of rosiglitazone in blocking ethanol-induced hangover in rats. METHODS: Rats injected with ethanol (4 g/kg body weight) were subjected to social interaction tests. Levels of aldehyde dehydrogenase 2 (ALD2), involved in an anti-hangover mechanism, were measured by semi-quantitative RT-PCR and western blot analysis. RESULTS: Rosiglitazone caused an upregulation of mitochondrial ALD2, thus significantly detoxifying acetaldehyde. CONCLUSIONS: Rosiglitazone alleviated the symptoms of ethanol-induced hangover by inducing ALD2 expression; this result was reconfirmed by eliminating the effect of rosiglitazone by injecting cyanamide, an ALD2 inhibitor. (+info)
Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: is there still a role for these drugs?
(20/62)Disulfiram and calcium carbimide are two alcohol deterrants widely used in alcoholism treatment, however, there exist great concerns over their safety. Reports on hepatotoxicity, mainly related to disulfiram therapy, have been published. The hepatotoxic potential of calcium carbimide is less well characterized. Here, we describe four cases of liver damage related to this therapeutic group that were submitted to a Registry of hepatotoxicity and point out the limitations that we face when prescribing these compounds. A reassessment of the role of these compounds in the management of alcohol dependence is clearly needed. (+info)
Quantification of cyanamide contents in herbaceous plants.
(21/62)Cyanamide (NH2CN) is found in nature, although it has long been recognized as an industrial product. Distribution of cyanamide in the plant kingdom was investigated using a direct quantitative determination method to detect and measure cyanamide by stable isotope dilution gas chromatography-mass spectrometry (the SID-GC-MS method). The SID-GC-MS method proved to be a robust way to quantify cyanamide contents in the extracts of 101 species of herbaceous plants. The average recovery of cyanamide from all plants tested was 55.6+/-20.3%. Vicia villosa and V. cracca contained cyanamide at 369-498 microg/gFW and 3,460-3,579 microg/gFW respectively, while the other 99 species contained no detectable cyanamide (<1 microg/gFW). This result suggests that distribution of cyanamide in the plant kingdom is limited and uneven. (+info)
Enhancement of the ambulation-increasing effect of opioid analgesics by ethanol in mice.
(22/62)The interaction between opioid analgesics (morphine and buprenorphine) and central depressants (ethanol, pentobarbital and diazepam) was investigated by means of ambulatory activity in mice. The ambulation-increasing effect of both morphine (10 mg/kg, s.c.) and buprenorphine (1 mg/kg, s.c.) was enhanced by the combined administration of ethanol (0.8-3.2 g/kg, p.o.) in a dose-dependent manner. Naloxone (0.1 mg/kg, s.c.) was effective for reducing the enhanced ambulatory activity. The pretreatment with Ca-cyanamide (5 mg/kg, p.o., 30 min before) reduced the enhancement of the ambulation-increasing effect induced by the combined administration of opioid analgesics with ethanol, although it scarcely modified that of morphine and buprenorphine alone. On the other hand, neither pentobarbital (1-30 mg/kg, s.c.) nor diazepam (0.25-2 mg/kg, s.c.) modified markedly the ambulation-increasing effect of morphine and buprenorphine. The present results suggest that ethanol specifically interacted with opioid analgesics when the mouse's ambulatory activity was used as the indicator. (+info)
Cutaneous reactions simulating erythema multiforme and Stevens Johnson syndrome due to occupational exposure to a plant-growth regulator.
(23/62)BACKGROUND: In India, hydrogen cyanamide (Dormex) is a plant growth regulator used mainly for the bud-breaking of grapevines. The use of this chemical may result in severe cutaneous reactions simulating erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: Studies were conducted on four seasonal grapevine workers who developed severe cutaneous reactions following the unprotected use of Dormex (hydrogen cyanamide). RESULTS: Two of the patients had EM-like skin lesions and the other two developed SJS-TEN-like skin lesions. A latent period of 5-7 days existed between the contact with the chemical and the development of the skin lesions. The histopathological picture was suggestive of EM. All the patients responded to systemic steroids and antihistamines. CONCLUSIONS: Hydrogen cyanamide may act as a hapten, initiating cytotoxic immunological attack on keratinocytes, resulting in EM- and SJS-TEN-like clinical picture. Awareness regarding such severe cutaneous reactions due to the inappropriate handling of Dormex is required. The use of personal protection equipment while handling agricultural chemicals is essential. (+info)
PPARalpha and PPARbeta are differentially affected by ethanol and the ethanol metabolite acetaldehyde in the MCF-7 breast cancer cell line.
(24/62)The activity and/or the level of the peroxisome proliferator-activated receptors (PPARs) in liver and oligodendrocytes are regulated by ethanol. Despite the association between ethanol consumption and breast cancer risk, and the increasing evidence for an involvement of PPARs in some cancers, there have been no studies on the effect of ethanol or its metabolite acetaldehyde on PPARs in breast cancer. Using the MCF-7 breast cancer cell line, we examined the relationship between ethanol and its metabolite acetaldehyde on PPARalpha and PPARbeta transactivation. Ethanol (20 mM) reduced the potency of the PPARbeta ligand GW0742, evident by a rightward shift in the GW0742 dose-response curve, whereas for PPARalpha activation by GW7647, ethanol mediated its effects primarily through reducing efficacy as evidenced by a reduction in maximal response. Using the enzyme inhibitors 4-methylpyrazole and cyanamide and the metabolite acetaldehyde, we showed that PPARalpha and PPARbeta are differentially modulated by ethanol and acetaldehyde. While acetaldehyde is responsible for the inhibition of PPARalpha ligand inhibition with a concentration that inhibits 50% of activity (IC50) of 111 nM, acetaldehyde has no effect on PPARbeta or its ligand activation. Instead, inhibition of PPARbeta transactivation is mediated directly by ethanol. The differential effect of ethanol and acetaldehyde on PPARalpha and PPARbeta further underscores the differences between these receptors and may indicate the relevance of PPARs in the effects of ethanol in the human breast. (+info)