Metallothionein and occupational exposure to cadmium.

The relationship between metallothionein (MT), chronic exposure to cadmium (Cd), and renal function was investigated in 53 men who were occupationally exposed to Cd. The aim was to determine if MT is a potential biological monitor for chronic exposure to Cd which would be useful for preventing Cd nephropathy. In this study MT excretion, serum MT, and serum creatinine concentrations were significantly higher in subjects with abnormal renal function who had been exposed to Cd. MT excretion was also linearly related on an individual basis to protein excretion, beta 2-microglobulin (beta 2-M) excretion, and cumulative time weighted exposure (dose). MT excretion was also a better predictor of dose than either beta 2-M excretion or Cd excretion. The findings suggest that MT is a potential biological monitor for chronic Cd exposure that would be useful for preventing Cd-induced nephropathy. Further studies of non-specific nephropathies and MT are needed to determine if MT is a specific indicator of proximal tubule function secondary to chronic exposure to Cd.     

Problems in teaching gerontological facts to medical students (author's transl)]

During the medical training the geriatric problems are still not observed enough, and they are not taken into consideration yet in the medical indexes for the different sections of the medical examination either. Geriatrics though, which have to be more extensive because of the multiplicity of the disease, can counteract to the necessary specialicing in the medical schools.     

Vergleichende Untersuchungen über die Entwicklung der apikalen Basis nach kieferorthopädischer Behandlung mit der aktiven Platte und dem Funktionsregler

Ohne ZusammenfassungMit 2 Abbildungen     

Catalytic activity and isoform-specific inhibition of rat cytochrome p450 4F enzymes

Arachidonic acid is omega-hydroxylated to 20-hydroxyeicosatetraenoic acid (20-HETE), which has effects on vasoactivity and renal tubular transport and has been implicated in the regulation of blood pressure. Cytochrome p450 (p450) 4A isoforms are generally considered the major arachidonic acid omega-hydroxylases; however, little is known about the role of rat CYP4F isoforms in 20-HETE formation. The rat CYP4F isoforms, CYP4F1, CYP4F4, CYP4F5, and CYP4F6, were heterologously expressed in Escherichia coli, and their substrate specificity in fatty acid metabolism was characterized. Substrate-binding assays indicated that leukotriene B(4) (LTB(4)) and arachidonic acid bound CYP4F1 and CYP4F4 in a type-I manner with a K(s) of 25 to 59 microM, and lauric acid bound CYP4F4 poorly. Reconstituted CYP4F1 and CYP4F4 catalyzed the omega-hydroxylation of LTB(4) with a K(m) of 24 and 31 microM, respectively, and CYP4F5 had minor activity in LTB(4) metabolism. Importantly, CYP4F1 and CYP4F4 catalyzed the omega-hydroxylation of arachidonic acid with an apparent k(cat) of 9 and 11 min(-1), respectively. Lauric acid was a poor substrate for all of the CYP4F isoforms, and CYP4F6 had no detectable fatty acid omega-hydroxylase activity. The p450 omega-hydroxylase inhibitors 17-octadecynoic acid, 10-undecynyl sulfate, and N-methylsulfonyl-12,12-dibromododec-11-enamide showed isoform-specific inhibition of CYP4F1- and CYP4F4-catalyzed omega-hydroxylation of arachidonic acid and potency differences between the CYP4A and CYP4F isoforms. These data support a significant role for CYP4F1 and CYP4F4 in the formation of 20-HETE and identify p450 inhibitors that can be used to understand the relative contribution of the CYP4A and CYP4F isoforms to renal 20-HETE formation.     

Effects of a 20-HETE antagonist and agonists on cerebral vascular tone

This study examined the effects of a 20-hydroxyeicosatetraenoic acid (20-HETE) antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (WIT002) and two agonists, 4-amino-N-(20-hydroxy-eicosa-5(Z),14(Z)-dienoyl) benzenesulfonamide (ABSA) and 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (WIT003), on the diameter of rat middle cerebral arteries in vitro and on cerebral blood flow in vivo. WIT003, ABSA and 20-HETE all had a similar effect to reduce the diameter of the middle cerebral artery by 26%. WIT003 and 20-HETE both increased intracellular Ca2+ concentration ([Ca2+]i) in vascular smooth muscle cells isolated from the middle cerebral artery. In contrast, WIT002 had no effect on the basal diameter of the middle cerebral artery but it attenuated the vasoconstrictor responses and the rise in [Ca2+]i in vascular smooth muscle cells following administration of 20-HETE and 5-hydroxytryptamine (5-HT). WIT003 partially restored the vasoconstrictor response to 5-HT in the middle cerebral artery after administration of an inhibitor of the endogenous synthesis of 20-HETE. Infusion of the 20-HETE agonists, WIT003 and ABSA, into cisterna magna of rats reduced baseline cerebral blood flow by 20%, whereas administration of the 20-HETE antagonist, WIT002, had no effect. Intracisternal injection of WIT002 attenuated the fall in cerebral blood flow following injection of blood into the cisterna magna, whereas administration of the 20-HETE agonist, ABSA, potentiated this response. These findings indicate that the 20-HETE agonists, WIT003 and ABSA, increase cerebral vascular tone both in vivo and in vitro and suggest blocking the vasoconstrictor actions of 20-HETE may be useful to prevent the acute fall in cerebral blood flow following subarachnoid hemorrhage.     

The prevalence of psychiatric disorder among a community sample of crack cocaine users: an exploratory study with practical implications

The Diagnostic Interview Schedule for DSM-IV was used to assess the lifetime prevalence of psychiatric disorder among not-in-treatment crack cocaine users (N = 313). The most common dependencies involved cocaine (59.7%), alcohol (37.7%), and cannabis (12.1%). The most common nondependency disorders were antisocial personality disorder (ASPD; 24%), depression (17.8%), and posttraumatic stress disorder (PTSD; 11.8%). Comorbidity was present in 36.4% of the sample. Proportionately more white than black users were dependent on cocaine, alcohol, amphetamine, and sedative-hypnotics. More white than black users experienced ASPD, depression, PTSD, and attention deficit disorder. Proportionately fewer black users suffered comorbid disorders. Proportionately more men had ASPD, whereas more women had PTSD and phobias. Multinominal modeling revealed that black users and users with a high school education were less likely to have comorbid disorders; married users were less likely to have nondependency disorders. White crack users were more likely to have comorbidity, complicating their treatment.     

MDMA/Ecstasy use among young people in Ohio: perceived risk and barriers to intervention

In the past several years, the use of MDMA (Ecstasy) has increased substantially in the United States and in many countries around the world. Although this increase has been associated with the dance club and rave scenes, Ecstasy use has expanded into new settings. At the same time, the diversity of people using the drug has also grown. Given the increasing, although unclear, evidence that MDMA has the potential to cause neurotoxicity and various psychological problems under certain conditions among humans, understanding how active users perceive the risks associated with Ecstasy use can help to inform prevention and intervention approaches. Based on audiotaped focus groups and individual interviews conducted with 30 Ecstasy users in Dayton and Columbus, Ohio, this article explores these and other issues. Results demonstrate that beyond the risk of obtaining something potentially deadly instead of MDMA, most users do not associate risks of neurotoxicity or psychological problems with Ecstasy use. Active users look to harm-reduction approaches for answers to using Ecstasy safely; prevention messages like, "just say no to drugs" are largely ignored. Because Ecstasy is commonly used among small groups of friends, peer leader or other social network intervention approaches may be promising.     

Sources of information about MDMA (3,4-methylenedioxymethamphetamine): perceived accuracy, importance, and implications for prevention among young adult users

The goal of this cross-sectional study was to assess the perceived accuracy and the importance of various sources of information about MDMA/ecstasy among young adult users. A respondent driven sampling plan was used to recruit a community sample of recent ecstasy users (n = 304), aged 18-30, in Ohio, who responded to structured interviews. Friends, drug abuse treatment programs, and physicians were perceived to be the most accurate sources of information about ecstasy by 45.7, 37.2, and 30.3% of the sample, respectively. Friends were considered the most important source of information about ecstasy (40.2%), followed by web sites like DanceSafe (16.2%), and MTV/VH1 television specials (6.9%). About half the sample used the Internet to obtain information about ecstasy, with younger and more educated participants significantly more likely to do so. Educated users were also significantly more likely to consider the Internet to be an important source of information. Web sites like DanceSafe were visited by four times as many users as government-sponsored web sites. Findings support the development of peer-oriented, network strategies to reach ecstasy users with prevention messages. Efforts to make prevention web sites more attractive should be considered.