Recent update on the PPAR alpha-null mouse

The most important commercially available nitro- and aminobenzenes and the explosive trinitrobenzene were tested for mutagenicity in the Salmonella typhymurium TA 98 and TA 100 both in the absence and presence of S 9. Ten of the 14 compounds tested (71%) were mutagenic. All the substances showed positive results in TA 98 and 4 substances were also mutagenic in TA 100. The three diaminobenzenes and 4-nitroaniline were mutagenic only with metabolic activation. All other compounds did not require the addition of S 9. Only nitrobenzene, 1,2-dinitrobenzene, aniline and 2-nitroaniline were negative in both strains. In summary, all substances that are derived from nitrobenzene or aniline by addition of a nitro group in the meta- or para-position were mutagenic, whereas nitrobenzene and aniline themselves and their ortho-derivates were nonmutagenic. The possible relationships between the position of the substituents and the mutagenicity are discussed.     

Cutaneous hyalohyphomycosis caused by Fusarium solani in a loggerhead sea turtle (Caretta caretta L.)

Fusarium solani was reported as the agent of a cutaneous infection in an injured sea turtle collected in the Mediterranean Sea. The turtle was treated with both a topical 10% solution of iodine in alcohol and ketoconazole. The source of the causal agent was traced to the sand in the tank in which the turtle was maintained. The strain was only sensitive in vitro to amphotericin B and was resistant to 5-fluorocytosine, fluconazole, itraconazole, and ketoconazole.     

Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features

The number of nosocomial infections caused by Acinetobacter baumannii has increased in recent years. During a 12-month study, there were 1.8 episodes of A. Baumannii bacteremia per 1,000 adults admitted to a hospital in Seville, Spain. Seventy-nine patients were included in the study. A. baumannii bacteremia occurred after a mean (+/- SD) hospitalization of 18 +/- 20 days. In all cases the infections were acquired nosocomially; 71% wee acquired in intensive care units. Ampicillin/ sulbactam was found to be the most active agent against A. baumannii. The common source of the bacteremia was the respiratory tract (32 cases [71%]). Twenty patients (25%) had septic shock, and 24 (30%) had disseminated intravascular coagulation (DIC). Treatment with imipenem or ampicillin/sulbactam was most effective (cure rates, 87.5% and 83%, respectively). The deaths of 27 patients (34%) were related to A baumannii bacteremia. The presence of DIC (odds ratio [OR] = 116.4; P < .0001) and inappropriate antimicrobial treatment (OR = 15.2; P < .01) were independently associated with mortality. We conclude that most A. baumannii isolates are multiresistant and that nosocomial A. baumannii bacteremia may cause severe clinical disease that is associated with a high mortality.     

Comparative cytotoxicity of 14 novel selenocysteine se-conjugates in rat renal proximal tubular cells

Recently, Se-substituted selenocysteine conjugates were proposed as potential prodrugs to target biologically active selenol compounds to tissues containing high activities of cysteine conjugate beta-lyases, such as the kidneys. However, several selenium compounds are known to be relatively toxic compounds. In the present study, the cytotoxicity of 14 selenocysteine Se-conjugates was determined in freshly isolated rat renal proximal tubular cells (RPTC). The results of this study show that four selenocysteine Se-conjugates with alkyl substituents (methyl, ethyl, n-propyl, and n-butyl) did not cause significant cytotoxicity to RPTC up to concentrations of 500 microM after 90 min of incubation. Also, no effect was observed on mitochondrial functioning as indicated by the unaffected mitochondrial membrane potential (delta psi). Se-(i-Propyl)-selenocysteine, however, appeared to be a cytotoxic compound, causing time- and dose-dependent cytotoxicity, and caused a decrease of delta psi in remaining viable cells. Aminooxyacetic acid (AOAA) provided significant protection against cell death of Se-(i-propyl)-selenocysteine, pointing to involvement of cysteine conjugate beta-lyase. AOAA, however, did not prevent the decrease of delta psi. Differentially substituted Se-(phenyl)-L-selenocysteine and Se-(benzyl)-L-selenocysteine conjugates appeared to be cytotoxic to RPTC at a concentration of 200 microM, as indicated by increased cell death and a decreased delta psi in remaining viable cells. Within the Se-benzyl-series, Se-(4-methoxybenzyl)-L-selenocysteine was the most toxic conjugate, whereas Se-(4-chlorophenyl)-L-selenocysteine was the most toxic conjugate of the Se-phenyl compounds. The selenocysteine Se-conjugates with nonsubstituted phenyl and benzyl substituents were nontoxic at 200 microM, but caused significant cell death at a concentration of 500 microM. Preincubation with AOAA, an inhibitor of cysteine conjugate beta-lyase, provided only partial protection against the cytotoxicity of Se-(phenyl)-L-selenocysteine (500 microM) and Se-(4-methoxybenzyl)-L-selenocysteine (200 microM). AOAA did not protect against cytotoxicity of the other conjugates, suggesting direct effects of these compounds or involvement of alternative routes of bioactivation. This study demonstrates that cytotoxicity of selenocysteine Se-conjugates is strongly dependent on the nature of the Se-bound substituent. The nontoxic Se-(alkyl)-Se-conjugates may be promising candidates for further evaluation for chemopreventive activities.     

Hydrocortisone and 11-desoxycortisone modify acetylcholine receptor channel gating

Over the years several methods for evaluating mediastinal involvement in Hodgkin's disease have been applied to chest radiographs and conflicting results have been reported. In a retrospective study of 104 patients we evaluated interobserver variability in assessing mediastinal involvement and investigated various cut-off points for mediastinal size as to their ability to identify patients with high- and low-risk for recurrence. For mediastinal involvement the concordance rate for two reviewing radiologists was 94% (98/104) and compared with prior assessment by outside radiologists the concordance rates were 90% (94/104) and 88% (92/104), respectively. A good correlation between the reviewing radiologists was found for the quantitative evaluation of mediastinal diameter and thoracic ratios. ROC curves and relative risk figures were used to investigate the various cut-off points for mediastinal width and for the ratios of the maximal mediastinal diameter to the chest diameter at Th 5-6 (M1) and to the chest diameter at the widest thoracic level (M2). Neither the ROC curve analysis nor the use of relative risk figures revealed a cut-off point clearly more accurate in predicting recurrence. In conclusion, our results do not suggest that interobserver variability in mediastinal assessment, differences in the method of mediastinal measurement, or the cut-off points applied to mediastinal width can explain the discrepancies in the reported data on the prognostic value of mediastinal width in Hodgkin's disease, but rather factors such as patient selection and differences in treatment given may be responsible.     

Regulation of prostaglandin endoperoxide H2 synthase in term human gestational tissues

The distribution in the chicken intestine of neuropeptide-immunoreactive (IR) ganglion cells and nerve fibres was investigated immunohistochemically. There were four kinds of ganglion cells: vasoactive intestinal polypeptide (VIP)-, substance P (SP)-, galanin (GAL)- and somatostatin (SOM)-IR cells in the submucous plexus (SMP) of the whole intestine and in the myenteric plexus (MYP) in the small intestine excluding VIP-IR ones. These peptide-containing fibres were found consistently but their distribution was variable in the mean areas in different regions of the intestinal wall. They seemed to be intrinsic. Comparing the jejunum and rectum in density and variation, the characteristics of innervation were as follows: villi in both intestines received more VIP-IR fibres than the other three which showed no significant difference. Crypts were surrounded with SP-IR fibres; these were denser than the other three in the jejunum compared with the rectum. The mean areas of SOM- and GAL-IR fibres were four and six times larger than those in the rectum, respectively. The SMP was supplied with the six kinds of neuropeptide-IR fibres, and VIP-IR fibres were dominant in both sides. Areas of VIP-, SP- and SOM-IR fibres were about two times greater than in the jejunum. The area of VIP-IR fibres in the circular muscle was significantly larger than that of the other four in both intestines; their density in the rectum was bout two times higher than in the jejunum. The mean area of SP-IR fibres in jejunal circular muscle was 14 times larger than that in the rectum. The MYP was supplied with seven kinds of neuropeptide-IR fibres except that methionine enkephalin-IR was absent from the rectum. Of these seven fibres, SP- and VIP-IR fibres in the jejunum had the largest areas. However, GAL-IR fibres in the jejunum were about four times denser than in the rectum. We conclude that the jejunum is characterized by the dense distribution of neuropeptide-IR fibres in crypts and MYP whereas in the rectum they occur in SMP and circular muscle. Fig. 15 summarizes the connections described in the present study.     

Is the association between drug use and delinquency weakening?

In this paper we examine period or secular changes in the association between drug use and delinquency among Ontario adolescent students between 1983 and 1991. The results show that during this period drug use and drug-selling declined significantly, whereas reported non-drug-related delinquency increased. In addition to differing secular trends in rates of drug use and delinquent behaviour, the association between the two behaviours weakened. There was a steady decline in the correlations between drug use and delinquency across time, and the typological patterning of drug use and delinquency changed significantly.     

Transesophageal echocardiography diagnosis of perforation of the mitral valve secondary to infective endocarditis

We report on a patient with infective endocarditis and severe mitral regurgitation secondary to perforation in the base of the posterior mitral leaflet. Transthoracic echocardiography was inconclusive. Only transesophageal echocardiography could confirm the presence of vegetations, their characteristics and the existence of valvular perforation. We also review the literature on the contribution of transesophageal echocardiography to the diagnosis of infective endocarditis and its complications.