Effects of graft pooling of foetal rat and mouse tissue and immunosuppression in the 6-hydroxydopamine rat model of Parkinson’s disease

 We employed intracerebral co-transplantation of foetal xenogeneic striatal mouse tissue and allogeneic rat substantia nigra into the adult rat brain to elucidate the effects of xenogeneic mouse graft on the function and survival of an allogeneic rat graft in 6-hydroxydopamine lesioned Sprague-Dawley rats. Foetal mouse striatum (STR) and rat substantia nigra (VM) were transplanted as non-pooled separate deposits or a pooled cell suspension with or without cyclosporin A (Cy A). Immunosuppressed recipients of pooled rat and mouse co-grafts showed a significantly better compensation of amphetamine-induced rotational behaviour compared with non-immunosuppressed animals with pooled rat and mouse co-grafts 3 and 6 weeks post-grafting.Tyrosine hydroxylase (TH) immunohistochemistry revealed a non-significant reduction in survival in pooled (1806.3±367.5 cells) rat and mouse co-transplants without immunosuppression compared with immunosuppressed pooled (3383.3±732.7 cells) animals with allo- and xenogeneic tissue and controls (3506.4±839.3 cells). Graft volumes were significantly reduced in pooled transplants without immunosuppression (0.1±0.026 mm³; ANOVA post-hoc SchefféF-test, P<0.0001) compared with immunosuppressed recipients (0.7±0.1 mm³) and controls (0.6±0.1 mm³). In non-pooled allo- and xenogeneic grafts without immunosuppression the survival rate of the TH-immunoreactive cells and graft volumes were reduced (2359.3±479.5 cells; 0.2±0.043 mm³) compared with immunosuppressed animals (2927.3±946.6 cells; 0.6±0.2 mm³) and controls (2701.1±693.8 cells; 0.3±0.1 mm³) without reaching a level of significance. Rejection of mouse tissue was observed in all non-immunosuppressed recipients. In summary: (i) continued immunosuppression yielded significant beneficial effects on function and beneficial effects on survival of pooled grafts with an immunogenetic disparity; (ii) the rejection of a xenogeneic graft component may compromise survival and function of other, allogeneic graft components; and (iii) transplantation of non-pooled allo- and xenogeneic tissues may result in a better survival of the graft compared with pooled cell suspensions. Received: 25 March 1996 / Accepted: 1 December 1996     

Mercury from gold minings in the Pantanal of Pocone (Mato Grosso,Brazil)

The Pocone gold minings are situated in the Bento Gomes River Basin, at the border of the Pantanal of Mato Grosso. Gold-bearing quartz veins are removed from the subsoils, milled with water, centrifuged and the heavier fraction is subsequently mixed with mercury for gold separation. The gold mining activities caused a very intensive landscape change, threatening many environmental processes like sediment control and storage and recycling capacity of mercury. Cold Vapor Atomic Fluorescence System (CVAFS) was used to determinate total mercury in water, suspended material and sediments from Bento Gomes River, sampled monthly for 1 year. Apart from the fact that mercury concentrations are low in water and bottom sediments, they are slightly higher in relation to background levels measured in the area. The concentration in suspended material is also lower than other rivers with gold mining activities, but the floodplains of the Bento Gomes River act as mercury sinks. Therefore, the discharge of mercury into the Pantanal floodplain should be avoided, in spite of actual contamination of the system being very low.     

Subjective work noise: A major risk factor in myocardial infarction

Summary The relationship between subjective work noise exposure and the risk of myocardial infarction (MI) was assessed in a population based casecontrol study. 395 MI patients (31–65 years) were compared to 2148 controls from a random population sample with the same age/sex distribution. The relative risk (RR) for MI—adjusted for control variables (smoking, age, social status, etc.)—was found to increase significantly and steadily with noise category. Subjective work noise exposure was the second greatest risk factor for MI after smoking. Possible bias due to overreporting of subjective noise exposure is discussed. Interdisciplinary studies on the relationship between cardiovascular diseases and workrelated stressors including subjective and objective noise assessment are needed to quantify the risk of MI due to work noise.

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Zusammenfassung In einer bevölkerungsbezogenen Fall-Kontroll-Studie wurde der Zusammenhang zwischen der subjektiven Arbeitslärmbelastung und dem Herzinfarktrisiko untersucht. 395 Herzinfarktpatienten im Alter von 31 bis 65 Jahren wurden mit 2148 Kontrollpersonen aus einer Zufallsstichprobe mit gleicher Alters- und Geschlechtsverteilung verglichen. Das relative Risiko für Herzinfarkt—adjustiert bezüglich mehrerer Einflussvariablen wie Rauchen, Alter, Sozialstatus usw.—stieg signifikant und monoton mit der Arbeitslärmbelastung an. Die subjektive Arbeitslärmbelastung erwies sich als der zweitwichtigste Risikofaktor für Herzinfarkt nach dem Rauchen. Mögliche Fehler wie z.B. Überbewertung der subjektiven Lärmbelastung werden diskutiert. Interdisziplinäre Studien zum Zusammenhang zwischen kardiovaskulären Erkrankungen und arbeitsplatzbezogenen Stressoren mit Erfassung der subjektiven und der objektiven Lärmbelastung sind notwendig, um das Herzinfarktrisiko durch Arbeitslärm zu quantifizieren.

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Résumé Le rapport entre la perception subjective de bruit gênant et le risque d'infarctus du myocarde (IM) fait l'objet d'une étude comparative portant sur 395 malades (IM) âgés de 31 à 65 ans et 2148 cas témoins sortis d'un sondage aléatoire parmi la population générale tout en assurant la même distribution d'âge et de sexe. II s'avère que—après la rectification exigée par les variables telles que consommation de tabac, âge, couche sociale, etc.—le risque relatif (RR) de IM augmente de manière significative et constante avec le gêne causé par le bruit au lieu de travail. Pour le IM, la perception subjective du bruit vécu au lieu de travail est le deuxième facteur de risque, son importance n'étant dépassée que par le tabagisme. Les auteurs discutent l'incidence possible d'une notification exagérée de bruit gênant. Afin de calculer le risque d' IM attributable au bruit perçu au lieu de travail, des études interdisciplinaires devraient être réalisées pour examiner les liens entre les maladies cardiovasculaires et les stresseurs liés au travail, y compris l'évaluation subjective et objective du bruit.

     

Frontal versus transcorneal stimulation to induce maximal electroshock seizures or kindling in mice and rats

Frontal stimulation, i.e. electrical stimulation where electrodes are pressed on the skin of the intact frontal skull of mice or rats, may represent a more humane alternative to the widely used transcorneal stimulation to induce electroshock seizures. The aim of this work was to directly compare transcorneal and frontal stimulation in eliciting maximal electroshock-induced seizures (MES) in mice and the anticonvulsant effect of carbamazepine (CBZ) and phenytoin (PHT) on thus produced seizures. In addition, we stimulated mice and rats repeatedly via transcorneal and frontal electrodes to see whether kindling is produced by this procedure. Two electroshock tests were used in mice, i.e. maximal electroshock seizure threshold (MEST) test and MES generated by supramaximal stimulation (50 mA). Frontal stimulation resulted in lower convulsive threshold than in the case of corneal stimulation. Both CBZ and PHT produced dose-dependent increases in seizure threshold for both sites of stimulation, i.e. transcorneal and frontal. As regards type of electrodes, higher doses of PHT were required to increase seizure threshold in the case of frontal than transcorneal stimulation. Supramaximal stimulation (50 mA) yielded comparable ED₅₀ values regardless of the site of stimulation. Furthermore, once-daily stimulation of mice, regardless of the placement of electrodes, did not induce any changes in convulsive threshold. We also attempted to kindle mice and rats via corneal and frontal electrodes by repetitive electrical stimulation using currents which initially did not produce generalized clonic seizures. Mice were stimulated once daily for 2 s with 3 mA (corneal electrodes) or 2 mA (frontal electrodes) and rats were stimulated twice daily for 4 s at 8 mA (corneal electrodes) or 5 mA (frontal electrodes). With corneal stimulation in rats there was a clear progression of kindling development which was not the same in nature when compared with corneally-stimulated mice. Frontal stimulation did not produce kindling. Moreover, corneal stimulation was better tolerated by rats, while in mice high mortality was seen after either method of current delivery. Our data indicate that frontal electrodes can be used as an alternative to transcorneal stimulation to produce MES by supramaximal or threshold current intensities as screening procedures in antiepileptic drug (AED) development. Nevertheless, this type of stimulation cannot be used to produce minimal electroshock seizures and seems not to be useful to produce kindling in rats and mice.     

Tumor-associated glycoprotein-72 serum levels complement carcinoembryonic antigen levels in monitoring patients with gastrointestinal carcinoma. A longitudinal study

Eighty-two patients diagnosed with gastrointestinal (GI) adenocarcinoma were evaluated before and for 26 months after primary tumor resection for the presence of two serum tumor markers: tumor-associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA). Elevated TAG-72 and CEA serum levels were found preoperatively in 32 (39%) and 34 (41.5%) of the 82 patients, respectively. The percentage of patients with elevated serum levels of either TAG-72 or CEA was 56.1% (46 of 82). Twelve (15%) patients who had normal CEA serum levels had elevated TAG-72 serum levels, and conversely, serum from 14 (17%) patients who were TAG-72 negative were CEA positive. Forty-five of the 82 patients were diagnosed with advanced disease (i.e., Stages C and D for colorectal, Stages III and IV for stomach), and 29 (64.4%) and 26 (57.8%) of those patients had elevated serum levels of TAG-72 or CEA, respectively. Elevated levels of either TAG-72 or CEA, however, were found in sera of 82.2% of patients with advanced GI cancer, which is an increase of 24.4% over the use of CEA antigen alone as a marker of disease. The measurement of both TAG-72 and CEA may improve the diagnosis of patients with GI malignant disease due to the apparent complementary association which exists between these tumor markers. Serum TAG-72 and CEA levels were monitored in 31 patients for varying lengths of time after resection of the carcinoma; 11 patients developed recurrent disease. Sera from nine of 11 (81.8%) of these patients had elevated TAG-72 levels and six of 11 (54.5%) had elevated CEA levels. Tumor marker elevations were observed either before (35 to 166 days) or at the time of diagnosis of recurrence. The elevation of one or both markers correlated with the clinical status in ten of 11 (90.9%) patients with recurrence. In addition, 20 patients who were clinically free of disease after more than 700 days' follow-up had normal serum levels of both TAG-72 and CEA. These findings suggest that the combined use of serum TAG-72 and CEA measurements may improve detection of recurrence in patients with GI cancer and may be useful in the postsurgical management of GI adenocarcinoma patients.     

Role of DAT‐SPECT in the diagnostic work up of Parkinsonism

The diagnosis of idiopathic Parkinson's disease (PD) can be achieved with high degrees of accuracy in cases with full expression of classical clinical features. However, diagnostic uncertainty remains in early disease with subtle or ambiguous signs. Functional imaging has been suggested to increase the diagnostic yield in parkinsonian syndromes with uncertain clinical classification. Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative Parkinsonism, is strongly related to decreases of dopamine transporter (DAT) density, which can be measured by single photon emission computed tomography (SPECT). The use of DAT‐SPECT facilitates the differential diagnosis in patients with isolated tremor symptoms not fulfilling PD or essential tremor criteria, drug‐induced, psychogenic and vascular Parkinsonism as well as dementia when associated with Parkinsonism. This review addresses the value of DAT‐SPECT in early differential diagnosis, and its potential as a screening tool for subjects at risk of developing PD as well as issues around the assessment of disease progression. © 2007 Movement Disorder Society     

An analytical solution for the SSFP signal in MRI.

Among previous analyses of the steady-state free-precession (SSFP) signal in rapid MRI, one treatment resulted in equations that require the evaluation of infinite binomial series. Here, an analytical solution is derived by a transformation into the power series expansion of the derivative of the inverse sine function, which is essentially a root. The treatment is extended to include higher-order signals. The results demonstrate the identity of the vastly different equations for the SSFP signals reported so far. Applications consist of the derivation of closed expressions for the signal in echo-shifted MRI and a corresponding analysis of TrueFISP sequences.     

Das kleinzellige Bronchialkarzinom – neue Entwicklungen nach ASCO 2007

Wiener Medizinische Wochenschrift - Aggressives Tumorwachstum, frühe Metastasierung und hohe Assoziation mit intensivem Nikotinkonsum sind die Charakteristika des kleinzelligen...     

Identification of N2 as a metabolite of acetylhydrazine in the rat

 In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [¹⁴C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [¹⁵N]-nitrogen and ¹⁴CO₂ exhalation, after the administration of [¹⁵N₂]-[¹⁴C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of ¹⁵N and ¹⁴N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB + cobalt(II) chloride (CoCl₂) (n=3 in each group). Time-dependent ¹⁵N₂ exhalation differed significantly between treatment groups (p<0.001). At 240 min, cumulative exhalation of ¹⁵N was 1.92±0.43% (mean±SE) of the dose in the control group, 2.53±0.23% in the PB group, and 1.00±0.15% in the PB+CoCl₂ group (p<0.05 compared to controls, p<0.01 compared to PB). Cumulative exhalation of ¹⁴CO₂ in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N₂ is a metabolite of AcHz. N₂ formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N₂-liberating process in vivo. Received: 14 March 1995/Accepted: 15 August 1995