Argon blocks the expression of locomotor sensitization to amphetamine through antagonism at the vesicular monoamine transporter-2 and mu-opioid receptor in the nucleus accumbens

We investigated the effects of the noble gas argon on the expression of locomotor sensitization to amphetamine and amphetamine-induced changes in dopamine release and mu-opioid neurotransmission in the nucleus accumbens. We found (1) argon blocked the increase in carrier-mediated dopamine release induced by amphetamine in brain slices, but, in contrast, potentiated the decrease in KCl-evoked dopamine release induced by amphetamine, thereby suggesting that argon inhibited the vesicular monoamine transporter-2; (2) argon blocked the expression of locomotor and mu-opioid neurotransmission sensitization induced by repeated amphetamine administration in a short-term model of sensitization in rats; (3) argon decreased the maximal number of binding sites and increased the dissociation constant of mu-receptors in membrane preparations, thereby indicating that argon is a mu-receptor antagonist; (4) argon blocked the expression of locomotor sensitization and context-dependent locomotor activity induced by repeated administration of amphetamine in a long-term model of sensitization. Taken together, these data indicate that argon could be of potential interest for treating drug addiction and dependence.     

Multidisciplinary evaluation of rat renal cell carcinoma

The rat renal cell carcinoma system as described by deVere White and Olsson in 1980 is used widely as a model for its human counterpart. The tumor arose spontaneously in a male Wistar Lewis rat and its behaviour has been shown to be stable during multiple passages. We have compared this tumor with the human renal cell carcinoma using a multidisciplinary approach. Light microscopy and electron microscopy showed a great resemblance of this rat tumor to a human renal cell carcinoma of the clear cell type with the ultrastructural presence of desmosomes. With the use of tissue specific antibodies against intermediate filament proteins, it could be shown that their expression is comparable to human renal cell carcinoma, i.e. coexpression of vimentin and different cytokeratins in the tumor cells. The cells could also be shown to contain cytokeratin 18. An aneuploid cell population in the tumor, expressing both vimentin and keratin, could be characterized by DNA flow cytometry in double labeling experiments. Comparison of normal and malignant rat kidney tissue by Northern blot analysis revealed increased levels of vimentin mRNA. In conclusion, this tumor model seems to have several histological and biological properties in common with the human renal tumor.     

Scintigraphic detection of pulmonary aspergillosis in rabbits with a radiolabeled leukotriene b4 antagonist.

Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we decided to test the imaging characteristics of this agent in a more clinically relevant model of pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the 111In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits with experimental pulmonary aspergillosis infection. The imaging characteristics of 111In-DPC11870 were compared with those of 67Ga-citrate, a radiopharmaceutical commonly used to detect pulmonary infections in patients. METHODS: Pulmonary aspergillosis was induced in the left lung of rabbits by intratracheal inoculation of 1 x 10(8) conidia of Aspergillus fumigatus. Three days after the inoculation, the rabbits received 111In-DPC11870 or 67Ga-citrate intravenously. Images were acquired at several time points up to 24 h after injection. RESULTS: Pulmonary aspergillosis was visualized with both agents. Images acquired after injection of 111In-DPC11870 showed uptake in the pulmonary lesions from 6 h after injection. Because of accumulation at the site of infection and clearance from the background, the images improved with time. Region-of-interest analysis at 24 h after injection revealed infected lung-to-normal lung ratios of 5.0 +/- 1.5 for 111In-DPC11870 and 2.9 +/- 0.6 for 67Ga-citrate. CONCLUSION: The radiolabeled LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary aspergillosis in rabbits. Images acquired at 24 h after injection of 111In-DPC11870 were superior to those obtained after injection of 67Ga-citrate.     

Extragonadal germ cell tumor invading the prostate

To our knowledge, only 3 patients with an extragonadal germ cell tumor of the prostate have been described in the literature until now. We here present a patient with a germ cell tumor arising in the retroperitoneum, invading the prostate, which was successfully treated by a combination of chemotherapy and nonmutilating surgery.     

Total anorectal reconstruction with a double dynamic graciloplasty after abdominoperineal reconstruction for low rectal cancer

PURPOSE: Total anorectal reconstruction with a double dynamic graciloplasty was performed after abdominoperineal reconstruction (APR) for low rectal cancer. In four patients an additional pouch was constructed to improve neorectal motility and capacity. The aim of this study was to evaluate the results in the first 20 patients and to report on the preliminary results of patients with an additional pouch. METHODS: Twenty patients with a mean age of 52 (range, 25–71) years and a rectal tumor at a mean of 3 (range, 0–5) cm from the anal verge were treated. In 14 patients the Miles resection, colon pull-through, and construction of a neosphincter were performed in one session. Six patients had the double graciloplasty at an average of 4.1 (range, 1.1–8.8) years after APR. In four patients a pouch was constructed with an isolated segment of distal ileum. RESULTS: After a mean follow-up of 24 (range, 1–60) months after APR, none of the patients developed local recurrence, whereas four patients developed distant metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients were still in training. Of these 15 patients, 8 patients were continent (53 percent), 2 patients were incontinent, and in 5 patients the perineal stoma was converted to an abdominal stoma. Failures were attributable to necrosis of the colon stump (n=2) and incontinence (n=3). At 26 weeks mean resting pressure was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation was 90 (SD, 46) mmHg at a mean of 35 (SD, 1.2) volts at 52 weeks. Mean defecation frequency was three times per day (range, 1–5). Of the eight patients who were continent, six used daily enemas. Mean time to postpone defecation was 11 (range, 0–30) minutes. CONCLUSION: In experienced hands, the double dynamic graciloplasty is an oncologically safe procedure that can have an acceptable functional outcome in a well-selected group of patients. However, to improve the outcome, further modifications will be necessary. So far, the addition of a pouch has not resulted in improved outcome. Supported by the Profileringsfonds of the Maastricht University Hospital, The Netherlands, and by the Stichting Fondsenwervingsactie Volksgezondheid, Amsterdam, The Netherlands. Read in part at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1995.     

Differences in aerodynamic characteristics of new and dysfunctional Provox®2 voice prostheses in vivo

Tracheoesophageal voice prostheses need to be replaced due to increased airflow resistance or retrograde leakage of fluid into the trachea as a consequence of biofilm formation. Previous in vitro studies show a change of aerodynamic features of biofilm covered voice prostheses after removal of the prostheses out of the patient. To assess these changes in an in situ situation, aerodynamic characteristics were measured within 45 patients at the beginning and at the end of the wearing process of the Provox 2 voice prosthesis. As a consequence, the influence of biofilm formation on aerodynamic characteristics can be evaluated. In the majority of cases, leakage through the prosthesis was the reason for replacement. No differences were found in the total flow, volume range and intratracheal pressure (ITP) of the voice prostheses measured. The airflow resistance of biofilm covered prostheses was significantly reduced compared to new clean prostheses. However, no correlation was found between the extent of biofilm and the different aerodynamic features measured. Biofilm formation on the Provox 2 is responsible for both reduction in airflow resistance and leakage through the prosthesis by deterioration of the silicone rubber material.     

Antioxidant defence during cardiopulmonary bypass surgery.

OBJECTIVE: Cardiac surgery may lead to severe oxidative stress due to formation of oxidation products generated during ischemia and reperfusion. We investigated to which extent oxidative stress influences a number of endogenous antioxidants and markers of cellular activation. METHODS: At six time points blood was withdrawn from patients undergoing coronary artery bypass grafting, using the on-pump procedure. RESULTS: Both glutathione peroxidase and superoxide dismutase show a gradual and strong increase in activity during surgery (40 and 30%, respectively), returning to baseline values 24 h after surgery. The total antioxidant capacity has a maximum increase of 60%. Markers of cellular activation, such as eosinophil cationic protein and tryptase also increase during the procedure. CONCLUSION: Cardiac surgery results in systemic inflammation accompanied or caused by severe oxidative stress. The human body has a strong innate oxidative defence screen, which is probably not sufficient to fully compensate for the total amount of oxidative damage.