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.     

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.     

How does a Belgian health care provider deal with a request for emergency contraception?

OBJECTIVE: To evaluate how Belgian health care providers deal with a request for emergency contraception. METHOD: In 2002-2003 we conducted 12 focus groups with pharmacists, general practitioners and school physicians. A skilled moderator accompanied by an observer conducted the focus groups using a semi-structured screenplay. RESULTS: All these health care providers agree with the free access to emergency contraception (EC), but experience considerable frustration with regard to the practical aspects and the legal framework. General practitioners (GPs) claim to spend a lot of time on requests for EC and they are concerned about the quality of the counselling provided in pharmacies. Pharmacists are creative when giving counselling in the pharmacy, but there is, nevertheless, a problem with a lack of privacy. School physicians are frustrated that there is no legal possibility to respond to a request for EC when they feel they are ideally placed to advise adolescents. CONCLUSION: The over-the-counter sale of EC offers women better access, but many barriers still interfere with optimal care. Pharmacists experience a lack of skills to communicate with adolescents and a lack of privacy to give counselling. GPs have good intentions, but are confronted with a lack of willingness on the part of the patients and also financial barriers. School physicians want more possibilities to help adolescents.     

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.     

Psychological aspects of female urinary incontinence in general practice.

The aim of this study was to determine whether urge incontinence was associated with a higher prevalence of psychological symptoms than other types of incontinence. The psychological aspects of 110 women presenting with urinary incontinence in general practice were assessed by means of standardised questionnaires and medical history-taking. The results showed no difference in psychological characteristics between patients with urge incontinence and those with other types of incontinence. These findings were contrary to the conclusions of almost all other studies based on populations selected for specialist care. It was concluded that in general practice the psychological approach to urinary incontinence depends more on the individual needs of the patient than specifically on the type of incontinence.     

Impaired immune response by isoniazid treatment during intravesical BCG administration in the guinea pig.

At present, isoniazid (INH) is being used prophylactically to reduce the side effects of intravesical BCG therapy for superficial bladder cancer, although it is not clear whether or not this reduces the antitumor efficacy of BCG. In this study the impact of INH treatment on the immune response after repeated intravesical BCG administration was investigated in guinea pigs. INH was given on the 3 days around each BCG instillation. We found that the administration of INH severely impaired the immunological effects of BCG. The induction of mononuclear cell infiltration in the bladder wall was reduced. Enlargement of the regional lymph nodes (weight and number of cells), and increase of MHC Class II expression on the lymph node cells, normally observed after intravesical BCG administration, were inhibited by INH. Systemic immunity, measured by the DTH reaction in the skin to PPD, was also diminished due to the combined treatment of BCG with INH. When INH was administered during the last 4 of 6 BCG instillations, the immune response to BCG was still impaired. A five-fold increase of the dose of BCG did not overcome the effect of INH. INH probably did not exert a direct suppression of the immune system of the guinea pig as the DNCB skin reactivity was not influenced. Although INH concentrations in the urine were high at the onset of the instillation, in vitro experiments indicated that the effect of INH may not be caused by killing of the BCG organisms shortly after application in the bladder. In conclusion, our data in guinea pigs suggest that the use of INH may impair the immune response to intravesical BCG. As this response may be important for the antitumor effect of BCG, urologists should be cautious with the prophylactic use of INH. The influence on the antitumor efficacy is now investigated in man.