Blunted renal dopaminergic system activity in puromycin aminonucleoside-induced nephrotic syndrome.

BACKGROUND: A primary tubular sodium handling abnormality has been implicated in the edema formation of nephrotic syndrome. Dopamine synthesized by renal proximal tubules behaves as an endogenous natriuretic hormone by activating D(1)-like receptors as a paracrine/autocrine substance. METHODS: We examined the time courses of the urinary excretion of sodium, protein and dopamine in puromycin aminonucleoside (PAN)-treated and control rats. The rats were sacrificed during greatest sodium retention (day 7) as well as during negative sodium balance (day 14) for the evaluation of renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine. Also, the influence of volume expansion (VE) and the effects of the D(1)-like agonist fenoldopam (10 microg/kg bw/min) on natriuresis and on proximal tubular Na(+),K(+)-ATPase activity were examined on day 7. RESULTS: The daily urinary excretion of dopamine was decreased in PAN-treated rats, from day 5 and beyond. This was accompanied by a marked decrease in the renal AADC activity, on days 7 and 14. During VE, the fenoldopam-induced decrease in proximal tubular Na(+),K(+)-ATPase activity was more pronounced in PAN-treated rats than in controls. However, the urinary sodium excretion during fenoldopam infusion was markedly increased in control rats but was not altered in PAN-treated animals. CONCLUSION: PAN nephrosis is associated with a blunted renal dopaminergic system activity which may contribute to enhance the proximal tubular Na(+),K(+)-ATPase activity. However, the lack of renal dopamine appears not to be related with the overall renal sodium retention in a state of proteinuria.     

Some central effects of brofaromine given repeatedly are phase-dependent

Effects of the MAO-A-inhibitor brofaromine (BRO), 10 mg/kg po after repeated (twice daily for 14 days) administration on the spontaneous behavior (exploratory and basal locomotor activities) and the exploratory activity modified by methoxamine, clonidine and d-amphetamine in male Wistar rats were studied in both light and dark phases of a diurnal cycle (L: 0700-1900 h). After single administration BRO in the light phase had no effects. In the dark phase BRO decreased the exploration (62% of control, p less than 0.01), increased the clonidine-evoked hypoactivity and amphetamine-evoked hyperactivity. The L-D differences occurred also after repeated administration. BRO in the light phase did not influence the exploration, decreased basal locomotor activity, did not change methoxamine and clonidine action and potentiated the action of amphetamine. In the dark phase, however, it did not influence the exploration and basal locomotor activity, intensified the methoxamine effect, and did not change the clonidine and amphetamine actions. The results demonstrate that the effects of BRO on behavior in rats: 1) differ from the effects caused by other antidepressants which are not MAO inhibitors; 2) are phase-dependent after both single and repeated administration.     

A clinical trial on the prevention of catheter-related sepsis using a new hub model.

BACKGROUND: Catheter hub contamination is being increasingly recognized as a source of catheter-related sepsis. The authors have investigated the efficacy of a new hub design in preventing endoluminal catheter contamination and catheter-related sepsis arising at the hub. METHODS: Adult surgical and intensive care patients requiring a subclavian catheter for at least 1 week were randomly assigned to receive catheters with standard connectors (control group, n=73) or equipped with a new hub model (new hub group, n=78). Skin, catheter tip, and hub cultures were performed at the time the catheter was withdrawn because therapy was terminated or because of suspicion of sepsis, in which case peripheral blood cultures were taken. RESULTS: Of the 151 patients included, 15 (10%) developed catheter-related sepsis. Catheters were more often withdrawn because suspicion of infection in the control group (42 vs. 19%, p<0.005). Catheter sepsis rate was higher in the control group (16 vs. 4%, p<0.01) because of the low rate of catheter sepsis arising at the hub observed in the new hub group (1 vs. 11%, p<0.01). The prevalence of culture-positive catheter hubs without associated bacteremia (colonization) was higher in the control group (18 vs. 5%, P<0.03). CONCLUSIONS: A new catheter hub has proved to be useful in preventing endoluminal bacterial colonization and catheter-related sepsis in subclavian lines inserted for a mean of 2 weeks.     

The ejaculatory behavior of sexually sluggish male rats treated with (-)deprenyl, apomorphine, bromocriptine and amphetamine

Bromocriptine (0.5 mg/kg) and apomorphine (0.03 mg/kg) exert moderate aphrodisiac effect in sexually sluggish rats. This effect appears rapidly and reaches its peak within 24 h. Amphetamine (2 mg/kg) acts similarly but with a more rapid onset and offset of the effect. A single dose of (-)deprenyl, a selective inhibitor of MAO-B, exerts a much more potent effect in this test.     

Melatonin modifies the spontaneous multiunit activity recorded in several brain nuclei of freely behaving rats.

Melatonin, a pineal hormone, released photoperiodically, was administered systemically in rats, previously implanted with semimicroelectrodes into six different brain structures. The multiunit electrical activity of these structures was recorded for 10 min before and 60 min after melatonin administration in unanesthetized, freely moving rats. Different melatonin doses (100, 200, 500, and 1000 micrograms/kg) produced changes in the electrical activity of all tested structures. However, amygdala, rostral hypothalamus and mesencephalic reticular formation showed the most important changes. The main effect induced by melatonin was a dose-related decrease of the spontaneous electrical activity. The significance of these effects is discussed within the context of the behavioral and endocrinological effects of melatonin.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.     

Occupation and bladder cancer in Spain: a multi-centre case-control study

A case-control study on bladder cancer was carried out in four regions of Spain. The study included 497 cases (438 males and 59 females), 583 hospital controls and 530 population controls matched by sex, age and residence. The present paper reports the results of the analyses on occupational history. Among men, an increased risk of bladder cancer was found for textile workers (OR = 1.97, 95% CL 1.2-3.3), mechanics and maintenance workers (OR = 1.86, 95% CL 1.2-2.8), workers in the printing industry (OR = 2.06, 95% CL 1.0-4.3) and for managers (OR = 2.03, 95% CL 1.2-3.5). The risk was highest among those first employed in the textile industry before the age of 25 and prior to 1960. Among mechanics the risk was highest for those who started after the age of 25 and later than 1960. The OR for smokers who had also been employed in one of the high risk occupations was 7.82 (95% CL 4.4-14.0) which is compatible with a multiplicative effect of joint exposure to tobacco and occupational hazards.