Treatment frequency and efficiency in hemodiafiltration.

BACKGROUND: One of the main objectives of dialysis is uremic retention product elimination. Efficiency of dialysis modalities varies both regarding the range of solutes removed and the extent of such removal. We analyzed plasma (or blood) concentrations of marker solutes in intermittent treatment schedules using hemodiafiltration (HDF). METHODS: Elimination and rebound of uremic solutes were measured in 10 patients (77 ± 12 kg, 66.5 ± 9.2 years) treated with postdilution HDF in one 4-hour treatment and in two 2-hour treatments on consecutive days (Polyflux 2.1 m(2), QB 451 ± 53 ml/min, QD 598 ± 13 ml/min). Blood urea, creatinine, phosphate, ß2-microglobulin, complement factor D and advanced glycation end products were analyzed before, during and after HDF for 24-48 h. RESULTS: Applying two 2-hour HDF treatments on consecutive days resulted in significantly lower plasma (or blood) levels of urea, creatinine, phosphate, ß2-microglobulin, and advanced glycation end products after 48 h than using one 4-hour session. CONCLUSIONS: Increased treatment frequency could further optimize blood purification in HDF therapy.

Continuous versus pulsatile administration of rotigotine in 6-OHDA-lesioned rats: contralateral rotations and abnormal involuntary movements.

Sustained drug delivery providing continuous dopaminergic stimulation is thought to prevent or delay the induction of motor complications (dyskinesia) in Parkinson's disease, whereas pulsatile administration is supposed to promote them. This study investigated the inducibility of sensitization and abnormal involuntary movements (AIMs), comparing continuous and pulsatile administration of rotigotine with pulsatile administration of 3,4-dihydroxy-L-phenylalanine (L-DOPA) for reference. Rats were unilaterally lesioned with 6 hydroxydopamine (6-OHDA). For pulsatile administration, L-DOPA-methylester (10 mg/kg L-DOPA i.p.) or rotigotine (1 mg/kg i.p.) were administered once or twice daily. For continuous administration, a slow release formulation of rotigotine was injected s.c. at a dose of 1 mg/kg every 48 h (experiment I) or every 24 h (experiment II). Pulsatile administration of rotigotine and L-DOPA caused contraversive rotations increasing progressively upon each successive treatment. AIMs started to occur after the second administration of L-DOPA but hardly after pulsatile rotigotine. Continuous rotigotine increased rotations, which reached a plateau after the second administration. No AIMs were observed under continuous administration. The continuous administration of rotigotine did not induce sensitization or AIMs, suggesting that continuous stimulation of dopaminergic receptors by rotigotine has no propensity to induce dyskinesia in this experimental model.

3,4-Methylenedioxymethamphetamine and naloxone in rat rotational behaviour and open field.

It has recently been shown that 3,4-Methylenedioxymethamphetamine (MDMA) has an anti-parkinsonian effect in rodent models of Parkinson's disease. The mechanism of this anti-parkinsonian action is unknown. Opioids have been suggested to play a role in MDMA-induced behaviour. We therefore investigated MDMA and naloxone in the rat rotational behavioural model. Male Sprague-Dawley rats were lesioned unilaterally with 6-hydroxydopamine at the medial forebrain bundle. Administration of R/S-MDMA (5 mg/kg, s.c.) produced ipsilateral rotations. Naloxone (2, 5, 10 mg/kg, s.c.) did not produce rotations on its own but reduced the number of MDMA-induced ipsilateral rotations. This effect was not dose-dependent. In contrast to reports on mice, in unlesioned animals, naloxone (10 mg/kg, s.c.) did not block MDMA (5 mg/kg, s.c.)-induced hyperactivity in an open field in our experiment. It is concluded that endogenous opioids play a role in MDMA's action in the rat rotational behavioural model.

3,4-Methylenedioxymethamphetamine counteracts akinesia enantioselectively in rat rotational behavior and catalepsy.

We have shown recently that 3,4-methylenedioxymethamphetamine (MDMA) has symptomatic antiparkinsonian activity in rodent models of Parkinson's disease. In search of its mechanism of action, we further investigated the enantiomers of MDMA in the rotational behavioral model and catalepsy test. Catalepsy testing was done in drug-naive unlesioned animals. The parkinsonian symptoms rigor and akinesia (i.e., catalepsy) were induced by intraperitoneal administration of haloperidol 0.5 mg/kg and measured repeatedly as descent latency from a horizontal bar and a vertical grid. MDMA and both its enantiomers were effective in counteracting haloperidol-induced catalepsy, but if given as racemic, the effects were more pronounced than with the enantiomers. For testing of rotational behavior, male Sprague Dawley rats were lesioned unilaterally with 6-hydroxydopamine (6-OHDA) at the medial forebrain bundle. Administration of S-MDMA (5 mg/kg) produced ipsilateral rotations. R-MDMA was far less effective in inducing ipsilateral rotations in 6-OHDA unilaterally lesioned rats, but when S-MDMA was given additionally rotations immediately increased. Regarding their overall antiparkinsonian effects, the S-enantiomer of MDMA was more effective than its R-congener. R-MDMA was able to increase the actions of S-MDMA.