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Background. Clinical and/or laboratory signs of systemic inflammation occur frequently in patients undergoing long-term haemodialysis. It is likely, therefore, that a compensatory release of endogenous anti-inflammatory molecules occurs to limit host reactions. The aim of the present research was to determine if the potent anti-inflammatory peptide α-melanocyte-stimulating hormone (α-MSH), a pro-opiomelanocortin derivative, is increased in plasma of haemodialysis patients. Because endotoxin and cytokines induce α-MSH in vivo and in vitro, we also measured plasma concentrations of endotoxin, interleukin-6 (IL-6), and tumour necrosis factor α (TNF-α), and the two circulating products of activated monocytes, nitric oxide (NO) and neopterin.
Methods. Thirty-five chronic haemodialysis patients, 20 patients with chronic renal failure not yet on dialysis, and 35 normal controls were included in the study. In the haemodialysis group, blood samples were obtained before and at the end of a dialysis session. Plasma α-MSH was measured using a double antibody radioimmunoassay, and IL-6, TNF-α, and neopterin using specific enzyme-linked immunosorbent assays. Plasma nitrites were determined by a colorimetric method, and endotoxin with the quantitative chromogenic LAL (limulus amoebocyte lysate) method.
Results. Mean plasma α-MSH was higher in haemodialysis patients than in control subjects, with the peptide concentrations being particularly elevated in dialysed patients with detectable endotoxin. High α-MSH concentrations were observed in the pre-dialysis samples, with no substantial change at the end of the dialysis session. Plasma concentrations of IL-6, TNF-α, neopterin, and NO were generally elevated in chronic haemodialysis patients and there was a negative correlation between circulating α-MSH and IL-6. In patients with renal failure not yet on dialysis, mean plasma α-MSH was similar to that of normal subjects.
Conclusions. α-MSH is increased in the circulation of chronic haemodialysis patients and particularly so in case of detectable endotoxaemia. Reduction of renal clearance is unlikely to contribute to the observed rise of the peptide because α-MSH concentration is not increased in patients with chronic renal failure who are not yet on dialysis. It is likely that dialysis-associated endotoxaemia, directly and/or through cytokine release, enhances the production of the anti-inflammatory mediator α-MSH that limits host reactions.

Clinical and/or laboratory signs of systemic inflammation occur frequently in patients undergoing long-term haemodialysis. It is likely, therefore, that a compensatory release of endogenous anti-inflammatory molecules occurs to limit host reactions. The aim of the present research was to determine if the potent anti-inflammatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin derivative, is increased in plasma of haemodialysis patients. Because endotoxin and cytokines induce alpha-MSH in vivo and in vitro, we also measured plasma concentrations of endotoxin, interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), and the two circulating products of activated monocytes, nitric oxide (NO) and neopterin.

The regulation of cholinergic markers by exogenous nerve growth factor (NGF) and/or monosialoganglioside GM1 (GM1) treatment was examined in various brain areas of unilaterally decorticated rats, with particular emphasis on the basal forebrain system. Treatment of decorticated rats, i.c.v. via a minipump, with various doses of NGF or GM1 for a period of 7 days prevented the lesion-induced decline in nucleus basalis magnocellularis choline acetyltransferase (ChAT) activity in a dose-dependent manner. These treatments also stimulated cortical ChAT activity as well as high-affinity choline uptake. Cholinergic markers in other brain areas studied were unaffected by the lesion or these treatments, except in the striatum in which exogenous NGF but not GM1 caused dose-dependent increases in ChAT activity and high-affinity choline uptake. Glutamic acid decarboxylase activity was unaffected by the lesion or treatments in all brain areas studied. Cotreatment of lesioned rats with GM1 did not affect NGF potency but did increase its maximal efficacy in the nucleus basalis magnocellularis and cortex, but not in the striatum. Treatment of cortically lesioned rats with maximal doses of GM1 and/or NGF did not differentially alter "soluble" or "membrane bound" forms of ChAT. In addition, choline uptake kinetic parameters also were affected similarly by these agents as evidenced by augmented Vmax and unaltered Km values. Distinct effects of NGF and GM1 were observed, however, in regard to the delay possible in treatment time onset. No significant alteration in NGF receptor density or affinity were noted in the remaining cortex of GM1-treated decorticated rats, suggesting that GM1 interacts with an alternative facet of NGF signal transduction to potentiate NGF effects on cholinergic markers.

Nello studio della patologia non tumorale del rachide la Risonanza Magnetica svolge un ruolo fondamentale non solo nel rilievo diagnostico ma anche nel seguire la sequenza dei normali processi d'invecchiamento della colonna vertebrale. Nelle malformazioni la R.M. restituirà la visione unitaria di sistema multicompartimentale alle strutture ossee e nervose, svincolandolo da uno studio singolo di struttura con successivo meccanismo di integrazione artificiale. Nei traumi permetterà il rilievo non solo della patologia in atto, ma anche di una ipotesi in prospettiva delle chances di recupero. Nelle malattie flogistiche e infiammatorie la R.M. permetterà uno studio accurato dell'estensione del processo e della progressione con coinvolgimento delle strutture vicine. Nei processi degenerativi infine la R.M. permetterà di ipotizzare il limite tra i normali processi di invecchiamento e la patologia e seguirà le situazioni potenzialmente patogene nel loro aggravamento nella loro fase di suscettibilità chirurgica. Per tutti questi obiettivi l'utilizzo di impianti affidabili, di studio dei tempi di rilassamento dei tessuti in prospettiva di opportune sequenze di impulsi, di applicazioni di tecniche di fast scanning, importanti non solo per il risparmio di tempo ma anche per la capacità diagnostica tutta in costruzione, sono e saranno campi di ricerca.Inoltre l'introduzione dei mezzi di contrasto paramagnetici in RM ha ulteriormente amplificato la sfida nelle ricerche.

The prevention of the decrease of choline acetyltransferase (ChAT) enzymatic activity was achieved by applying GM1 in an animal model for studying retrograde degenerations of cholinergic neurons. Devascularizing lesions of the rat cortex led to a significant decrease in activity of ChAT in the nucleus basalis magnocellularis (NBM), but this decrease was effectively prevented by GM1 administration either centrally or locally in a microencapsulated form. Compared with the relatively large dose of GM1 which has to be given when the drug is administered, i.p. microencapsulated GM1 applied locally and directly over the lesioned cortical surface seems to be effective in much lower doses.

In the present study we report the isolation of five iridoids and bis-iridoids identified as secologanin (I), swerosidic acid (II), secoxyloganin (III), sylvestroside I (IV) and sylvestroside III (V) from Acicarpha tribuloides Juss. (Calyceraceae). Also, the pharmacological profile of the extracts (Petroleum ether, CHCl 3, CHCl 3 /MeOH (9:1), MeOH and n-BuOH) from A. tribuloides was studied both in vivo and in vitro experiments. The in vivo experiments indicate that CHCl 3 /MeOH, MeOH and n-BuOH (100, 50 and 10 mg/kg/po) induce a significative analgesic effect in mice whereas CHCl 3 and petroleum ether extracts were inactive. In the in vitro experiments the extracts showed a similar activity because CHCl 3 /MeOH, MeOH and n-BuOH (500,250 and 125 µg/ml) were able to reduce the electrically induced contractions of guinea-pig ileum whereas CHCl 3 and petroleum ether extracts did not. As the active extracts contain iridoids, the pharmacological effects observed appear to depend on these structures.

This study examined the behavioral effects of maximal doses of exogenous NGF and/or GM1 when given intracerebroventricularly to adult rats with unilateral cortical lesions. In addition, the long-term effects of these agents on choline acetyltransferase (ChAT), glutamic acid decarboxylase (GAD) activity, and choline uptake, as well as on ChAT and NGF receptor (p75NGFR) immunoreactivity in various brain regions, were also investigated. When retested in passive avoidance and Morris water maze tasks, 30 days postlesion (i.e., 2 weeks after termination of treatment), decorticated vehicle-treated rats showed retention and reacquisition deficits which were equally attenuated by NGF (6 μg/day, 14 days) or NGF + GM1 (750 μg/day, 14 days) treatment. By contrast, lesioned animals which received GM1 alone only showed improved reacquisition of the two tasks. After behavioral testing (52 days postlesion) lesioned vehicle-treated animals had decreased ChAT activity in the ipsilateral nucleus basalis magnocellularis (NBM) but not in other subcortical brain areas examined. Neuronal loss was observed only in the ventrolateral nucleus of the ipsilateral dorsal thalamus. However, using quantitative image analysis a significant shrinkage of ChAT immunoreactive (IR) and p75NGFR-IR NBM neurons as well as a decrease in their neuritic network was noted, particularly in the mid portion of the NBM. GM1 and NGF equally prevented these deficits in the NBM and, furthermore, enhanced ChAT activity and choline uptake in the remaining cortex ipsilateral to the lesion site. These alterations in NBM and cortical cholinergic markers were even more augmented in rats which received both NGF and GM1 treatment. By contrast, the noted NGF-induced increase in striatal ChAT activity was not further increased by concomitant GM1 treatment. GAD activity in all brain areas examined was unaltered by the lesion or any of the treatments and the apparent thalamic neuronal retrograde degeneration was not prevented by any of the treatments. It is concluded that GM1 or NGF treatment can distinctly affect performance of cortically lesioned rats in passive avoidance and Morris water maze tasks despite their equal ability to serve as long-term neuroprotective agents for the basalo-cortical cholinergic pathway.

In this study light and EM quantitative analysis were used to examine whether exogenous nerve growth factor (NGF) could affect terminal fields and synaptic connections in the adult rat brain in vivo. Adult rats received, immediately after unilateral decortication, 2.5S NGF (12 micrograms/day) or vehicle intracerebroventricularly for 7 days. Thirty days after the lesion cholinergic fiber length was quantified, using image analysis, in the remaining cortical area adjacent to the lesion site in each animal. Rats that had received vehicle showed a significantly reduced cortical choline acetyl-transferase-immunoreactive fiber network in the remaining cortex when compared with control animals. By contrast, the network in lesioned rats that had received 2.5S NGF was not different from control animals. Furthermore, the number of cortical choline acetyltransferase-immunoreactive varicosities, which decreased in vehicle-treated lesioned rats, significantly increased above control in lesioned rats that had received 2.5S NGF. At the ultrastructural level, 30 days after the lesion, animals that had received vehicle showed shrunken cholinergic boutons in cortical layer V and fewer synapses compared with control animals. Exogenous NGF, administered to lesioned rats, increased to supernormal levels both size of cholinergic boutons and number of synaptic contacts. These parameters were unaltered in unlesioned rats treated with NGF. This study demonstrates that exogenous NGF can cause significant compensatory changes in terminal fields and synaptic connections in the adult fully differentiated central nervous system.

The effects of nerve growth factor beta (beta-NGF) and ganglioside GM1 on forebrain cholinergic neurons were examined in vivo and in vitro. Following unilateral decortication of rats, GM1 (5 mg/kg per day) administered intracerebroventricularly could protect forebrain cholinergic neurons of the nucleus basalis magnocellularis from retrograde degeneration in a manner comparable to beta-NGF. Administered in combination with beta-NGF, GM1 produced a significant increase in choline acetyltransferase activity in the nucleus basalis magnocellularis and remaining cortex ipsilateral to the lesion. Concentrations of GM1 that were ineffective when administered alone in this lesion model, when given with beta-NGF, potentiated beta-NGF effects in both of the above brain areas. In dissociated septal cells in vitro, an increase in choline acetyltransferase activity was noted at beta-NGF concentrations as low as 0.1 pM and reached a plateau at 1 nM. A moderate (up to 35%) stimulation of choline acetyltransferase activity was observed with 10 microM GM1. The application of beta-NGF in combination with 10 microM GM1 or 0.1 microM GM1, a concentration that is ineffective in these cultures, produced a much greater increase in choline acetyltransferase activity than did beta-NGF alone. These observations support the idea that exogenously applied gangliosides can elicit trophic responses in cholinergic neurons of the central nervous system. That GM1 increases and even potentiates beta-NGF effects suggests that some of the trophic actions of this compound may be mediated through endogenous trophic factors.

The effect of indole alkaloids from Sickingia williamsiiStandi. (Rubiaceae) on the effects of morphine withdrawal have been examined in-vitro.All the indole alkaloids isolated from S. williamsii(10−4, 5 ×10−5and 10−5m) significantly and in a concentration-dependent manner reduced the effects of morphine withdrawal on the guinea-pig ileum.The results suggest that these alkaloids might be potential anti-addictive agents.

The effect of indole alkaloids from Sickingia williamsiiStandi. (Rubiaceae) on the effects of morphine withdrawal have been examined in‐vitro.

I linfomi del sistema nervoso centrale, a lungo eteroplasie intracraniche rare (1–2%) sono in continuo aumento percentuale in relazione con l'immunodepressione virale dell' AIDS (6% dei pazienti, 3% in età pediatrica), così come con quella iatrogena.Tipiche dei linfomi AIDS l'associazione con l'EB virus, l'elevata malignità, la scarsa risposta alla terapia, la localizzazione (SNC, midollo, intestino, cute, anoretto).Oggi tali tumori sono riscontrati in tutte le età (60 anni è la decade di presentazione tipica negli immunocompetenti). Le forme intracraniche, soprattutto B (80%), sono l'1% dei Non-Hodgkin, e dovrebbero essere considerate in realtà secondarie, dal punto di vista fisiopatologico, anche nei casi in cui l'esordio riguardi il SNC. Dal 20 al 40% dei casi sono forme multiple.Il ruolo giocato dall'Imaging deve essere considerato importante, poiché, nonostante le frequenti recidive a breve termine (la sopravvivenza media dalla diagnosi supera di poco l'anno, ed è minore nell'AIDS), queste forme rispondono, quando correttamente inquadrate, assai bene alle alte dosi di cortisonici (nel 40% dei soggetti trattati, già in 24 ore, per linfolisi e ripristino della b.e.e.) così come alla radioterapia.Nella patogenesi sono invocati differenti meccanismi di interconnessione tra neoplasie e agenti virali.La sede preferenziale è sopratentoriale in regione dei nuclei della base o comunque in strutture in cui la componente prevalente è la sostanza bianca.L'estensione dell'edema è incongrua rispetto all'entità della lesione, in ragione della esigua neoangiogenesi indotta.Queste masse hanno margini relativamente ben definiti solo macroscopicamente, con ben maggiore infiltrazione all'istologia; foci di rammollimento necrotico o emorragico sono rari nei pazienti AIDS.All'istologia la zona centrale di cellularità elevata, più rarefatta in periferia, mostra un caratteristico aspetto a “bulbo di cipolla” della trama reticolare.Queste neoplasie si localizzano a livello degli “involucri” cerebrali: sedi caratteristiche sono infatti le leptomeningi e le aree lungo lo spazio subependimal (40–50%), aree di coinvolgimento rese manifeste dalla impregnazione del m.d.c.L'impregnazione lungo le pareti ventricolari suggerisce la diagnosi specie se le immagini RM rivelano l'ulteriore diffusione delle localizzazione leptomeningee lungo gli spazi perivascolari di Virchow Robin.Questi tumori metastatizzano per via ematica, determinando la comparsa di lesioni parenchimali, leptomeningee e meningo-durali.In sede meningo-durale un notevole infiltrato linfomatoso può assumere aspetto a lente biconvessa.Non esistono significative differenze di imaging tra forme linfomatose primitive e secondarie del S.N.C.La TC dimostra lesioni solide singole o multiple, rotondeggianti, isodense al parenchima, (nel 20% dei casi iperdense) con quasi costante accentuazione dopo m.d.c., raramente solo periferica.La RM dimostra isoiperintensità in T1, modesto incremento in DP e ipointensità rispetto alla grigia in T2, da scarso citoplasma delle cellule componenti.L'impregnazione è unicamente da alterazione della barriera emato-encefalica (scarsa la componente neovascolare).