L-deprenyl fails to protect mesencephalic dopamine neurons and PC12 cells from the neurotoxic effect of 1-methyl-4-phenylpyridinium ion.

L-Deprenyl, a monoamine oxidase (MAO)-B inhibitor, appears to slow down the progression of Parkinson's disease. While inhibition of MAO-B activity can account for some of the effects of this substance, the basis by which L-deprenyl slows the progression of the disease remains controversial. In recent years, a new mechanism of action has emerged that may explain the ability of L-deprenyl to increase neuronal survival. L-deprenyl has been reported to modify gene expression and protein synthesis in astrocytes and PC12 cells. In this study, we tested the ability of L-deprenyl to protect mouse mesencephalic cells from the toxicity of the 1-methyl-4-phenyl pyridinium ion (MPP+). We exposed mouse mesencephalic cell cultures to L-deprenyl (10 microM) and, 24 h later, to MPP+ (2.5 microM). On the fifth day after L-deprenyl and MPP+ exposition, cells were washed free of drugs, and the following day they were tested for dopamine uptake, intracellular dopamine content and tyrosine hydroxylase immunoreactivity. The experiments were performed either in the presence or in the absence of glia. It was found that L-deprenyl pretreatment failed to achieve any protection against MPP+ toxicity. The fall in dopamine uptake and intracellular dopamine content, and the diminution of tyrosine hydroxylase immunoreactivity observed in cells pretreated with L-deprenyl and then given MPP+ were not significantly different from the values observed in cells treated with MPP+ alone. Additional experiments performed in PC12 cells, confirmed the failure of L-deprenyl to abolish the toxicity of MPP+. Our data seem to be at variance with previous reports demonstrating that the MAO-B inhibitor L-deprenyl protects dopaminergic neurons against MPP+ toxicity [12,20]; furthermore they do not support alternative mechanisms of action of L-deprenyl against MPP+ toxicity.

Laparoscopic cholecystectomy in a patient with mitochondrial myopathy.

The authors report a 27-year-old woman with mitochondrial myopathy and respiratory failure requiring nasal-CPAP administration who successfully underwent laparoscopic cholecystectomy for chronic cholecystitis. The hypothesis that minimally invasive surgery results in less operative stress is truly substantiated by the experience with laparoscopy in such patients with high risk of perioperative and postoperative complications.

Adenocarcinoma of the duodenal bulb in a young coeliac woman.

Coeliac sprue patients display an increased frequency of malignant neoplasms of the gastrointestinal tract. These neoplasms are chiefly represented by lymphomas, occurring in patients over 50. We describe the onset of a duodenal adenocarcinoma in a young woman with coeliac disease and discuss the unusual features of this case.

Striatal MPP+ levels do not necessarily correlate with striatal dopamine levels after MPTP treatment in mice.

The present study offers confirmation of the fact that an MAO-B inhibitor, (-) deprenyl and a DA uptake blocker, GBR-12909, prevent MPTP-induced striatal DA decrease. This protective effect is accompanied by an almost complete prevention of MPP+ production induced by (-) deprenyl and an accelerated MPP+ clearance induced by GBR-12909 within the striatum. Similarly, the MPTP toxicity enhancers, DDC and acetaldehyde, both increase striatal MPP+ levels, as previously reported. On the contrary, the treatment with MK 801, although uneffective in preventing the long-term MPTP-induced striatal DA decrease, causes an increase in the striatal amount of MPP+. In a similar way, the administration of nicotine in combination with MPTP produces a significant increase in the levels of striatal MPP+, which does not elicit any effect on striatal DA. The effect of clonidine is consistent with these results and in sharp contrast with the current belief that a direct relationship exists between striatal MPP+ concentrations and the degree of MPTP-induced depletion of striatal DA. In this study, using different treatments, we failed to confirm the correlation between MPP+ striatal levels and dopaminergic lesions after MPTP administration in mice. We suggest that this correlation is not a rule and exceptions may depend on a different compartimentalization of the toxic metabolite.

Is lithium able to reverse neurological damage induced by vinca alkaloids? (Short communication).

Lithium (Li) actively antagonises the inhibiting action of vinca alkaloids on human leukocyte chemotaxis; it proved to be related to the activation of microtubular system, possibly mediated by its inhibiting effect on cyclic AMP. Vinca alkaloids induce peripheral neuropathy and muscle damage. The molecular basis of this neurotoxicity has not been fully explained, but a possible role of neurofibrillary degeneration has been reported. We studied both in animals and in humans, whether Li is able to antagonise vinca alkaloid neurotoxicity.

Prolonged manometric investigation of the colon in research on chronic constipation.

We studied the whole colonic motility for 24 hours in controls and in constipated patients. In the patient group we found a significant reduction in the colonic mass movements (6.1 +/- 0.9 vs 2.6 +/- 0.7 controls vs patients, respectively). The constipated patients showed a reduction of the colonic motor activity after the ingestion of a standard meal. Moreover, they showed, compared with controls, a significant reduction of postprandial mass movements. On the other hand we were not able to find the so-called rectal motor complex described by others. In conclusion, we believe that prolonged colonic manometry would become an important step when evaluating the pathophysiology of constipated patients, particularly of those not responding to standard treatment.

Giardia lamblia infestation reveals underlying Whipple's disease in a patient with longstanding constipation.

Whipple's disease is an uncommon disorder, generally associated with gastrointestinal symptoms; of these, diarrhea is a common feature. We report a case of Whipple's disease associated with chronic constipation which was not diagnosed until after Giardia lamblia infestation had caused diarrhea. To the best of our knowledge this association has not previously been reported. The clinical, laboratory, endoscopic, and manometric aspects are described and discussed.

Abnormal gastrointestinal motility in patients with celiac sprue.

No study to date has objectively investigated whether the motor behavior of the small bowel is abnormal in celiac sprue. The purpose of this study was to systematically address this topic by means of intraluminal pressure recordings in a series of such patients. Sixteen subjects (nine adults, seven children, age range 2-69 years) with celiac sprue were recruited and studied while untreated. Manometric examination was carried out for 6 hr during fasting and 3 hr after a meal. Adult celiac patients displayed a significantly (mean +/- SEM) greater frequency of migrating motor complexes in comparison to controls during fasting (4.44 +/- 1.6 vs 2.45 +/- 0.20, P < 0.01), whereas no differences were found in the pediatric group with respect to this variable. Fasting motor abnormalities, chiefly represented by discrete clustered contractions, giant jejunal contractions, and bursts of nonpropagated contractions, were discovered in a high percentage in both groups of celiac subjects (89% in adults and 44% in children, respectively). Similar abnormalities were observed in the postprandial period, especially in adults. In conclusion, patients with celiac sprue frequently display discrete gastrointestinal motor abnormalities, which though perhaps nonspecific may account for several symptoms complained of by such patients.

Epilepsy with bilateral occipital calcifications: Sturge-Weber variant or a different encephalopathy?

A series of cases of epilepsy with associated bilateral occipital calcifications (EBOC) without signs of phakomatosis and without any disorders known to produce cerebral calcifications have been reported. It is unclear whether EBOC is an incomplete variant of Sturge-Weber disease (SWD) or if it is a different, as yet undefined encephalopathy. We describe four new cases of EBOC that are different clinically by age of onset, type, course, severity of epilepsy, and associated cognitive deficits but that are linked by similar neuroradiologic findings. Similar to cases described in the literature, there is convincing evidence in favor of the hypothesis that these cases belong to an encephalopathy different from SWD and frequently associated with celiac disease.