6-Phosphogluconate dehydrogenase: the mechanism of action investigated by a comparison of the enzyme from different species.

The mechanism of action of 6-phosphogluconate dehydrogenase with the alternative substrate 2-deoxy 6-phosphogluconate was investigated using enzymes from sheep liver, human erythrocytes and Trypanosoma brucei. The three enzymes oxidize 2-deoxy 6-phosphogluconate, but only the sheep liver enzyme releases the intermediate 2-deoxy,3-keto 6-phosphogluconate. Kinetic comparison showed that an increase in the rate of NADP+ reduction at high pH is due to increased release of the intermediate, rather than an increase in the overall reaction rate. 2-Deoxy,3-keto 6-phosphogluconate is decarboxylated by the erythrocyte and trypanosome enzymes but not the liver one in the absence of either NADPH or 6-phosphogluconate, which act as activators. The pH dependence of decarboxylation and the degree of activation suggest that 6-phosphogluconate is the activator which operates under normal assay conditions, while NADPH acts mainly by increasing the binding of the intermediate. The data suggest that the activity of 6PGDH is subjected to a two-way regulation: NADPH, which regulates the pentose phosphate pathway, inhibits the enzyme, while 6-phosphogluconate, levels of which rise when NADPH inhibition is removed, acts as an activator ensuring that 6-phosphogluconate is rapidly removed.

Unusual finding in a nipple discharge of a female dog: dirofilariasis of the breast.

We report a case of dirofilariasis of the breast occurring in a 6-yr-old Bernese female dog living in central Italy presenting with a breast lump, diagnosed on cytological examination of nipple secretion fluid smears. The direct smears of nipple discharge revealed clusters of glandular cells characterized by mild pleomorphic appearance and the presence of some nematodes of about 350 microm in length in the background. The smears also contained several inflammatory cells, including eosinophils. Both the Knott and the antigen tests were negative for Dirofilaria immitis. The morphological features of this round worm is compatible with that of Dirofilaria repens. The case describes an unusual finding of dirofilariasis presenting as a breast lump, simulating an inflammatory breast carcinoma.

Clinical and magnetic resonance features of the classic and akinetic-rigid variants of Huntington's disease.

We studied 32 patients with confirmed Huntington's disease (HD); six (mean age, 31.7 years) had the akinetic-rigid form and 26 (mean age, 46.1 years) had the classic hyperkinetic form. Clinical examination included a count of abnormal involuntary movements, motor self-sufficiency evaluation by the Physical Disability Rating Scale, cognitive function assessment by the Mini-Mental State examination, and a verbal fluency test. Magnetic resonance imaging permitted measurement of bicaudate diameter, a sensitive indicator of caudate atrophy in HD. Patients with the akinetic-rigid form of HD were younger and had earlier disease onset than those with the classic form of HD. All patients with akinetic-rigid HD (group 1) had striatal hyperintensity on T2-weighted magnetic resonance images; seven patients with classic HD (group 2) had a similar abnormality. Groups 1 and 2 were in fact similar in all other respects, except that the number of abnormal involuntary movements was greater in group 2. Groups 1 and 2 together had significantly younger age at onset, lower Mini-Mental State Examination score, more severe motor disability, worse verbal fluency test result, and greater bicaudate diameter than the 19 patients with classic HD without magnetic resonance signal abnormality (group 3) and appear to be a uniform population, distinct from group 3. The abnormalities on magnetic resonance images indicated greater striatal damage in groups 1 and 2, which could be the neuroanatomic substrate of their greater motor and cognitive compromise.

Neuroendocrinologic findings in patients with untreated Huntington's chorea.

Huntington's chorea (HC) was studied in 14 untreated patients, in six patients receiving long-term neuroleptic treatment, and in four patients after drug withdrawal. Our results showed that patients with HC may be divided into three groups, otherwise clinically indistinguishable, on the basis of growth hormone responsiveness to dopaminergic stimuli. The existence of subpopulations of patients with HC must be considered in further studies on these subjects.

Respiratory chain and mitochondrial DNA in muscle and brain in Parkinson's disease patients.

There are several reports of a defect of complex I in the substantia nigra (SN) of Parkinson's disease (PD) patients. To evaluate whether this is specific to dopaminergic neurons or the phenotypically relevant consequence of a widespread failure of the mitochondrial oxidative phosphorylation (OXPHOS) system, we measured respiratory enzyme activities in muscle homogenates from 16 PD patients and eight age-matched controls, and in muscle isolated mitochondria of six PD patients and six age-matched controls. We found no difference between the PD and control groups. In addition, we detected, by polymerase chain reaction, the mitochondrial DNA (mtDNA) "common deletion" (CD) in muscle specimens of 14 of 17 PD patients, but we obtained similar results in age-matched controls. In both groups, the amount of CD-specific deleted (delta) mtDNA ranged from 0.0% to 0.1%. Our data suggest that PD cannot be attributed to a multisystem decline of mitochondrial OXPHOS, and that lesions of muscle mtDNA in PD are likely due to normal aging. However, there was a remarkable accumulation of delta mtDNA in the SN of a PD patient and an age-matched control, suggesting that the SN is exquisitely sensitive to age-dependent damage of the mitochondrial genome.

Gamma-vinyl GABA treatment of Huntington's disease.

In a double-blind, crossover study gamma-vinyl GABA, 2 g/day, and placebo were administered orally for 2 weeks each to six patients with Huntington's disease. Five patients were treated concomitantly with a neuroleptic maintained at constant dose. No consistent beneficial effects on the hyperkinetic movements, abnormal motor function, or ability to carry out normal activities were evident with gamma-vinyl GABA treatment. Treatment was tolerated without clinically significant alterations in the physiologic or biochemical tests used for monitoring. These results suggest that increasing CNS GABAergic function is unlikely to ameliorate Huntington's disease.

Mortality associated with early and late levodopa therapy initiation in Parkinson's disease.

We evaluated the possible influence of early levodopa treatment on the mortality of Parkinson's disease (PD). One hundred forty-five consecutive parkinsonian patients initiated treatment with levodopa between 1970 and 1983. Ninety-eight of those started levodopa therapy 2 or more years after symptom onset, while 47 received levodopa within the 1st 2 years of the disease. At the end of follow-up, in December 1985, 49 patients had died. Mortality was 2.5 times higher among patients who delayed initiation of levodopa therapy 2 or more years than among those who initiated the therapy earlier. Age and disease severity were the most significant predictors of survival after initiation of levodopa treatment. The risk of death was 10% higher every year of age increase and was 2 and 4 times higher, respectively, for patients at Hoehn and Yahr stages II and III than for patients at Hoehn and Yahr stage I. When we controlled for the effect of age and disease severity on mortality, the cumulative death probability was no longer significantly higher among patients who delayed levodopa treatment than among patients treated within 2 years from disease onset. As far as mortality is concerned, the results show that the time of levodopa treatment initiation during PD has no influence and the drug can be introduced as soon as indicated by the severity of the disease progression.

Idiopathic dystonia: neuropharmacological study.

A total of 15 patients affected by idiopathic dystonia (7 with generalized and 8 with focal or segmental dystonia) were subjected to therapy with bromocriptine at low doses, pimozide and trihexyphenidyl. The symptoms were evaluated by giving a progressive score in relation to the intensity of the dystonic symptom to each of the body segments involved by the dystonia. Bromocriptine did not significantly modify the dystonia. Pimozide showed a slight nonsignificant improvement of the dystonic symptoms. Trihexyphenidyl was effective in the generalized dystonias, in agreement with previous reports in the literature. The variation in the pharmacological results could be due to the diversity of the dystonic syndromes, which comprise cases that are different in age at onset, site of dystonic symptoms, and evolution.

Acid-base properties of human gingival crevicular fluid.

The pH of human gingival crevicular fluid (GCF) has been reported by many authors to be very alkaline (pH 7.5 - 8.7). This alkalinity could be explained, at least partially, by the fact that all measurements were performed either at low PCO2 or in the absence of CO2. Therefore, we set up a procedure which allows for measurement of the pH of GCF samples from single inflamed sites at controlled PCO2. At a PCO2 of 4.7 kPa (= 35 mmHg) and at 37 degrees C, the pH was 7.96 +/- 0.10 (SEM, n = 9), a value which differs significantly from the value of 8.38 +/- 0.09 measured in the absence of CO2 in the same samples. The non-bicarbonate buffer value of the sample determined by CO2 titration was 6.0 slykes. It is because this value is low that pH varies so greatly with PCO2. At physiological PCO2, the total buffering power becomes very high above pH 8.0, because of the high bicarbonate concentration.

Pharmacological approaches to Parkinson's disease in the different phases of evolution.

The pharmacological approaches to Parkinson's disease in the different phases of evolution (initial or slight, complete and complicated) are discussed. The modality of confronting the therapeutic approach according to the different evolutive phases makes it possible to personalize the therapy, in an attempt to obtain the optimal clinical effect with minimum side effects. Various drugs available and future perspectives are considered.

Problems arising during chronic treatment with L-dopa for Parkinson's disease: changes in response to treatment.

Some aspects of the problems of long-term L-dopa treatment syndrome are reviewed, with special attention to the changes in response to treatment with dopaminergic agents, specifically end-of-dose deterioration, the on-off phenomenon and hyperkinesia. The various hypotheses for interpreting these are presented, with particular stress on changes in the function of DA-ergic receptors. It is concluded that the on-off phenomenon is probably related to changes in plasma L-dopa levels and to decreased stores of intraneural dopamine.

(-)Deprenyl in Parkinson's disease: a two-year study in the different evolutive stages.

Seventy-nine patients with idiopathic Parkinson's disease in various phases of evolution of the clinical picture were studied. All the patients, already under treatment with L-dopa + PDI, were treated with (-)deprenyl at the dose of 10 mg/day orally in two daily administrations. The mean follow-up was 8.7 months (range, 1-29). Overall, 47.6% of the patients improved, 27.4% showed a marked improvement, 38.1% showed evident modifications, and 27.4% worsened. Sixteen patients were excluded from the study for various reasons. In 53.2% of the cases it was possible to reduce the daily L-dopa dose by a mean of 30%. Overall, (-)deprenyl was effective in the treatment of our parkinsonian patients in the various conditions evaluated, and thus constitutes a new therapeutic strategy for Parkinson's disease.

Lisuride in Parkinson's disease. 4-year follow-up.

Lisuride at a mean daily dose of 3 mg was given to 48 patients with idiopathic Parkinson's disease. Twenty received lisuride alone (Group A) and 36 received lisuride + L-Dopa + peripheral decarboxylase inhibitors (Group B). Dropouts were due primarily to lack of efficacy in Group A patients and to mental side effects in Group B patients. The patients who remained in the study for the full 4 years showed distinct improvement, which was maintained. Group A patients did not have the on-off phenomenon or abnormal involuntary movements.

Response to L-DOPA in multiple system atrophy.

A poor response to L-DOPA in addition to parkinsonian, cerebellar, and autonomic signs is commonly regarded as indicative of clinical multiple system atrophy (MSA). We compared the motor response to a single oral administration of 250 mg L-DOPA/25 mg carbidopa in eight MSA patients and eight Parkinson's disease (PD) patients with the "on-off" phenomenon, evaluating L-DOPA peripheral pharmacokinetics. Motor response was consistently good in all PD patients, but only four MSA patients had a (moderate) response. Pharmacokinetic parameters did not differ between the groups. The varying extent of putaminal damage could be responsible for the differing motor response to L-DOPA in MSA patients.

Research into complementary and alternative medicine across Europe and the United States.

BACKGROUND: There has been an increase in complementary/ alternative medicine (CAM) research with a wide range of perspectives. OBJECTIVE: To capture and analyse the diversity of CAM research across 7 European countries (Germany, United Kingdom, Italy, France, Spain, Netherlands, Belgium) and the US. We were predominantly interested in finding out how CAM research differs between countries. STUDY DESIGN: A systematic review of CAM literature published in 2002 and included in Medline, Embase, International Bibliography of the Social Sciences (IBBS) and PsycLit. OUTCOME CRITERIA: Data were extracted regarding country of origin, type of methodology, type of research question, CAM modality, direction of conclusion, setting and type of journal. RESULTS: In total 652 abstracts of articles were assessed (Germany: 137, UK: 183, Italy: 39, France: 47, Spain: 24, Netherlands: 17, Belgium: 22, US: 183). The vast majority of CAM research was of a medical nature and published in medical journals. The majority of articles were nonsystematic reviews and comments, analytical studies and surveys. The UK carried out more surveys than any of the other countries and also published the largest number of systematic reviews. Germany, the UK and the US covered the widest range of interests across various CAM modalities and investigated the safety of CAM. CONCLUSION: Our data suggest that important national differences exist in terms of the nature of CAM research. This raises important questions regarding the reasons for such differences.

Focal reflex myoclonus in corticobasal degeneration.

Focal reflex myoclonus was observed in a patient clinically diagnosed as affected by corticobasal degeneration. Myoclonus was not preceded by a cortical discharge and contralateral parietal components of the somatosensory evoked potentials were reduced in amplitude. No simple pathophysiological mechanism can account for all cases of focal reflex myoclonus seen in clinical practice.

[Role of surgery in the treatment of simple nodular goiter]. / Il ruolo della chirurgia nel trattamento del gozzo nodulare semplice.

On the basis of the pathophysiological data and their experience, the Authors believe that the medical treatment of non-toxic nodular goiter has many limitations. Furthermore, thyroid nodules may progress uncontrollably till to cancer. Surgery is safe in skilled hands, but in many cases it is necessary to remove the gland extensively. Thus, the best treatment is both medical and surgical, because prevention and cure are associated that way.

An insight into the mechanism of the aerobic oxidation of aldehydes catalyzed by N-heterocyclic carbenes.

N-Heterocyclic carbene catalysis for the aerobic oxidation and esterification of aromatic aldehydes was monitored by ESI-MS (MS/MS) and the key intermediates were intercepted and characterized using the charge-tag strategy.