Influence of aerobic exercise training on the neural correlates of motor learning in Parkinson's disease individuals.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide general health benefits, and to improve motor behaviours in particular, in individuals with Parkinson's disease (PD). However, the influence of AET on their motor learning capacities, as well as the change in neural substrates mediating this effect remains to be explored. OBJECTIVE: In the current study, we employed functional Magnetic Resonance Imaging (fMRI) to assess the effect of a 3-month AET program on the neural correlates of implicit motor sequence learning (MSL). METHODS: 20 healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+ 5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after the AET program, participants' brain was scanned while performing an implicit version of the serial reaction time task. RESULTS: Brain data revealed pre-post MSL-related increases in functional activity in the hippocampus, striatum and cerebellum in PD patients, as well as in the striatum in HC individuals. Importantly, the functional brain changes in PD individuals correlated with changes in aerobic fitness: a positive relationship was found with increased activity in the hippocampus and striatum, while a negative relationship was observed with the cerebellar activity. CONCLUSION: Our results reveal, for the first time, that exercise training produces functional changes in known motor learning related brain structures that are consistent with improved behavioural performance observed in PD patients. As such, AET can be a valuable non-pharmacological intervention to promote, not only physical fitness in early PD, but also better motor learning capacity useful in day-to-day activities through increased plasticity in motor related structures.

Enhancing both motor and cognitive functioning in Parkinson's disease: Aerobic exercise as a rehabilitative intervention.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson's disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. OBJECTIVE: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. METHODS: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after AET, EF tests assessed participants' inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. RESULTS: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. CONCLUSION: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning.

Evaluation of strained alkynes for Cu-free click reaction in live mice.

INTRODUCTION: We report on our evaluation of the strain-promoted cyclooctyne-azide cycloaddition reaction for use in tumor pretargeting, comprising a side-by-side comparison of probes 1-3 bearing three distinct cyclooctyne moieties based respectively on the 1st and 2nd generation difluorinated cyclooctyne and the 1st generation dibenzocyclooctyne. METHODS: The probes were synthesized and labeled with (177)Lu with high yields. The probe stability and reactivity towards azides were evaluated in PBS and mouse serum, and their blood clearance, biodistribution and in vivo reactivity were evaluated in tumor-free mice. RESULTS: In serum the three probes exhibited sufficient stability for a pretargeting application with half-lives of 12-19h. In PBS, probes 2 and 3 were more reactive towards azido-conjugated Rituximab (Rtx-N3) than 1, but in contrast to 1, their reactivity decreased in mouse serum and mouse serum albumin solutions, as a result of covalent and non-covalent interactions with albumin. Biodistribution data confirmed the interactions with serum proteins in circulation: (177)Lu-1 showed a fast elimination from blood (t1/2,ß = 0.31h), while (177)Lu-2 and (177)Lu-3 were retained in blood for longer periods of time (t1/2,ß = 1.08 and 3.58h, respectively). Dual isotope biodistribution experiments assessing the reaction between (125)I-Rtx-N3 and (177)Lu-1-3 in circulation in mice showed a very limited retention of 2 and 3 in blood rich organs, indicating a minimal reactivity, while no such retention was observed for 1. CONCLUSION: The low reactivity of the studied cyclooctynes, and their serum interactions preclude their use at the low in vivo concentrations typical for pretargeting applications.

Comparison between several muscle strength and cardiorespiratory fitness indices with body composition and energy expenditure in obese postmenopausal women.

The purpose of this study was to compare the relationship of several muscle strength and cardiorespiratory fitness indices with body composition and energy expenditure in obese postmenopausal women. This was a cross-sectional study involving 72 obese postmenopausal women (age: 60.0±4.8 years; body mass index: 34.1±3.5 kg/m²). Muscle strength was determined by hand dynamometer and cardiorespiratory fitness was measured by indirect calorimetry. Muscle strength and cardiorespiratory fitness were expressed in absolute (kg and L/min, respectively) and in relative values (kg/body weight (BW) and kg/lean body mass (LBM) for muscle strength and ml/min/kg BW and ml/min kg LBM for cardiorespiratory fitness). Body composition was measured using dual energy x-ray absorptiometry. Anthropometric (waist and thigh circumference), physical activity energy expenditure and daily number of steps (SenseWear armband) as well as blood pressure were also assessed. Correlations of muscle strength and cardiorespiratory fitness indices with body composition and energy expenditure showed several similarities, however, several variations were also observed. Furthermore, our results showed that age and waist circumference were the primary independent predictors for the muscle strength indices, explaining 22-37% of the variance and % body fat and age were the primary predictors for the cardiorespiratory fitness indices, explaining 18-40% of the variance. In conclusion, the present study indicates that the different methods of expressing muscle strength and cardiorespiratory fitness may display several variations and similarities with body composition and energy expenditure associations. Therefore, interpretations of relationships between muscle strength and cardiorespiratory indices with body composition and energy expenditure factors should take in account the method used to express them.

Surgical removal of the pregastric pouch reduces voluntary lactose consumption in golden hamsters.

Unlike other adult mammals, golden hamsters voluntarily consume substantial amounts of the disaccharide sugar lactose. It was hypothesized that the hamster's readiness to consume lactose depends upon its possession of a pregastric pouch in which ingested lactose is broken down into its constituent monosaccharides, thus preventing the aversive gastrointestinal symptoms that monogastric animals experience following lactose ingestion. Adult golden hamsters underwent either surgical removal of the pregastric pouch or sham surgery. Following recovery from surgery, hamsters were given continuous free access for 14 days to tap water, Purina Rodent Chow, a 24% sugar solution (either lactose or sucrose), and a Purina chow-based diet containing 30% added sugar (for each hamster, the same sugar that was provided in solution). Surgical removal of the pregastric pouch caused a 40% reduction in total lactose consumption: this reduction resulted from equivalent decreases in consumption of the lactose solution and the lactose-containing diet. Pouch removal had no effect on total sucrose consumption, and sham surgery had no effect on either lactose or sucrose consumption. These results support the conclusion that the adult hamster's unusually high level of voluntary lactose consumption depends upon its possession of a pregastric pouch, which plays an important role in lactose digestion.

Quantification of diacylglycerols by capillary gas chromatography-negative ion chemical ionization-mass spectrometry.

We describe a method for quantifying diacylglycerols as their 1-pentafluorobenzoyl-2-acyl-3-acetyl-glycerol derivatives by capillary gas chromatography-negative ion chemical ionization-mass spectrometry. The basis of the method resides in the sequential treatment of diacylglycerols with acetic anhydride, pancreatic lipase, and pentafluorobenzoyl chloride. Cultured rat mesenteric artery vascular smooth muscle cells (VSMC) were incubated for 20 min in the presence of vehicle or vasopressin (10(-7) M). The incubations were stopped by aspirating the medium and adding 2 ml of methanol containing 790 pmol of internal standard 1-stearoyl-2-(10,13)-nonadecadienoyl- glycerol. After extraction, diacylglycerols were isolated by thin-layer chromatography, acetylated, and treated with pancreatic lipase. The resulting 2-acyl-3-acetylglycerols were then purified by thin-layer chromatography, transformed into their 1-pentafluorobenzoyl-derivatives, and monitored by capillary gas chromatography-negative ion chemical ionization-mass spectrometry on the selected ion-monitoring mode (m/z 614 and 604 for 2-arachidonoyl and 2-nonadecadienoyl species, respectively). The levels of diacylglycerols bearing an arachidonoyl moiety were 128 +/- 26 pmol/100 nmol lipid phosphorus in resting cells and 333 +/- 28 in stimulated cells (mean +/- SD, n = 3, P < 0.01). The presence of diacylglycerol species bearing an oleoyl or a linoleoyl group at the second position could also be detected in VSMC preparations by this approach. This new method can be applied to quantitate various diacylglycerol species bearing distinct acyl moieties at the second position of the glycerol molecule.

Inhibition of vasopressin-induced formation of diradylglycerols in vascular smooth muscle cells by incorporation of eicosapentaenoic acid in membrane phospholipids.

OBJECTIVE: Eicosapentaenoic acid and linoleic acid exert antihypertensive effects by an unknown mechanism unrelated to prostanoids, a property which is not shared by arachidonic acid. This study investigated the influence of these three acids on the formation of diradylglycerols and phosphatidic acid, key intracellular messengers involved in the mediation of agonist-induced vascular smooth muscle cell contraction. DESIGN: Rat mesenteric artery vascular smooth muscle cells in culture were pre-incubated for 24 h with eicosapentaenoic acid, linoleic acid or arachidonic acid. After thorough washing the cells were then incubated for 20 min in the presence of arginine vasopressin or vehicle, either immediately or following cell labelling with 32P-orthophosphate. METHODS: The fatty acid composition of cell lipids was determined by gas chromatography after transesterification in the presence of boron trifluoride and methanol. Diradylglycerols and 32P-phosphatidic acid were purified from cell lipid extracts by thin-layer chromatography and diradylglycerols were analysed. RESULTS: Incubation of vascular smooth muscle cells with eicosapentaenoic acid, linoleic acid or arachidonic acid resulted in the incorporation of these fatty acids at the sn-2 position of membrane phospholipids, mainly phosphatidylcholine and phosphatidylethanolamine. Eicosapentaenoic acid treatment was associated with a reduction, and linoleic acid treatment with an increase in the relative proportions of arachidonic acid found in cell phospholipids. Arginine vasopressin stimulated the formation of both diradylglycerols and 32P-phosphatidic acid. The arginine vasopressin-induced stimulation of diradylglycerols accumulation was almost completely abolished in eicosapentaenoic acid-treated cells, whereas it was not modified by linoleic acid or by arachidonic acid treatment. The arginine vasopressin-stimulated formation of 32P-phosphatidic acid was significantly inhibited by linoleic acid treatment but was not influenced by eicosapentaenoic acid or arachidonic acid treatment. CONCLUSION: The incorporation of eicosapentaenoic acid or linoleic acid at the sn-2 position of membrane phospholipids leads to an inhibition of arginine vasopressin-induced formation of diradylglycerols or phosphatidic acid, respectively, in rat mesenteric artery vascular smooth muscle cells in culture. These properties may contribute to the antihypertensive effects in these fatty acids in vitro.

Arachidonic acid does not share the antihypertensive properties of linoleic acid and fish oil omega-3 fatty acids in a model of angiotensin II-induced hypertension in the rat.

Linoleic acid and fish oil omega-3 fatty acids, but not arachidonic acid, exerted antihypertensive effects in a model of angiotensin II-induced hypertension in rats. Indomethacin did not influence the systolic arterial pressure of arachidonic acid-treated hypertensive rats whereas compound L-641,953, a prostaglandin H2/thromboxane A2 receptor antagonist, caused a notable but statistically nonsignificant decrease in blood pressure in these animals. Although these results do not exclude entirely the possibility that the lack of antihypertensive effect of arachidonic acid may be due, in part, to the concomitant formation of vasoconstrictor prostanoids, they do not support it. These observations, as well as those of a previous study, indicate that linoleic acid and fish oil omega-3 fatty acids exert antihypertensive effects of their own, independently of the prostanoid system, and that these properties are not shared by arachidonic acid.

[Primary pulmonary choriocarcinoma]. / Choriocarcinome pulmonaire primitif.

The authors report a case of a young woman who had been found to have a chorio-carcinoma in the apex of the left lower lobe, following a major and recurrent haemothorax. A study of her past history and a gynaecological examination had not revealed any evidence of a primary tumour. Following this observation the possibility of a primary pulmonary carcinoma was considered and also the usual aetiological hypothesis, namely the migration of trophoblastic cells during an abortion even followed by a normal pregnancy and a degeneration after several years of these cells blocked in the pulmonary capillaries.

[Reduction using an immunomodulator of the level of respiratory infections in chronic bronchitis]. / Réduction par un immunomodulateur du taux d'infections respiratoires dans la bronchite chronique.

Fifty-six patients with recurrent bronchopulmonary infections associated with chronic bronchitis were randomly allocated to 2 groups, to assess whether treatment with an immunomodulator, Diribiotin CK, could enhance resistance to infection. The double-blind, placebo-controlled prospective trial over a 9 month period showed that this immunomodulator was well tolerated and significantly reduced the rate of respiratory tract infection. The drug also significantly reduced the prescribing of antibiotic medication and the rate of absenteism from work. These effects have been demonstrated in a rigorously designed clinical study. This is the first time that a clear clinical activity has been attributed to an inducer of soluble mediators of immunity.

[Respiratory complications of anticancer chemotherapy]. / Complications respiratoires de la chimiothérapie anticancéreuse.

Pulmonary toxicity associated with chemotherapy is still rare, but its incidence may increase with intensive and iterative regimens. Following a review of the four main drugs responsible for lung toxicity (bleomycin, methotrexate, busulfan and BCNU), the authors underline the risk of combined chemotherapy and radiotherapy. To recognize, at an early stage, the signs suggesting lung toxicity is essential to reduce its extent and, above all, to exclude other pathologies which often have the same clinical and radiological features. Only histological studies provide evidence of toxicity. Treatment is frequently disappointing; the only hope of regression lies in withdrawal of the responsible drug and corticosteroid therapy.

Urinary levels of 2,3-dinor-6-oxo-PGF1 alpha: a reliable index of the production of PGI2 in the spontaneously hypertensive rat.

The urinary levels of 2,3-dinor-6-oxo-PGF1 alpha (PGI2-M), a major metabolite of PGI2, are determined by the balance between the amount of PGI2 synthesized and the extent of its further metabolic oxidation. The purpose of the present study was to determine if the urinary excretion of PGI2-M can be used as a reliable index of the in vivo production of PGI2 in both normal Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). This involved the exclusion of differences in metabolism between these two strains of rats. In order to do so, we monitored the urinary excretion of PGI2-M during paired intravenous infusions of 6-oxo-PGF1 alpha (the stable product of the spontaneous hydrolysis of PGI2) in conscious, unrestrained SHR and WKY rats aged 12-15 weeks, in doses ranging from 250 to 700 ng. In one experiment, PGI2 was infused instead of 6-oxo-PGF1 alpha. The results of these experiments indicate that SHR and WKY rats are equal with regard to the transformation of 6-oxo-PGF1 alpha and PGI2 into PGI2-M. For both groups, there is a good correlation between the amount of 6-oxo-PGF1 alpha infused and the amount of PGI2-M excreted in urine. These observations confirm the validity of using the urinary levels of 2,3-dinor-6-oxo-PGF1 alpha as an index of PGI2 production in both WKY and SHR. In addition, they support the conclusions drawn from our previous studies, namely that SHR do not produce more PGI2 than WKY rats in vivo, contrary to the situation prevailing in vitro.

Graft-versus-host disease in murine bone marrow transplantation. II. Modulation of acute and chronic GVHD in mice receiving bone marrow allografts pretreated with immunosuppressive factor derived from a human T cell line.

BALB/c bone marrow treated with monoclonal anti-Thy 1.2 antibody and complement is unable to produce prolonged hemopoietic repopulation and survival when transplanted to lethally-irradiated allogeneic CBA recipient mice. Preincubation of the antibody treated bone marrow cells with an immunosuppressive factor (SAF) derived from a 6-thioguanine resistant cell line, itself derived from the human T cell line CEM, in contrast, allowed those bone marrow cells to produce a state of chimerism and long term survival. Parameters designed to gauge the degree of graft-versus-host reactivity (GVHR) in these animals suggested that acute GVHR was abolished with this procedure. Moreover, defining chronic GVHD as associated with abnormally high spontaneous proliferation of splenic cells, elevated anti-host mixed lymphocyte reactivity, or elevated serum immunoglobulin levels (in all cases when compared with the syngeneically repopulated BALB/c----BALB/c), our data suggest that preincubation with SAF modified chronic GVHD also.

Graft-versus-host disease in murine bone marrow transplantation. I. Modification of GVHD by preimmunization of recipients with spleen cells of primary recipients undergoing GVHD.

Lethally irradiated (1000 rad) CBA/J mice were transplanted with anti-Thy 1 treated BALB/c bone marrow. Under these conditions, we uniformly observed the development of pathology suggestive of acute graft-vs.-host disease (GVHD), i.e. weight loss, diarrhoea, hypogammaglobulinemia and thymic hypoplasia. If, 2 wk before irradiation, the recipients were preimmunized with spleen cells taken from mice undergoing acute GVHD, these symptoms were avoided. Instead, such animals seemed to show long term survival either with or without signs of chronic GVHD (hypergammaglobulinemia, splenomegaly, lymphoid hyperplasia). The ability to show long term survival with bone marrow allografts was dependent upon successful immunization of the recipient mice. Long term survivors contain a splenic population not bearing detectable host MHC antigens, which can elicit a memory anti-host cytotoxic response from a population of quiescent donor lymphocytes previously immunized in vitro against host MHC antigens.

Defective synthesis of vasodilator prostaglandins in the spontaneously hypertensive rat.

Results of in vitro studies performed in different laboratories have led to the hypothesis that in spontaneously hypertensive rats (SHR), the biosynthesis of the vasodilator prostaglandins (PG) I2 and E2 increases secondarily to the rise in the arterial pressure, as a protective mechanism for reducing the severity of hypertension. In this study, this hypothesis was tested in vivo in SHR and control Wistar-Kyoto (WKY) rats under normal and high sodium diets. The 24-hour urinary excretion of 2,3-dinor-6-oxo-PGF1 alpha, an endogenous metabolite of PGI2, was used as an index of the total production of PGI2 in the rats, whereas the urinary levels of PGE2 were used as an index of the renal production of this prostaglandin. Urinary levels of PGE2, obtained at 10 and 12 weeks of age, were always lower in SHR than in WKY rats and were not influenced by dietary sodium. In WKY and SHR on normal diets, the urinary levels of 2,3-dinor-6-oxo-PGF1 alpha did not differ significantly. However, the chronic administration of a high sodium diet (5.9% NaCl) was accompanied by a significant and sustained rise in the urinary excretion of 2,3-dinor-6-oxo-PGF1 alpha in the order of 30% to 50% in WKY but not in SHR, a finding similar to that in Dahl rats. These results point to the existence of an impaired capacity in SHR to synthesize vasodilator prostaglandins in vivo, contrary to the situation prevailing in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)