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Cell encapsulation therapies involve the implantation of cells that secrete a therapeutic factor to provide clinical benefits. The transplanted cells are protected from immunorejection via encapsulation in a semipermeable membrane. This treatment strategy was originally investigated as a method for protecting pancreatic islets from immunorejection, thus allowing them to secrete insulin as a chronic treatment for diabetes. Since then a significant body of work has been conducted in developing cell encapsulation therapies to treat a variety of different diseases. Many of these conditions involve neurodegeneration, such as Alzheimer's and Parkinson's disease, as cell encapsulation therapies have proven to be particularly suitable for delivering therapeutics to the central nervous system. This is mainly because they offer chronic delivery of a therapeutic and can be implanted proximal to the affected tissue, bypassing the blood brain barrier, which is impermeable to many agents. Whilst these therapies are not yet widely available in the clinic, promising results have been obtained in several advanced clinical trials and further developmental work is currently underway. This review specifically examines the development of encapsulated cell therapies as treatments for neurological and sensory diseases and evaluates the challenges that are yet to be overcome before they can be made available for clinical use., (Copyright © 2012 Elsevier B.V. All rights reserved.)

By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks.

We report on a generic procedure to steer (target) a network's dynamics towards a given, desired evolution. The problem is here tackled through a Master Stability Function approach, assessing the stability of the aimed dynamics, and through a selection of nodes to be targeted. We show that the degree of a node is a crucial element in this selection process, and that the targeting mechanism is most effective in heterogeneous scale-free architectures. This makes the proposed approach applicable to the large majority of natural and man-made networked systems.

Neurosecretory vesicles undergo docking and priming before Ca(2+)-dependent fusion with the plasma membrane. Although de novo synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P(2)) is required for exocytosis, its precise contribution is still unclear. Here we show that inhibition of the p110δ isoform of PI3-kinase by IC87114 promotes a transient increase in PtdIns(4,5)P(2), leading to a potentiation of exocytosis in chromaffin cells. We then exploit this pathway to examine the effect of a transient PtdIns(4,5)P(2) increase on neurosecretory vesicles behaviour, outside the context of a secretagogue stimulation. Our results demonstrate that a rise in PtdIns(4,5)P(2) is sufficient to promote the mobilization and recruitment of secretory vesicles to the plasma membrane via Cdc42-mediated actin reorganization. PtdIns(4,5)P(2), therefore, orchestrates the actin-based conveyance of secretory vesicles to the plasma membrane.

Most patients presenting cystinuria require multiple urological procedures during their lifetime. In this kind of patients the availability of minimally invasive procedure represents an advantage of minimizing the cumulative morbidity of several repeated treatments. Herein we report our experience using ureterorenoscopy (URS) for the treatment of recurrent renal cystine stones. From 2003 to 2007, 10 patients (4 males and 6 females) with one or multiple recurrent renal cystine stones underwent URS. Overall, 21 procedures have been performed. Mean maximum diameter of stones was 11.2 mm (range 5-30 mm). Either 8-9.5 F semirigid or 7.9 F flexible ureteroscopes were used. In 6 cases, stones were removed using a basket; in 9 procedures laser lithotripsy with flexible scope was performed; in 6 cases renal calculi were pulled down in the ureter using flexible instrument and then shattered with laser introduced by semirigid instrument. Stone-free status was defined as the absence of any residual fragment. A complete stone clearance was obtained in 15 out of 21 procedures (71%). In 5 cases (24%) significant residual fragments occurred; in the remaining case (5%) URS was ineffective. In 5 out of these unsuccessful procedures, stone clearance was obtained with auxiliary treatments. The last patient has not been treated yet. No major complications occurred as a result of the procedures. URS offers excellent advantages in case of recurrent hard calculi such as cystine stones. Minimally invasive procedures allow satisfactory outcomes, improving patients' quality of life.

Congenital obstructive nephropathy (ON) is one of the most frequent nephropathy observed among newborns and children, and the first cause of end-stage renal diseases treated by dialysis or transplantation. This pathology is characterized by the presence of an obstacle in the urinary tract, e.g., stenosis or abnormal implantation of the urethra in the kidney. In spite of important advances, pathological mechanisms are not yet fully understood. In this contribution, the topology of complex networks created upon vectors of features for control and ON subjects is related with the severity of the pathology. Nodes in these networks represent genetic and metabolic profiles, while connections between them indicate an abnormal relation between their expressions. Resulting topologies allow discriminating ON subjects and detecting which genetic or metabolic elements are responsible for the malfunction.

The activity of networking neurons is largely characterized by the alternation of synchronous and asynchronous spiking sequences. One of the most relevant challenges that scientists are facing today is, then, relating that evidence with the fundamental mechanisms through which the brain computes and processes information, as well as with the arousal (or progress) of a number of neurological illnesses. In other words, the problem is how to associate an organized dynamics of interacting neural assemblies to a computational task. Here we show that computation can be seen as a feature emerging from the collective dynamics of an ensemble of networking neurons, which interact by means of adaptive dynamical connections. Namely, by associating logical states to synchronous neuron's dynamics, we show how the usual Boolean logics can be fully recovered, and a universal Turing machine can be constructed. Furthermore, we show that, besides the static binary gates, a wider class of logical operations can be efficiently constructed as the fundamental computational elements interact within an adaptive network, each operation being represented by a specific motif. Our approach qualitatively differs from the past attempts to encode information and compute with complex systems, where computation was instead the consequence of the application of control loops enforcing a desired state into the specific system's dynamics. Being the result of an emergent process, the computation mechanism here described is not limited to a binary Boolean logic, but it can involve a much larger number of states. As such, our results can enlighten new concepts for the understanding of the real computing processes taking place in the brain.

Background: Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published., Methods and Findings: Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina., Conclusions: Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides.

Sphingosine 1-phosphate (S1P) is a bioactive lipid known to control cell growth that was recently shown to act as a trophic factor for skeletal muscle, reducing the progress of denervation atrophy. The aim of this work was to investigate whether S1P is involved in skeletal muscle fiber recovery (regeneration) after myotoxic injury induced by bupivacaine. The postnatal ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. Immunofluorescence analysis demonstrated that S1P-specific receptors S1P(1) and S1P(3) are expressed by quiescent satellite cells. Soleus muscles undergoing regeneration following injury induced by intramuscular injection of bupivacaine exhibited enhanced expression of S1P(1) receptor, while S1P(3) expression progressively decreased to adult levels. S1P(2) receptor was absent in quiescent cells but was transiently expressed in the early regenerating phases only. Administration of S1P (50 microM) at the moment of myotoxic injury caused a significant increase of the mean cross-sectional area of regenerating fibers in both rat and mouse. In separate experiments designed to test the trophic effects of S1P, neutralization of endogenous circulating S1P by intraperitoneal administration of anti-S1P antibody attenuated fiber growth. Use of selective modulators of S1P receptors indicated that S1P(1) receptor negatively and S1P(3) receptor positively modulate the early phases of regeneration, whereas S1P(2) receptor appears to be less important. The present results show that S1P signaling participates in the regenerative processes of skeletal muscle.

When studying real or virtual systems through complex networks theories, usually time restrictions are neglected, and a static structure is defined to characterize which node is connected to which other. However, this approach is oversimplified, as real networks are indeed dynamically modified by external mechanisms. In order to bridge the gap, in this work we present a scheduled network formalism, which takes into account such dynamical modifications by including generic time restrictions in the structure of an extended adjacency matrix. We present some of its properties and apply this formalism to the specific case of the air transportation network in order to analyze its efficiency. Real data are used at this point. We finally discuss on the applicability of this formalism to other complex systems.

We introduce the concept of decision cost of a spatial graph, which measures the disorder of a given network taking into account not only the connections between nodes but their position in a two-dimensional map. The influence of the network size is evaluated and we show that normalization of the decision cost allows us to compare the degree of disorder of networks of different sizes. Under this framework, we measure the disorder of the connections between airports of two different countries and obtain some conclusions about which of them is more disordered. The introduced concepts (decision cost and disorder of spatial networks) can easily be extended to Euclidean networks of higher dimensions, and also to networks whose nodes have a certain fitness property (i.e., one-dimensional).

The existence of forbidden patterns, i.e., certain missing sequences in a given time series, is a recently proposed instrument of potential application in the study of time series. Forbidden patterns are related to the permutation entropy, which has the basic properties of classic chaos indicators, such as Lyapunov exponent or Kolmogorov entropy, thus allowing to separate deterministic (usually chaotic) from random series; however, it requires fewer values of the series to be calculated, and it is suitable for using with small datasets. In this paper, the appearance of forbidden patterns is studied in different economical indicators such as stock indices (Dow Jones Industrial Average and Nasdaq Composite), NYSE stocks (IBM and Boeing), and others (ten year Bond interest rate), to find evidence of deterministic behavior in their evolutions. Moreover, the rate of appearance of the forbidden patterns is calculated, and some considerations about the underlying dynamics are suggested.

Sphingosine 1-phosphate (S1P) mediates a number of cellular responses, including growth and proliferation. Skeletal muscle possesses the full enzymatic machinery to generate S1P and expresses the transcripts of S1P receptors. The aim of this work was to localize S1P receptors in rat skeletal muscle and to investigate whether S1P exerts a trophic action on muscle fibers. RT-PCR and Western blot analyses demonstrated the expression of S1P(1) and S1P(3) receptors by soleus muscle. Immunofluorescence revealed that S1P(1) and S1P(3) receptors are localized at the cell membrane of muscle fibers and in the T-tubule membranes. The receptors also decorate the nuclear membrane. S1P(1) receptors were also present at the neuromuscular junction. The possible trophic action of S1P was investigated by utilizing the denervation atrophy model. Rat soleus muscle was analyzed 7 and 14 days after motor nerve cut. During denervation, S1P was continuously delivered to the muscle through a mini osmotic pump. S1P and its precursor, sphingosine (Sph), significantly attenuated the progress of denervation-induced muscle atrophy. The trophic effect of Sph was prevented by N,N-dimethylsphingosine, an inhibitor of Sph kinase, the enzyme that converts Sph into S1P. Neutralization of circulating S1P by a specific antibody further demonstrated that S1P was responsible for the trophic effects of S1P during denervation atrophy. Denervation produced the down regulation of S1P(1) and S1P(3) receptors, regardless of the presence of the receptor agonist. In conclusion, the results suggest that S1P acts as a trophic factor of skeletal muscle.

Background: The catalytically active 66-kDa subunit of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) consists of DNA polymerase, connection, and ribonuclease H (RNase H) domains. Almost all known RT inhibitor resistance mutations identified to date map to the polymerase domain of the enzyme. However, the connection and RNase H domains are not routinely analysed in clinical samples and none of the genotyping assays available for patient management sequence the entire RT coding region. The British Columbia Centre for Excellence in HIV/AIDS (the Centre) genotypes clinical isolates up to codon 400 in RT, and our retrospective statistical analyses of the Centre's database have identified an N348I mutation in the RT connection domain in treatment-experienced individuals. The objective of this multidisciplinary study was to establish the in vivo relevance of this mutation and its role in drug resistance., Methods and Findings: The prevalence of N348I in clinical isolates, the time taken for it to emerge under selective drug pressure, and its association with changes in viral load, specific drug treatment, and known drug resistance mutations was analysed from genotypes, viral loads, and treatment histories from the Centre's database. N348I increased in prevalence from below 1% in 368 treatment-naïve individuals to 12.1% in 1,009 treatment-experienced patients (p = 7.7 x 10(-12)). N348I appeared early in therapy and was highly associated with thymidine analogue mutations (TAMs) M41L and T215Y/F (p < 0.001), the lamivudine resistance mutations M184V/I (p < 0.001), and non-nucleoside RTI (NNRTI) resistance mutations K103N and Y181C/I (p < 0.001). The association with TAMs and NNRTI resistance mutations was consistent with the selection of N348I in patients treated with regimens that included both zidovudine and nevirapine (odds ratio 2.62, 95% confidence interval 1.43-4.81). The appearance of N348I was associated with a significant increase in viral load (p < 0.001), which was as large as the viral load increases observed for any of the TAMs. However, this analysis did not account for the simultaneous selection of other RT or protease inhibitor resistance mutations on viral load. To delineate the role of this mutation in RT inhibitor resistance, N348I was introduced into HIV-1 molecular clones containing different genetic backbones. N348I decreased zidovudine susceptibility 2- to 4-fold in the context of wild-type HIV-1 or when combined with TAMs. N348I also decreased susceptibility to nevirapine (7.4-fold) and efavirenz (2.5-fold) and significantly potentiated resistance to these drugs when combined with K103N. Biochemical analyses of recombinant RT containing N348I provide supporting evidence for the role of this mutation in zidovudine and NNRTI resistance and give some insight into the molecular mechanism of resistance., Conclusions: This study provides the first in vivo evidence that treatment with RT inhibitors can select a mutation (i.e., N348I) outside the polymerase domain of the HIV-1 RT that confers dual-class resistance. Its emergence, which can happen early during therapy, may significantly impact on a patient's response to antiretroviral therapies containing zidovudine and nevirapine. This study also provides compelling evidence for investigating the role of other mutations in the connection and RNase H domains in virological failure., Competing Interests: PRH has received honoraria, research and travel grants and served as a speaker from many pharmaceutical companies, and has served as a consultant to HIV drug resistance testing companies including Virco and Monogram Biosciences. SHY, CWS, JF, MZ, DT, VDL, BW, MK, NSC, and GT declare no competing interests.

Postnatal development of skeletal muscle occurs through the progressive transformation of diverse biochemical, metabolic, morphological, and functional characteristics from the embryonic to the adult phenotype. Since muscle regeneration recapitulates postnatal development of muscle fiber, it offers an appropriate experimental model to investigate the existing relationships between diverse muscle functions and the expression of key protein isoforms, particularly at the single-fiber level. This study was carried out in regenerating soleus muscle 14 days after injury. At this intermediate stage, the regenerating muscle exhibited a recovery of mass greater than its force generation capacity. The lower specific tension of regenerating muscle suggested intrinsic defective excitation-contraction coupling and/or contractility processes. The presence of developmental isoforms of both the voltage-gated Ca(2+) channel (alpha(1)C) and of ryanodine receptor 3, paralleled by an abnormal caffeine contracture development, confirms the immature excitation-contraction coupling of the regenerating muscle. The defective Ca(2+) handling could also be confirmed by the lower sarcoplasmic reticulum caffeine sensitivity of regenerating single fibers. Also, regenerating single fibers revealed a lower maximal specific tension, which was associated with the residual presence of embryonic myosin heavy chains. Moreover, the fibers showed a reduced Ca(2+) sensitivity of myofibrillar proteins, particularly those simultaneously expressing the slow and fast isoforms of troponin C. The present results indicate that the expression of developmental proteins determines the incomplete functional recovery of regenerating soleus.

Objectives: To define whether six-core biopsies still have a role in patients presenting with prostate-specific antigen (PSA) levels greater than 10 ng/mL and abnormal digital rectal examination (DRE) findings. Recent studies have suggested that the six-core biopsy is inadequate for the diagnosis of prostate cancer; however, it remains controversial whether an increased number of cores is justified in all patients., Methods: From June 2002 to February 2005, 122 (18.8%) of 650 patients underwent prostate biopsy because of a PSA level greater than 10 ng/mL and abnormal DRE findings. All patients underwent transperineal ultrasound-guided prostate biopsy in a standardized fashion: a six-core biopsy was performed first, followed by six additional cores during the same session, four in the peripheral and two in the transition zone., Results: The detection rate in patients with a PSA level greater than 10 ng/mL and abnormal DRE findings was 72.1% (88 of 122) and 75.4% (92 of 122) using the 6-core and 12-core biopsy, respectively. One case of tumor was missed by the six-core biopsy among patients with a PSA level greater than 15 ng/mL and abnormal DRE findings. No cases of tumor were missed by six-core biopsy in the group with a PSA level greater than 20 ng/mL and abnormal DRE findings., Conclusions: Six-core biopsy provided a similar cancer detection rate compared with 12-core biopsy in patients with PSA levels greater than 10 ng/mL and abnormal DRE findings. An initial approach with 6-core biopsy is reasonable in patients with a PSA level greater than 10 ng/mL and abnormal DRE findings and is advocated in those with PSA greater than 20 ng/mL and abnormal DRE findings.

In experimental autoimmune encephalomyelitis, a classical model for multiple sclerosis, the cytokines provide the necessary signals to activate specific T cells for self-antigens. Gangliosides have multiple immunomodulatory activities, decreasing the lymphoproliferative responses and modulating cytokine production. Here, we tested the effects of gangliosides on the switching of Th1 to Th2 cytokine expression, in spleen cells obtained from Lewis rats during the acute phase of EAE, and after recovery from the disease. For this purpose, total RNA from spleen cells was isolated and submitted to RT-PCR to investigate Th1 (IL-2, TNF-alpha, and IFN-gamma) and Th2/Th3 (IL-10 and TGF-beta) cytokine gene expression. Results demonstrate that the group treated with gangliosides displays mild disease, with low expression of IFN-gamma mRNA and high TGF-beta mRNA expression. We conclude that the gangliosides may modulate Th1 cells by the synthesis of cytokines shifting the profile to the Th2/Th3 phenotype., (Copyright 2004 Elsevier Ltd.)

Insulin-dependent diabetes mellitus is caused by autoimmune destruction of pancreatic beta cells. Non-obese diabetic (NOD) mice spontaneously develop diabetes similar to the human disease. Cytokines produced by islet-infiltrating mononuclear cells may be directly cytotoxic and can be involved in islet destruction coordinated by CD4+ and CD8+ cells. We utilized a semiquantitative RT-PCR assay to analyze in vitro the mRNA expression of TNF-alpha and IFN-gamma cytokine genes in isolated islets (N = 100) and spleen cells (5 x 10(5) cells) from female NOD mice during the development of diabetes and from female CBA-j mice as a related control strain that does not develop diabetes. Cytokine mRNAs were measured at 2, 4, 8, 14 and 28 weeks of age from the onset of insulitis to the development of overt diabetes. An increase in IFN-gamma expression in islets was observed for females aged 28 weeks (149 +/- 29 arbitrary units (AU), P<0.05, Student t-test) with advanced destructive insulitis when compared with CBA-j mice, while TNF-alpha was expressed in both NOD and CBA-j female islets at the same level at all ages studied. In contrast, TNF-alpha in spleen was expressed at higher levels in NOD females at 14 weeks (99 +/- 8 AU, P<0.05) and 28 weeks (144 +/- 17 AU, P<0.05) of age when compared to CBA-j mice. The data suggest that IFN-gamma and TNF-alpha expression in pancreatic islets of female NOD mice is associated with beta cell destruction and overt diabetes.

Although chondroitin sulfate proteoglycans (CSPGs) are major components of the embryonic extracellular matrix, little attention has been paid to specific CSPGs in early heart development, in part because appropriate antibodies were not available. Therefore we prepared specific polyclonal antibodies against chicken aggrecan, versican, neurocan, and phosphacan. Western blotting and immunohistochemical studies revealed the presence of aggrecan and versican in stages 12-21 chicken embryo hearts in distinctive spatial and temporal patterns. Because this is the first demonstration of aggrecan in heart tissue, we further used RT-PCR to confirm that aggrecan is expressed in the heart and in situ hybridization to confirm the pattern of expression determined using antibodies. Versican is found in the myocardium and the myocardial basement membrane. In contrast, aggrecan is specifically colocalized with several groups of migrating cells including endocardial cushion tissue cells, epicardial cells, a mesenchymal cell population in the outflow tract that may be of neural crest origin, and a mesenchymal cell population in the inflow tract. The combined observations indicate that versican and aggrecan are expressed in unique patterns and suggest that they play very different roles in development., (Copyright 1999 Wiley-Liss, Inc.)

Elephantopus scaber has been used in Brazil as a traditional remedy to cause diuresis, antipyresis and to eliminate bladder stones. In the current study, aqueous and hydroalcoholic extracts of whole plants were tested for acute toxicity, analgesic, antipyretic, antiinflammatory, cardiovascular, diuretic and constipating activities. Both extracts (0.3-6 g/kg i.p.) induced writhing, loss of muscle tone, ataxia, prostration and death in mice. No analgesic effects of these extracts were detected using mouse hot-plate and acetic acid-induced writhing tests. Both extracts failed to modify diuresis or carrageenan-induced rat paw edema. In contrast, given intraperitoneally, both reduced brewer's yeast-induced hyperthermia in rats, but when given orally did not affect it. Moreover, the aqueous extract decreased the intestinal transit time in mice while the hydroalcoholic extract increased it. Finally, these extracts, given intravenously, reduced blood pressure and heart rate in rats; these effects could be blocked by atropine but not by co-administration of pyrilamine and cimetidine.

Motor, sensory and thermoregulatory functions were examined in aging rats (12 months) following two schedules of repeated po administration of the carbamate insecticide carbaryl and these effects were assessed in terms of blood cholinesterase activity. Administration of carbaryl (50 mg/kg) by gavage daily for 30 days resulted in a reduction of locomotor activity in the open-field and in an inhibition of cholinesterase activity within 30 min after the last treatment. Twenty-four h later, only the locomotor effect was evident. After 90 days of exposure to carbaryl in drinking water, no significant effects were observed. These findings suggest that repeated administration of carbaryl to aging rats can induce an impairment of motor function and a reduction of cholinesterase activity, while tolerance develops in some other parameters.

In vivo pharmacological studies were carried out with the aqueous and hydroalcoholic extracts of P. punctatum Elliot. Previously we have made a phytochemical screening and a essay of acute toxicity. The extracts exhibited an inhibition of the carrageenan-induced rat paw oedema, at doses of 300 and 600 mg.kg-1 p.o. and the hydroalcoholic extract at a dose range of 100-600 mg.kg-1 p.o. reduced significantly the increase of the vascular permeability induced by histamine. The extracts showed antipyretic activity only by i.p. administration. The gastrointestinal propulsion of a charcoal suspension was affected by both extracts, but significantly only by the aqueous extract. They elicited bradycardia and lowered the arterial blood pressure, but they do not demonstrate analgesic and diuretic activities. The pharmacological effects assayed are discussed in relation to the chemical composition of this plant and also to its popular use.

The effects of acute administration of maneb (30 mg/kg, i.p.), an agricultural fungicide, combined with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP 50 mg/kg, i.p.), a dopaminergic neurotoxin, were examined on mouse locomotor activity and catalepsy test. The pretreatment with maneb significantly exacerbated the effects of MPTP on locomotion and catalepsy in mice. These results suggest that exposure to some pesticides might enhance motor dysfunction.

Fifty-three calisthenics used in a cardiac rehabilitation program were evaluated in a group of patients who, 30-60 days after myocardial infarction, had undergone a multistage symptom-limited bicycle exercise test without S-T segment modifications or arrhythmias. The following measurements were made oxygen uptake (VO2), oxygen uptake/Kg (VO2/Kg), ventilation/m' (VE), heart rate/m' (HR), systolic blood pressure (sBP) and METS. A good correlation was observed during the physical exercises between HR and VO2 (r = 0.59; p less than 0.001) and between HR and VO2/Kg (r = 0.64; p less than 0.001). Such correlation was similar to that observed during bicycle ergometric test. Lower values were obtained for the correlations between sBP and both VO2 and VO2/Kg, but they were still statistically significant (p less than 0.001). Heart rate and sBP were lower during calisthenics than during bicycle exercise from a VO2 level of 600-800 ml up. It is therefore possible to tailor a safe training program based on calisthenics whose level of energy expenditure is known: HRxsBP reached during such physical exercises will be lower than during bicycle ergometric test, VO2 being equal.

High (500 microgram) and low (100 microgram) doses of carrageenin produced different temporal extravasation of plasma protein when injected into the rat paw. High doses caused a continuous extravasation parallel to the oedema increase. With low doses, main exudation occurred during the first 2 h and was minimal when the oedema was maximal (4th hour). Pre-treatment with indomethacin (2 mg/kg/i.p.) was effective in reducing oedema and protein extravasation for both doses of carrageenin. Indomethacin given 2 h after carrageenin had no effect upon the oedema caused by the low doses, but was effective with the high doses of carrageenin. The anti-oedematogenic effect of a non-steroid anti-inflammatory agent, such as indomethacin, was related to its effect upon plasma exudation, i.e. the agent was effective when there was a correlation between increment of oedema and plasma extravasation. The continuously increased plasma extravasation indicated the continuous presence of an active damaging stimulus. Our results explain several apparently contradictory observations reported in the literature.