Parkinson's disease: Evolution of the scientific literature from 1983 to 2017 by countries and journals.

This study charts the evolution of the scientific literature on Parkinson's disease (PD) from 1983 to 2017 to inform communities of scientists, physicians, patients, caregivers and politicians concerned with PD. Articles published in journals indexed in the Science Citation Index-Expanded database of the Web of Science were retrieved and analyzed in seven five-year periods: 1983-1987, 1988-1992, 1993-1997, 1998-2002, 2003-2007, 2008-2012 and 2013-2017. Over 35 years the number of research papers on PD increased 33-fold: 885 papers in 1983-1987 to 29,972 in 2013-2017. At the same time the number of countries contributing to PD research increased from 37 to 131. The USA was the most prolific country throughout, followed by several European (UK, Germany, Italy and France) and English-speaking (Canada and Australia) countries. By 2003, several Asian countries (China, South Korea, India and Turkey) emerged with rapid increases in publications related to PD. By 2013-2017, China surpassed all but the USA to rank 2nd globally in productivity. Despite an increase from 4 to 22 African countries publishing PD research from 1983 to 2017, most were either unproductive or contributed ≤5 papers in each five-year period. There has also been a 12-fold increase in the number of journals (232-2824) containing papers on PD. In 2013-2017 three PD-focused journals (Parkinsonism & Related Disorders, Movement Disorders and Journal of Parkinson's Disease) contained 6.8% of all PD papers while a large majority (82.5%) of journals published ≤ 10 papers. This quantitative study complements the numerous extant qualitative reviews to provide a global perspective on PD research.

Evolution of the scientific literature on drug delivery: A 1974-2015 bibliometric study.

This study charts the growth of the drug delivery literature published during 1974-2015 from journals indexed in the Science Citation Index Expanded database. The growth of publications on drug delivery paralleled the total scientific publications for three decades (1974-2003); however, from 2004 to 2015 it exploded fourfold, while the total increased only 1.75 fold. Industrialized countries (USA, UK, Germany, Japan, Italy, France and Canada) were the most prolific during the first decades, but in 2014-2015 China, India and South Korea ranked 1st, 3rd and 4th respectively among the productive countries. The number of participating countries increased fivefold (from 19 to 96). During the last 15years, the journals targeted by drug delivery research increased nearly 2.4 fold (416 to 1001) and three journals (Journal of Controlled Release, Advanced Drug Delivery Reviews, and International Journal of Pharmaceutics) published nearly one-fifth of the drug delivery research in 2014-2015.

Utilisation of the c-fos immunohistochemical method: a 2004 quantitative study.

The aim of this study was to provide a quantitative view of the utilisation of the c-fos immunohistochemical method. Articles including the term "c-fos" in their title, abstract or keywords and published in 2004 were retrieved from the Current Content/Life Sciences or Current Content/Clinical Medicine collection of the SCI database. The 933 article-type documents retained were distributed in almost all the sub-disciplines of the Life Sciences and Clinical Medicine, but were principally published in the field of neuroscience. They were authored by researchers from 44 countries - the most prolific were the USA (435 articles), Japan (135) and the UK (55). The 933 articles were published in 283 different journals; all but one of the top-20 most prolific journals are in the Life Sciences discipline, and their Impact Factors ranged from 2.0 to 7.9. A comparison of the USA and the European Union scientific profiles is also made.

Use of the jaw opening reflex for assessing the effects of local anaesthetics in freely moving rats.

INTRODUCTION: In order to characterize a nonbehavioral model for assessing local anaesthetic (LA) activity, the effects of different LA agents (articaine, bupivacaine, procaine, and tetracaine) were measured in the conscious rat using the jaw-opening reflex (JOR). METHODS: One hundred sixty rats were chronically implanted with stimulating electrodes in the dental pulp of the low incisor. While animals were conscious and unrestrained, the JOR threshold was measured electrophysiologically via electrodes wrapped around the digastric muscle. Each LA was administered in the infratemporal area. The increase of the JOR threshold was assessed during a 3-h period following injection. RESULTS: Statistical analysis of the data showed a dose-dependent response to the four drugs tested. When the highest dose of each drug (articaine and procaine: 24 mg kg(-1), bupivacaine: 6 mg kg(-1), tetracaine: 3 mg kg(-1)) was administered (i) an immediate effect was observed for tetracaine and bupivacaine, whereas a 5-min delay was needed for articaine and procaine to act on the JOR threshold and (ii) an increase (>60%) of the JOR threshold was observed. The effects lasted 90 min for articaine, 45 min for procaine and bupivacaine, and 15 min for tetracaine before a return to baseline values. DISCUSSION: The rat JOR response combined with infratemporal injection of test drugs can be used for the pharmacological evaluation of LAs.

The LPS-induced neutrophil recruitment into rat air pouches is mediated by TNFalpha: likely macrophage origin.

The role of resident cells during the lipopolysaccharide (LPS)-induced neutrophil recruitment into rat air pouches was investigated. In this model, LPS (Escherichia coli, O55: B5 strain; 2-2000 ng) induced a dose- and time-dependent neutrophil recruitment accompanied by the generation of a tumour necrosis factor-alpha (TNFalpha)-like activity. Dexamethasone (0.05-5 mug) and cycloheximide (6 ng), injected 2 h before LPS into the pouches, inhibited the neutrophil recruitment and the generation of the TNFalpha-like activity, while the H1-receptor antagonist mepyramine (1 and 4 mg/kg, i.p., 0.5 h before LPS) and the PAF-receptor antagonist WEB 2170 (0.05 and 1 mg/kg, i.p., 0.5 h before LPS) had no effect. Purified alveolar macrophages (AM) were used to replenish the pouches of cycloheximide-treated recipient rats. AM provided by PBS-treated animals led to the recovery of the LPS-induced neutrophil recruitment and of the TNFalpha-like formation contrasting with those from cycloheximide-treated animals (1 mg/kg, i.p.). When delivered in situ, liposome-encapsulated clodronate, a macrophage depletor, significantly impaired both the LPSinduced neutrophil recruitment and the TNFalpha-like activity. An anti-murine TNFalpha polyclonal antibody (0.5 h before LPS) was also effective. These results emphasize the pivotal role of macrophages for LPS-induced neutrophil recruitment via the formation of TNFalpha.

Albumin exchange and inflammatory cell recruitment in lungs of antigen-challenged guinea pigs: role of histamine.

Microvascular albumin exchange and sequestration of inflammatory cells into the lungs of anesthetized guinea pigs immunized to ovalbumin were evaluated using radioactive tracers. Increased exchange of radiolabeled (*) albumin from airways to blood was noted in immunized and boosted animals under basal conditions. After the intratracheal injection of 300 micrograms of ovalbumin, an additional increase in exchange through epithelium occurred, since the rate of appearance of *albumin in blood was enhanced compared with control (140 +/- 30 vs. 54 +/- 20% in 1 h). The augmentation of lung content in extravascular *albumin compared with control (16.2 +/- 4.0 vs. 5.9 +/- 1.6%) indicates that transendothelial exchange was also facilitated. Concomitment with the sequestration of *platelets into the lungs of antigen-challenged sensitized animals (59.2 +/- 20% in 1 h), leukocytes (> 60% polymorphonuclear neutrophils) did not marginate. Histamine released during antigenic shock might promote leukocyte demargination from the vascular bed through its vasomotor effect and/or by inhibiting leukocyte activation and consequently may counteract the effects of other inflammatory mediators acting to sequester neutrophils. In confirmation, perfusion of histamine to the immunized animals induced demargination of lung leukocytes. Histamine antagonists prevented the increased exchange of *albumin through the epithelial and endothelial barriers and uncovered *leukocyte sequestration (100.7 +/- 28.9% in 1 h) in the lungs of antigen-challenged animals. Histamine antagonists may favor antigen-induced leukocyte sequestration in the lungs by preventing the effects of endogenous histamine on capillary recruitment and blood flow.

Pharmacological differentiation by pertussis toxin of the in vivo acute responses to fMLP and PAF in guinea-pig lungs.

1. The effects of pertussis toxin on the N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and platelet-activating factor (PAF)-induced variations in pulmonary capillary albumin exchanges, blood volume, leucocyte or platelet sequestration were studied in the guinea-pig, by use of radioactive tracers. The effects of pertussis toxin on pulmonary insufflation pressure were studied in parallel. 2. The i.v. administration of fMLP and PAF to the guinea-pig was followed by bronchoconstriction, increased lung capillary albumin exchanges (vasopermeability) sequestration of leucocytes, leucopenia and reduction of blood volume (vasoconstriction). PAF also induced platelet sequestration in lungs and thrombocytopenia. 3. Pertussis toxin (10 micrograms kg-1, i.v., 72 h before the experiment) prevented all the studied fMLP-induced effects, but failed to modify PAF-induced bronchoconstriction, lung vasoconstriction, platelet sequestration, thrombocytopenia and the increased capillary vasopermeability. In the same conditions the lung leucocyte sequestration was not significantly affected when leucopenia was partially reduced. 4. It is suggested that the effects of fMLP, but not those of PAF, involve a Gi-like protein.

Thromboxane A2 accounts for bronchoconstriction but not for platelet sequestration and microvascular albumin exchanges induced by fMLP in the guinea pig lung.

When injected i.v. to guinea pigs, the granulocyte secretagog N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) induces bronchoconstriction (BC), lung platelet sequestration and increased transendothelial albumin exchanges in lungs. We evaluated BC and the variations of the lung contents in radiolabeled platelets, erythrocytes and extravascular albumin, as measurements of platelet lung entrapment, reduction of lung blood volume and increase of transendothelial albumin exchanges, respectively. Trimetoquinol, a thromboxane A2 (TXA2)-endoperoxide receptor antagonist, inhibited BC and platelet entrapment by lungs induced by fMLP, but protection was nonspecific because it also suppressed BC by histamine. The specific TXA2 synthetase inhibitor/endoperoxide receptor antagonist ridogrel suppressed BC and reduced lung platelet entrapment, but failed to prevent the increase of extravascular albumin and the decrease of erythrocyte lung contents due to fMLP. Consequently, the fMLP-induced increase of vascular albumin exchanges and reduction of lung blood volume are TXA2-independent. Aspirin prevented BC, but failed to suppress lung platelet entrapment by fMLP, indicating that in vivo platelet activation is not TXA2-dependent, even though the levels of circulating TXB2, the stable metabolite of TXA2, were increased after fMLP concomitantly with that of 6-keto-prostaglandin (PG)F1 alpha, the stable metabolite of PGI2. The ridogrel-treated animals showed reduced blood level of TXB2 and increased levels of 6-keto-PGF1 alpha after fMLP challenge. Blocking the cyclooxygenase pathway with aspirin prevented ridogrel-induced protection against lung platelet sequestration after fMLP, supporting the concept that rechanneling of arachidonate metabolism toward protective prostaglandins accounts for protection by ridogrel.

[Effect of chlorhexidine on bacterial fibrinolytic and collagenolytic activity]. / Effet de la chlorhexidine sur des activités fibronectinolytiques et collagenolytiques bactériennes.

Destructive periodontal diseases are characterized by tissue breakdown partly mediated by various enzymes originating from bacteria and/or tissue. Collagen and fibronectin are two of the main substrates available for enzyme activity. Since chlorhexidine is largely used during and after periodontal therapy, we have investigated the effects of chlorhexidine upon some bacterial proteases. Our data indicate that chlorhexidine inhibits, on a dose-dependent manner, both fibronectin and collagen hydrolysis mediated by either bacteroides (porphyromonas) gingivalis or bacteroides intermedius. Thus, it might be hypothesized that a side from its bactericidal activity, chlorhexidine helps to prevent periodontal tissue destruction directly by enzyme inhibition.