Effects of a unilateral stereotaxic injection of Tinuvin 123 into the substantia nigra on the nigrostriatal dopaminergic pathway in the rat

Tinuvin 123, a compound used in the manufacture of plastics, has recently been suggested to possibly cause Parkinson's disease (PD). Herein, we revisited this issue by assessing the effect of Tinuvin 123 on dopaminergic neurons of the substantia nigra following its stereotaxic injection in the rat. Twenty-one days post unilateral stereotaxic injection of Tinuvin 123, systemic injection of both apomorphine and amphetamine caused rotations toward the side of the lesion in these rats. Tinuvin 123 produced a small to moderate dose-dependent reduction in striatal levels of dopamine and metabolites on the side of the lesion. This compound also produced dramatic cell loss in the substantia nigra on the side of the lesion. However, the loss of cells lacked the phenotypic specificity for tyrosine hydroxylase (TH)-positive neurons that is expected with a dopaminergic neurotoxin. Indeed, aside from a robust glial reaction, both TH-positive and glutamic acid dehydrogenase (GAD)-positive neurons were destroyed, and near the site of the injection, there was complete tissue destruction. This study indicates that, using this mode of injection, Tinuvin 123 exerts a dramatic tissue toxicity without any evidence of specificity for dopaminergic neurons. Thus, our data argues against a role for Tinuvin 123 as an environmental toxin causing a clinical condition characterized by the selective loss of dopaminergic neurons as seen in PD.     

Estrogen reduces acute striatal dopamine responses in vivo to the neurotoxin MPP+ in female, but not male rats

The effects of in vivo estrogen treatment upon MPP⁺-induced dopamine (DA) release were determined using in vivo microdialysis in female and male rats. Ovariectomized female rats were implanted or not with an estrogen pellet (0.1 mg, 17β estradiol) and subjected to microdialysis 6 days later. After baseline DA release was determined, 5 mM MPP⁺ was infused through the microdialysis probe for one 20-min interval. Perfusion resumed with normal medium for the duration of the experiment. A significant attenuation of MPP⁺-induced DA release was obtained in estrogen-treated females. One week later, striatal DA and dihydroxyphenylacetic acid (DOPAC) concentrations were determined for the lesioned and non-lesioned striata of each animal. MPP⁺ infusion significantly decreased striatal DA concentrations, however, there was no effect of estrogen treatment on striatal DA depletion. This experiment was repeated using orchidectomized male rats treated with 0, 0.1, or 5 mg estradiol. In contrast to the females, no differences in MPP⁺-induced DA release were seen among these males, and there was no significant effect of the varying estrogen treatments on striatal DA or DOPAC concentrations. These results demonstrate that in vivo estrogen treatment attenuates MPP⁺-induced striatal DA release in gonadectomized female, but not male, rats.     

Preferential resistance of dopaminergic neurons to glutathione depletion in a reconstituted nigrostriatal system

Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD), and could initiate dopaminergic neuronal degeneration. Nevertheless, we have previously demonstrated that mesencephalic dopaminergic neurons in primary monolayer cultures are more resistant to the toxicity of glutathione depletion than nondopaminergic neurons. To extend this finding to a system that more closely resembles the in vivo situation, we characterized the effects of glutathione depletion on reaggregate cultures derived from ventral mesencephalic and their striatal target neurons, as well as supporting elements including glia. Dopaminergic neurons were found to be more resistant to the toxicity of buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, than other nigrostriatal neurons, while striatal target cells exhibited an intermediate susceptibility when examined after 48 h. Glutathione depletion, however, decreased the intracellular content of catecholamines after 48 h and eventually led to the loss of dopaminergic neurons after 7 days. Our data indicate that the intrinsic resistance of dopaminergic neurons to the toxicity of glutathione depletion occurs in a variety of experimental paradigms, and suggest that global glutathione depletion alone is unlikely to account for the selective loss of dopaminergic neurons in PD. Rather, it is more likely that either the selective loss of glutathione from dopaminergic neurons, or the combination of glutathione loss with other insults contributes to the preferential death of dopaminergic neurons in PD.     

Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss

After administration of methamphetamine (METH) (2x2 mg/kg, 6 h apart) to vervet monkeys, long term but reversible dopaminergic deficits were observed in both in vivo and post-mortem studies. Longitudinal studies using positron emission tomography (PET) with the dopamine transporter (DAT)-binding ligand, [11C]WIN 35,428 (WIN), were used to show decreases in striatal WIN binding of 80% at 1 week and only 10% at 1.5 years. A post-mortem characterization of other METH subjects at 1 month showed extensive decreases in immunoreactivity (IR) profiles of tyrosine hydroxylase (TH), DAT and vesicular monoamine transporter-2 (VMAT) in the striatum, medial forebrain bundle and the ventral midbrain dopamine (VMD) cell region. These IR deficits were not associated with a loss of VMD cell number when assessed at 1.5 years by stereological methods. Further, at 1.5 years, IR profiles of METH subjects throughout the nigrostriatal dopamine system appeared similar to controls although some regional deficits persisted. Collectively, the magnitude and extent of the dopaminergic deficits, and the subsequent recovery were not suggestive of extensive axonal degeneration followed by regeneration. Alternatively, this apparent reversibility of the METH-induced neuroadaptations may be related primarily to long-term decreases in expression of VMD-related proteins that recover over time.     

Le deuil, expérience de fraternité et d’altérité. Le groupe d’entraide, expérience d’appartenance

Résumé: La société d’aujourd’hui provoque une marginalisation des personnes en deuil; l’individu est abandonné à lui-même; il y a risque de perte du lien social et de l’estime de soi. Le groupe d’entraide offre la possibilité de recréer du lien social en faisant vivre une expérience d’appartenance, qui s’ancre avant tout sur la force du récit et du témoignage et repose sur un cadre rigoureux. L’Lécoute et le partage au sein du groupe contribuent à élargir les ressources de chacun, à donner ou à redonner de la confiance dans ses capacités de répondre à l’épreuve, engendrant ainsi une bonne image de soi et son rôle. Parce que le processus de deuil n’est pas linéaire, cela nécessite de respecter le temps, le rythme propre à chacun. L’auteur s’appuie sur son expérience de la perte d’un enfant et de l’animation de groupes d’entraide pour parents en deuil «Apprivoiser l’absence».Dossier: «Cliniques du cancer»Dominique Davous Animatrice de groupes d’entraide pour parents en deuil Apprivoiser l’absence, au sein de l’association Choisir l’Espoir Île-de-France; auteur-coordonnateur avec Annick Ernoult d’Animer un groupe d’entraide pour personnes en deuil. L’Harmattan, collection Au-delà du témoignage, Paris, 2001; auteur d’À l’aube du huitième jour... Capucine. L’Harmattan, collection Écritures, Paris, 1997; coordonnatrice d’un groupe de réflexion et de recherche Espace éthique AP-HP: Parents et soignants face à l’éthique en pédiatrie www.espace-ethique.org     

Médecin traitant et médecin correspondant: mécanisme et missions

Résumé: La loi du 13 août 2004 relative à l’assurance maladie a instauré un système de coordination des soins reposant sur une centralisation de la prise en charge par un médecin traitant choisi par le patient.Dans ce système en vigueur depuis le 1^er juillet 2005, le médecin traitant assure la coordination des soins et les soins de premier recours. Les médecins intervenant en concertation avec le médecin traitant, les médecins correspondants, assurent quant à eux le second recours au système de soins, et notamment les soins les plus spécialisés.Les patients qui ne désignent pas un médecin traitant seront financièrement pénalisés.D’un commun accord avec son patient, tout cancérologue peut exercer la fonction de médecin traitant.     

Whole-exome sequencing identifies novel mutations in genes responsible for retinitis pigmentosa in 2 nonconsanguineous Chinese families

AIM: To detect the pathogenetic mutations responsible for nonsyndromic autosomal recessive retinitis pigmentosa (RP) in 2 nonconsanguineous Chinese families. METHODS: The clinical data, including detailed medical history, best corrected visual acuity (BCVA), slit-lamp biomicroscope examination, fundus photography, optical coherence tomography, static perimetry, and full field electroretinogram, were collected from the members of 2 nonconsanguineous Chinese families preliminarily diagnosed with RP. Genomic DNA was extracted from the probands and other available family members; whole-exome sequencing was conducted with the DNA samples provided by the probands, and all mutations detected by whole-exome sequencing were verified using Sanger sequencing in the probands and the other available family members. The verified novel mutations were further sequenced in 192 ethnicity matched healthy controls. RESULTS: The patients from the 2 families exhibited the typical symptoms of RP, including night blindness and progressive constriction of the visual field, and the fundus examinations showed attenuated retinal arterioles, peripheral bone spicule pigment deposits, and waxy optic discs. Whole-exome sequencing revealed a novel nonsense mutation in FAM161A (c.943A>T, p.Lys315*) and compound heterozygous mutations in RP1L1 (c.56C>A, p.Pro19His; c.5470C>T, p.Gln1824*). The nonsense c.5470C>T, p.Gln1824* mutation was novel. All mutations were verified by Sanger sequencing. The mutation p.Lys315* in FAM161A co-segregated with the phenotype, and all the nonsense mutations were absent from the ethnicity matched healthy controls and all available databases. CONCLUSION: We identify 2 novel mutations in genes responsible for autosomal recessive RP, and the mutation in FAM161A is reported for the first time in a Chinese population. Our result not only enriches the knowledge of the mutation frequency and spectrum in the genes responsible for nonsyndromic RP but also provides a new target for future gene therapy.     

论治脾法在小儿新型冠状病毒肺炎中的应用

基于“脾乃后天之本”理论及小儿“脾常不足”的生理特点,且新型冠状病毒肺炎(corona virus disease 2019,COVID-19,简称“新冠肺炎”)患儿具有“易于感邪,易于康复”“肺先受邪,肺脾同病”的病理特点,认为治脾法在小儿新冠肺炎的临床防治中起着关键作用,补气益肺(培土生金)、补中固本、健脾祛湿、健...     

Advances in Bovine Coronavirus Epidemiology

Bovine coronavirus (BCoV) is a causative agent of enteric and respiratory disease in cattle. BCoV has also been reported to cause a variety of animal diseases and is closely related to human coronaviruses, which has attracted extensive attention from both cattle farmers and researchers. However, there are few comprehensive epidemiological reviews, and key information regarding the effect of S-gene differences on tissue tendency and potential cross-species transmission remain unclear. In this review, we summarize BCoV epidemiology, including the transmission, infection-associated factors, co-infection, pathogenicity, genetic evolution, and potential cross-species transmission. Furthermore, the potential two-receptor binding motif system for BCoV entry and the association between BCoV and SARS-CoV-2 are also discussed in this review. Our aim is to provide valuable information for the prevention and treatment of BCoV infection throughout the world.