Exercise protects synaptic density in a rat model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is characterized by Lewy body and neurite pathology associated with dopamine terminal dysfunction. Clinically, it is associated with motor slowing, rigidity, and tremor. Postural instability and pain are also features. Physical exercise benefits PD patients - possibly by promoting neuroplasticity including synaptic regeneration. OBJECTIVES: In a parkinsonian rat model, we test the hypotheses that exercise: (a) increases synaptic density and reduces neuroinflammation and (b) lowers the nociceptive threshold by increasing µ-opioid receptor expression. METHODS: Brain autoradiography was performed on rats unilaterally injected with either 6-hydroxydopamine (6-OHDA) or saline and subjected to treadmill exercise over 5 weeks. [3H]UCB-J was used to measure synaptic vesicle glycoprotein 2A (SV2A) density. Dopamine D2/3 receptor and µ-opioid receptor availability were assessed with [3H]Raclopride and [3H]DAMGO, respectively, while neuroinflammation was detected with the 18kDA translocator protein (TSPO) marker [3H]PK11195. The nociceptive threshold was determined prior to and throughout the exercise protocol. RESULTS: We confirmed a dopaminegic deficit with increased striatal [3H]Raclopride D2/3 receptor availability and reduced nigral tyrosine hydroxylase immunoreactivity in the ipsilateral hemisphere of all 6-OHDA-injected rats. Sedentary rats lesioned with 6-OHDA showed significant reduction of ipsilateral striatal and substantia nigra [3H]UCB-J binding while [3H]PK11195 showed increased ipsilateral striatal neuroinflammation. Lesioned rats who exercised had higher levels of ipsilateral striatal [3H]UCB-J binding and lower levels of neuroinflammation compared to sedentary lesioned rats. Striatal 6-OHDA injections reduced thalamic µ-opioid receptor availability but subsequent exercise restored binding. Exercise also raised thalamic and hippocampal SV2A synaptic density in 6-OHDA lesioned rats, accompanied by a rise in nociceptive threshold. CONCLUSION: These data suggest that treadmill exercise protects nigral and striatal synaptic integrity in a rat lesion model of PD - possibly by promoting compensatory mechanisms. Exercise was also associated with reduced neuroinflammation post lesioning and altered opioid transmission resulting in an increased nociceptive threshold.

Decreased expression of the mitochondrial matrix proteases Lon and ClpP in cells from a patient with hereditary spastic paraplegia (SPG13).

The mitochondrial chaperonin heat shock protein 60 (Hsp60) assists the folding of a subset of proteins localized in mitochondria and is an essential component of the mitochondrial protein quality control system. Mutations in the HSPD1 gene that encodes Hsp60 have been identified in patients with an autosomal dominant form of hereditary spastic paraplegia (SPG13), a late-onset neurodegenerative disorder characterized by a progressive paraparesis of the lower limbs. The disease-associated Hsp60-(p.Val98Ile) protein, encoded by the c.292G>A HSPD1 allele, has reduced chaperonin activity, but how its expression affects mitochondrial functions has not been investigated. We have studied mitochondrial function and expression of genes encoding mitochondrial chaperones and proteases in a human lymphoblastoid cell line and fibroblast cells from a patient who is heterozygous for the c.292G>A HSPD1 allele. We found that both the c.292G>A RNA transcript and the corresponding Hsp60-(p.Val98Ile) protein were present at comparable levels to their wild-type counterparts in SPG13 patient cells. Compared with control cells, we found no significant cellular or mitochondrial dysfunctions in SPG13 patient cells by assessing the mitochondrial membrane potential, cell viability, and sensitivity toward oxidative stress. However, a decreased expression of the mitochondrial protein quality control proteases Lon and ClpP, both at the RNA and protein level, was demonstrated in SPG13 patient cells. We propose that decreased levels of mitochondrial proteases Lon and ClpP may allow Hsp60 substrate proteins to go through more folding attempts instead of being prematurely degraded, thereby supporting productive folding in cells with reduced Hsp60 chaperonin activity. In conclusion, our studies with SPG13 patient cells expressing the functionally impaired mutant Hsp60 chaperonin suggest that reduction of the degradative activity of the protein quality control system may represent a previously unrecognized cellular adaptation to reduced chaperone function.

Pseudomonas fluorescens DR54 Reduces Sclerotia Formation, Biomass Development, and Disease Incidence of Rhizoctonia solani Causing Damping-Off in Sugar Beet.

Effects of the biocontrol strain, Pseudomonas fluorescens DR54, on growth and disease development by Rhizoctonia solani causing damping-off in sugar beet were studied in soil microcosms and in pot experiments with natural, clay-type soil. In pot experiments with P. fluorescens DR54-treated seeds, significantly fewer Rhizoctonia-challenged seedlings showed damping-off symptoms than when not inoculated with the biocontrol agent. In the rhizosphere of P. fluorescens DR54 inoculated seeds, the bacterial inoculant was present in high numbers as shown by dilution plating and immunoblotting. By the ELISA antibody technique and direct microscopy of the fungal pathogen grown in soil microcosms, it was shown that the presence of P. fluorescens DR54 on the inoculated seeds had a strong inhibitory effect on development of both mycelium biomass and sclerotia formation by R. solani. In the field experiment, plant emergence was increased by treatment with P. fluorescens DR54 and the inoculant was found to be the dominating rhizosphere colonizing pseudomonad immediately after seedling emergence.

[Atypical cervix uteri smears--consequences?]. / Cytologisk atypi i cervix uteri--konsekvens?

Among 37,992 cervical smears (725 (1.9%)) were found to be atypical. All atypial smears were referred for colposcopically guided biopsies and cervical abrasio within three months. This is an expensive and cumbersome procedure. In order to obtain a more differentiated follow-up procedure the atypical smears were divided into two groups without knowledge of the later histological diagnosis on biopsy: "Atypia, probably reactive" and "atypia, probably CIN (cervical intraepithelial neoplasia)". In the latter group the subsequent biopsies showed significantly more CIN than in the former (60.4% against 15.7%). We find it useful to divide the atypical smears into two groups in our daily routine work with a different follow-up procedure: "Atypia, probably reactive" to be followed by a repeat smear and "atypia, probably CIN" to be followed by colposcopically guided biopsies and cervical abrasio.

Stereomicroscopic demonstration of chorionic villi: differentiation between miscarriage and ectopic pregnancy.

OBJECTIVE: To evaluate direct peroperative stereomicroscopic examination of endometrial curettings in the differentiation between miscarriage and ectopic pregnancy. DESIGN: A prospective consecutive controlled study. SETTING: Odense University Hospital, Odense, Denmark. SUBJECTS: One hundred and fifty-nine women with vaginal bleeding and/or abdominal pain in early pregnancy and no fetus seen on ultrasound. MAIN OUTCOME MEASURES: The results of stereomicroscopy were compared with the histological diagnoses. RESULTS: There was 90% (95% CI, 84-94%) agreement between the stereomicroscopic and histological examinations. Fifteen per cent had an ectopic pregnancy. The sensitivity of stereomicroscopy as a marker of ectopic pregnancy was 92% (73-99%), the specificity 94% (88-97%). The predictive value of a positive test was 73% (54-88%) and that of a negative test 98% (94-100%). CONCLUSION: Direct peroperative stereomicroscopy of endometrial curettings is a valuable diagnostic tool for immediate differentiation between miscarriage and ectopic pregnancy.

Past, present, and future of psychiatry in New Jersey.

Society faces moral and practical choices of treatment for mental illness: warehousing, neglect, or appropriate treatment. Mental and physical health care must be available to all Americans. There must be a balance between cost containment and patient needs.

[Ultrasonically guided Biopty-biopsy of focal liver processes]. / Ultralydvejledt Biopty-biopsi af fokale leverprocesser.

During a period of three years, 51 patients with focal hepatic changes were submitted to 55 ultrasonically guided Biopty-biopsies. Histological diagnoses could be established in 45 patients at the first biopsy which corresponds to a diagnostic certainty of 88.2% Histological diagnoses were established in 49 patients which corresponds to a certainty of 96%. The frequency of complications was 3.9%. Biopty-biopsy is recommended as a good method because it is easy to carry out and provides just as good results as other methods of biopsy. In addition, it can provide more histological information than aspiration biopsies which are, however, somewhat cheaper.

[Comparison of endometrial changes in extra and intrauterine pregnancies. A clinical patho-anatomic study]. / Sammenligning af endometrieforandringer ved intra- og ekstrauterin graviditet. Klinisk pato-anatomisk undersøgelse.

Endometrial scrapings from 3 x 50 patients with spontaneous abortions (SA), terminations of pregnancy (PA) and extrauterine pregnancies (EG), respectively, were examined and compared with the clinical conditions. Fibrinoid deposits and isolated cytokeratine-positive cells in the decidua were only observed in cases of uterine pregnancy (IG). Arias-Stella's phenomenon in combination with decidua was observed equally frequently in IG and EG. Decidual reaction in the endometrium was observed in all of the patients with IG in contrast to the group with EG in which approximately 1/3 did not show the decidual reaction. Absence of the decidual reaction with or without Arias-Stella's phenomenon in pregnant women is, therefore, evidence of EG.

Broad ligament mucinous and serous cystadenomas of borderline malignancy.

The clinical and pathological findings including light microscopic and ultrastructural features of two cases of borderline mucinous and serous cystadenomas that originated in the broad ligament are reported. The tumors did not involve the oviduct or ovary. They probably arose in pre-existing cysts of mesothelial and paramesonephric (primary Müllerian) origin. These rare tumors bear a close resemblance to the borderline epithelial tumors of the ovary and the same prognostic criteria may be applicable to the lesions presented here.