Cardiac stress test is normal in pre‐motor Parkinson's disease

Cardiac sympathetic denervation is an early nonmotor feature of Parkinson's disease (PD). The aim of the current study was to trace evidence for cardiac dysfunction abnormalities in the premotor phase of PD. We retrospectively reviewed treadmill ergometric tests of a large cohort (n = 16,841) between 2000 and 2012, that attended the Executive Screening Survey (ESS) at Sheba Medical Center. Heart rate and blood pressure profiles as well as exercise capacity were compared between subjects who later developed PD and age‐ and sex‐matched subjects (ratio 1:2) who did not. We identified 28 subjects (24 males) who developed PD at follow‐up. The PD group was older than the group of subjects who did not develop PD on first ergometric test (64.82 ± 8.82 vs. 48.91 ± 10.60 years, P < 0.001). The time between the first ergometric test and motor symptoms onset was 4.64 ± 2.86 years. Patients who later developed PD had lower maximal heart rate (P < 0.001) and lower heart rate reserve than healthy controls (P < 0.001); however, compared with age‐ and sex‐matched subjects, subjects who developed PD had similar exercise capacity and heart rate profile during rest, exercise, and recovery, even 1 year before diagnosis. In this study, we did not detect significant signs of sympathetic dysfunction during the premotor phase of PD. © 2014 International Parkinson and Movement Disorder Society     

Chronic and cyclical neuronal loss in hippocampal slice cultures following transient inhibition of the type 1 isoform of superoxide dismutase

Increased oxidative stress contributes to chronic neurodegenerative diseases, yet the underlying mechanisms are poorly understood. Hippocampal slice cultures prepared from 20-30-day-old mice or rats were used to model chronic neuronal loss following oxidative stress. Neuronal loss was initiated by inhibition of the antioxidant enzyme, superoxide dismutase type 1 (SOD1), using the copper chelator diethyldithiocarbamate (DDC). Continuous DDC treatment of slice cultures induced delayed neuronal loss beginning at 9 days of treatment that lasted for over 4 weeks. Neuronal loss was not uniform, rather it was cyclic: peaking at days 9-13 and at days 19-21 after DDC exposure. Neuronal loss was significantly attenuated in slice cultures that overexpress SOD1, suggesting that SOD1 inhibition was responsible. Inhibitors of nitric oxide synthase also attenuated DDC-induced neuronal loss. Chronic neuronal loss, however, did not require continuous SOD1 inhibition. Application of DDC for 13 days resulted in loss of SOD1 activity. Removal of DDC restored SOD1 activity, yet the cycles of cell loss continued until no neurons remained. Astrocyte activation was observed following the second peak of neuronal loss. Media conditioned by cultures following DDC removal induced neuronal loss and microglial activation in recipient cultures. These data suggest that slice cultures released soluble neurotoxic factor(s) following DDC removal. These data also suggest that a transient reduction of SOD1 activity leads to chronic loss of hippocampal neurons. This neuronal loss may be mediated by soluble neurotoxic factor(s) and microglial activation. Cyclical neuronal loss may also underlie chronic neurodegeneration in vivo.     

Dietary lipids,prostaglandin E2 levels,and tooth movement in alveolar bone of rats

Summary A previous study showed that certain dietary lipids can alter arachidonic acid concentrations in alveolar bone. Because arachidonic acid is a precursor of prostaglandin (PG) E₂, which is known to play an important role in orthodontic tooth movement, the purpose of the present study was to determine the effect of dietary lipids on PGE₂ levels and tooth movement. Two groups of male Sprague-Dawley rats (20/group) were fed nutritionally adequate purified diets containing 10% corn oil (group I, rich in n-6 fatty acids) or 9% ethyl ester concentrate of n-3 fatty acids + 1% corn oil (group II rich in n-3 fatty acids). After 5 weeks of feeding the diets, orthodontic force of 56 g was applied to the maxillary incisors to tip them distally. Prior to killing the rats at day 4 and 8 of orthodontic force application, tooth movement was measured by computerized image analysis. Premaxillae were dissected out free of soft tissue and incisors. The alveolar bone was frozen in liquid nitrogen, pulverized, and lipids were extracted. The concentrations of arachidonic acid and fatty acid composition of total phospholipids were measured by gas chromatography. PGE₂ levels were measured by enzyme immunoassay. Arachidonic acid and PGE₂ concentration were significantly lower (P < 0.001) in alveolar bone of rats in group II than in group I. The tooth movement was also significantly lower (P < 0.02) in group II than in group I at both 4 and 8 days. The results suggest that PGE₂ levels in alveolar bone and orthodontic tooth movement can be affected by the type of dietary fat.Presented in part for the Hatton Award Competition at the International Association for Dental Research Meeting, Chicago, Illinois, March 10–14, 1993.     

An acoustic-speech study of patients who received orthognathic surgery

Several reports have suggested that orthognathic surgery may influence speech patterns. The purpose of this study was to examine the formant frequency changes of speech following orthognathic surgery in patients whose speech was considered perceptually normal preoperatively and postoperatively. Speech samples were obtained from five patients (three patients with Class II, Division 1 malocclusions and two patients with Class III malocclusions). Significant second-formant frequency shifts were found for the vowel 'e' (as in 'seat'); however, only minor second-formant frequency variations were found for the vowels 'a' (as in 'sat') and 'u' (as in 'suit'). The pattern of formant frequencies before and after surgical treatment suggested that the speakers adjusted their articulation to accommodate the orthognathic surgery. Overall, the data from this study indicate that speech patterns may be reorganized after orthognathic surgery even though speech remains perceptually "normal."     

Protein-energy malnutrition in rats during pregnancy modifies the effects of caffeine on fetal bones

The mandibles and long bones of newborn rats were analyzed for the effects of maternal caffeine consumption and protein-energy malnutrition. On d 13 of gestation, dams were randomly picked and divided into four groups. Group 1 received a 20% protein diet ad libitum. Group 2 was pair-fed with group 1 a 20% protein diet with a caffeine supplement (2 mg/100 g body wt). Group 3 received a 6% protein diet ad libitum. Group 4 was pair-fed with group 3 a 6% protein diet with caffeine. Within 8 h of delivery, all pups were weighted. Randomly selected pups were injected with 14C proline to study collagen synthesis of bones. Other pups were injected with 45Ca to study mineralization of bones. Although the average litter size from the 20% protein groups with or without caffeine did not show much variation, fetal resorption and stillbirths were higher in litters from group 4 compared to those from group 3. The mandibular weights of pups from group 2 was less than those from group 1, whereas weight of long bones of those from group 4 was heavier. The rate of collagen synthesis and calcium content of the mandible of group 4 and 45Ca uptake of the mandible of groups 2 and 4 were greater than that of the corresponding noncaffeine group. The rate of collagen synthesis, hydroxyproline content, 45Ca uptake and calcium content of the long bones of groups 2 and 4 were greater than that of the noncaffeine groups. The findings suggest that nutritional factors and the effects of caffeine are closely interrelated in the growth and development of the fetus and bone in newborn rats.     

Interobserver reliability in xeroradiographic cephalometry.

Observer agreement on cephalometric landmarks was compared between xeroradiographs and conventional radiographs of twenty-nine patients. Of fourteen landmarks evaluated, four (condylion, infradentale, Ptm, and ANS) demonstrated clinical significance in favor of the xeroradiograph. In addition, six other landmarks favored the xeroradiograph but not to the degree of statistical significance.     

Cyclin E deregulation is an early event in the development of breast cancer

Cyclin E has been shown to be overexpressed in some human breast cancers, however, data to support deregulation of cyclin E as an early event in human mammary tumor development is lacking. We analyzed surgical specimens from 183 patients with breast carcinomas and evaluated cyclin E expression in areas of invasive carcinoma, adjacent carcinoma in situ (CIS), and non-neoplastic breast parenchyma. Overexpression of cyclin E was seen in one-third of invasive carcinoma samples, one-third of the CIS component and nearly half of the non-neoplastic breast epithelial cells adjacent to carcinoma (44% vs. 33%, P ≤ 0.05). Nuclear labeling for cyclin E was highly concordant between areas of in invasive carcinoma, CIS and non-neoplastic breast epithelial cells from the same patient (P < 0.0001). Localization of cyclin E to the cytoplasm was seen in a small proportion of tumor samples. Our findings suggest that cyclin E deregulation is an early event in the progression from histologically benign mammary epithelial cells to invasive carcinoma and occurs through both overexpression and altered cellular localization.