A pilot dose-finding study of Terazosin in humans.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ), an α-1 adrenergic receptor antagonist with a known efficacy in treating benign prostatic hypertrophy and hypertension, has shown potential in addressing energy metabolism deficits associated with PD due to its action on phosphoglycerate kinase 1 (PGK1). This study aimed to investigate the safety, tolerability, bioenergetic target engagement, and optimal dose of TZ in neurologically healthy subjects. Methods: Eighteen healthy men and women (60 - 85 years old) were stratified into two cohorts based on maximum TZ dosages (5 mg and 10 mg daily). Methods included plasma and cerebrospinal fluid TZ concentration measurements, whole blood ATP levels, 31 Phosphorous magnetic resonance spectroscopy for brain ATP levels, 18 F-FDG PET imaging for cerebral metabolic activity, and plasma metabolomics. Results: Our results indicated that a 5 mg/day dose of TZ significantly increased whole blood ATP levels and reduced global cerebral 18 F-FDG PET uptake without significant side effects or orthostatic hypotension. These effects were consistent across sexes. Higher doses did not result in additional benefits and showed a potential biphasic dose-response. Conclusions: TZ at a dosage of 5 mg/day engages its metabolic targets effectively in both sexes without inducing significant adverse effects and provides a promising therapeutic avenue for mitigating energetic deficiencies. Further investigation via clinical trials to validate TZ's efficacy and safety in neurodegenerative (i.e., PD) contexts is warranted.

The human subthalamic nucleus transiently inhibits active attentional processes.

The subthalamic nucleus (STN) of the basal ganglia is key to the inhibitory control of movement. Consequently, it is a primary target for the neurosurgical treatment of movement disorders like Parkinson's Disease, where modulating the STN via deep-brain stimulation (DBS) can release excess inhibition of thalamo-cortical motor circuits. However, the STN is also anatomically connected to other thalamo-cortical circuits, including those underlying cognitive processes like attention. Notably, STN-DBS can also affect these processes. This suggests that the STN may also contribute to the inhibition of non-motor activity, and that STN-DBS may cause changes to this inhibition. We here tested this hypothesis in humans. We used a novel, wireless outpatient method to record intracranial local field potentials (LFP) from STN DBS implants during a visual attention task (Experiment 1, N=12). These outpatient measurements allowed the simultaneous recording of high-density EEG, which we used to derive the steady-state visual evoked potential (SSVEP), a well-established neural index of visual attentional engagement. By relating STN activity to this neural marker of attention (instead of overt behavior), we avoided possible confounds resulting from STN's motor role. We aimed to test whether the STN contributes to the momentary inhibition of the SSVEP caused by unexpected, distracting sounds. Furthermore, we causally tested this association in a second experiment, where we modulated STN via DBS across two sessions of the task, spaced at least one week apart (N=21, no sample overlap with Experiment 1). The LFP recordings in Experiment 1 showed that reductions of the SSVEP after distracting sounds were preceded by sound-related γ-frequency (>60Hz) activity in the STN. Trial-to-trial modeling further showed that this STN activity statistically mediated the sounds' suppressive effect on the SSVEP. In Experiment 2, modulating STN activity via DBS significantly reduced these sound-related SSVEP reductions. This provides causal evidence for the role of the STN in the surprise-related inhibition of attention. These findings suggest that the human STN contributes to the inhibition of attention, a non-motor process. This supports a domain-general view of the inhibitory role of the STN. Furthermore, these findings also suggest a potential mechanism underlying some of the known cognitive side-effects of STN-DBS treatment, especially on attentional processes. Finally, our newly-established outpatient LFP recording technique facilitates the testing of the role of subcortical nuclei in complex cognitive tasks, alongside recordings from the rest of the brain, and in much shorter time than perisurgical recordings.

Resting-state EEG measures cognitive impairment in Parkinson's disease.

Cognitive dysfunction is common in Parkinson's disease (PD). We developed and evaluated an EEG-based biomarker to index cognitive functions in PD from a few minutes of resting-state EEG. We hypothesized that synchronous changes in EEG across the power spectrum can measure cognition. We optimized a data-driven algorithm to efficiently capture these changes and index cognitive function in 100 PD and 49 control participants. We compared our EEG-based cognitive index with the Montreal cognitive assessment (MoCA) and cognitive tests across different domains from National Institutes of Health (NIH) Toolbox using cross-validations, regression models, and randomization tests. Finally, we externally validated our approach on 32 PD participants. We observed cognition-related changes in EEG over multiple spectral rhythms. Utilizing only 8 best-performing electrodes, our proposed index strongly correlated with cognition (MoCA: rho = 0.68, p value < 0.001; NIH-Toolbox cognitive tests: rho ≥ 0.56, p value < 0.001) outperforming traditional spectral markers (rho = -0.30-0.37). The index showed a strong fit in regression models (R2 = 0.46) with MoCA, yielded 80% accuracy in detecting cognitive impairment, and was effective in both PD and control participants. Notably, our approach was equally effective (rho = 0.68, p value < 0.001; MoCA) in out-of-sample testing. In summary, we introduced a computationally efficient data-driven approach for cross-domain cognition indexing using fewer than 10 EEG electrodes, potentially compatible with dynamic therapies like closed-loop neurostimulation. These results will inform next-generation neurophysiological biomarkers for monitoring cognition in PD and other neurological diseases.

The impact of alpha-1-adrenergic receptor antagonists on the progression of Parkinson disease.

BACKGROUND: Alpha-1-adrenergic receptor antagonists (AARAs) are used in the treatment of benign prostatic hypertrophy. Some AARAs, such as terazosin, stimulate glycolysis and increase cellular adenosine triphosphate levels through activation of phosphoglycerate kinase 1 (PGK1), which has been suggested to be of therapeutic benefit in patients with Parkinson disease (PD). OBJECTIVE: This study aimed to determine whether exposure to PGK1-activating AARAs was associated with slower PD progression. METHODS: National Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000 to 2019 and were concurrently prescribed an AARA. Using a retrospective cohort design, the count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK1-activating AARA versus tamsulosin (an AARA without PKG1 stimulation), using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, nonmotor symptoms, and other potential complications as clinical markers for the progression of PD. RESULTS: A total of 127,142 patients initiated drug therapy for PD during the observation period, of whom 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n = 14,571) than tamsulosin (n = 9968) (incidence rate ratio [IRR] 0.80 [95% CI 0.77-0.83]). These results remained significant after adjustment for confounding factors (IRR 0.85 [95% CI 0.81-0.88]) and in sensitivity analyses. CONCLUSION: Patients prescribed a PGK1-activating AARA experienced fewer PD-related outcome events than patients prescribed tamsulosin. These results may indicate a role for terazosin and other PGK1 activators in slowing disease progression of PD; however, randomized controlled trials are needed.

Digital driving data can track driving exposure and quality of life in Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) impairs motor and non-motor functions. Driver strategies to compensate for impairments, like avoiding driving in risky environments, may reduce on-road risk at the cost of decreasing driver mobility, independence, and quality of life (QoL). It is unclear how PD symptoms link to driving risk exposure, strategies, and QoL. We assessed associations between PD symptoms and driving exposure (1) overall, (2) in risky driving environments, and (3) in relationship to QoL. METHODS: Twenty-eight drivers with idiopathic PD were assessed using the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and RAND 36-Item Short Form Health Survey (SF-36). Real-world driving was monitored for 1 month. Overall driving exposure (miles driven) and risky driving exposure (miles driven in higher risk driving environments) were assessed across PD symptom severity. High traffic, night, and interstate roads were considered risky environments. RESULTS: 18,642 miles (30,001 km) driven were collected. Drivers with PD with worse motor symptoms (MDS-UPDRS Part III) drove more overall (b = 0.17, P < .001) but less in risky environments (night: b = -0.35, P < .001; interstate roads: b = -0.23, P < .001; high traffic: b = -0.14, P < .001). Worse non-motor daily activities symptoms (MDS-UPDRS Part I) did not affect overall driving exposure (b = -0.05, P = .43) but did affect risky driving exposure. Worse non-motor daily activities increased risk exposure to interstate (b = 0.36, P < .001) and high traffic (b = 0.09, P = .03) roads while reducing nighttime risk exposure (b = -0.15, P = .01). Daily activity impacts from motor symptoms (MDS-UPDRS Part II) did not affect distance driven. Reduced driving exposure (number of drives per day) was associated with worse physical health-related QoL (b = 2.87, P = .04). CONCLUSIONS: Results provide pilot data revealing specific PD symptom impacts on driving risk exposure and QoL. Drivers with worse non-motor impairments may have greater risk exposure. In contrast, drivers with worse motor impairments may have reduced driver risk exposure. Reduced driving exposure may worsen physical health-related QoL. Results show promise for using driving to inform clinical care.

Real-World Driving Data Indexes Dopaminergic Treatment Effects in Parkinson's Disease.

Background: Driving is a complex, everyday task that impacts patient agency, safety, mobility, social connections, and quality of life. Digital tools can provide comprehensive real-world (RW) data on driver behavior in patients with Parkinson's disease (PD), providing critical data on disease status and treatment efficacy in the patient's own environment. Objective: This pilot study examined the use of driving data as a RW digital biomarker of PD symptom severity and dopaminergic therapy effectiveness. Methods: Naturalistic driving data (3974 drives) were collected for 1 month from 30 idiopathic PD drivers treated with dopaminergic medications. Prescriptions data were used to calculate levodopa equivalent daily dose (LEDD). The association between LEDD and driver mobility (number of drives) was assessed across PD severity, measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: PD drivers with worse motor symptoms based on self-report (Part II: P = 0.02) and clinical examination (Part III: P < 0.001) showed greater decrements in driver mobility. LEDD levels >400 mg/day were associated with higher driver mobility than those with worse PD symptoms (Part I: P = 0.02, Part II: P < 0.001, Part III: P < 0.001). Conclusions: Results suggest that comprehensive RW driving data on PD patients may index disease status and treatment effectiveness to improve patient symptoms, safety, mobility, and independence. Higher dopaminergic treatment may enhance safe driver mobility in PD patients with worse symptom severity.

Real-life consequences of cognitive dysfunction in Parkinson's disease.

While motor symptoms are the most recognized features of Parkinson's disease (PD), cognitive dysfunction is a key determinant of consequences of PD in real-life. In this chapter we review important domains where cognitive dysfunction negatively impacts the lives of people with PD (PwPD), such as difficulties in occupational and social life, and instrumental ADLs such as driving. Early loss of employment has important effects for PwPD, their families, and society. PwPD experience higher rates of family and social discord as well as important changes in their social roles. These processes are largely mediated through cognitive dysfunction, particularly difficulties processing and understanding emotions, decreased attention, and executive dysfunction. Cognitive dysfunction is also an important mediator of driving impairments, which contributes to decreased independence in PwPD. Finally, we briefly review the costs associated with cognitive impairment in PD. Both indirect and direct costs for PwPD with cognitive impairment are substantially higher than for PwPD with normal cognition.

A pilot to assess target engagement of terazosin in Parkinson's disease.

BACKGROUND: Impaired brain energy metabolism is a key feature of Parkinson's disease (PD). Terazosin (TZ) binds phosphoglycerate kinase 1 and stimulates its activity, which enhances glycolysis and increases ATP levels. Preclinical and epidemiologic data suggest that TZ may be neuroprotective in PD. We aimed to assess target engagement and safety of TZ in people with PD. METHODS: We performed a 12-week pilot study in people with PD. Participants were randomized to receive 5 mg TZ or placebo. Participants and study personnel were blinded. We assessed TZ target engagement by measuring brain ATP with 31P-magnetic resonance spectroscopy (MRS) and whole blood ATP with a luminescence assay. Robust linear regression models compared changes between groups controlling for baseline brain and blood ATP levels, respectively. We also assessed clinical measures of PD and adverse events. RESULTS: Thirteen participants were randomized. Mild dizziness/lightheadedness was more common in the TZ group, and three participants taking TZ dropped out because of dizziness and/or orthostatic hypotension. Compared to the placebo group, the TZ group had a significant increase in the ratio of ßATP to inorganic phosphate in the brain. The TZ group also had a significant increase in blood ATP levels compared to the placebo group (p < 0.01). CONCLUSIONS: This pilot study suggests that TZ may engage its target and change ATP levels in the brain and blood of people with PD. Further studies may be warranted to test the disease-modifying potential of TZ.

Approach to Cognitive Impairment in Parkinson's Disease.

Cognitive dysfunction is common in Parkinson's disease (PD) and predicts poor clinical outcomes. It is associated primarily with pathologic involvement of basal forebrain cholinergic and prefrontal dopaminergic systems. Impairments in executive functions, attention, and visuospatial abilities are its hallmark features with eventual involvement of memory and other domains. Subtle symptoms in the premotor and early phases of PD progress to mild cognitive impairment (MCI) which may be present at the time of diagnosis. Eventually, a large majority of PD patients develop dementia with advancing age and longer disease duration, which is usually accompanied by immobility, hallucinations/psychosis, and dysautonomia. Dopaminergic medications and deep brain stimulation help motor dysfunction, but may have potential cognitive side effects. Central acetylcholinesterase inhibitors, and possibly memantine, provide modest and temporary symptomatic relief for dementia, although there is no evidence-based treatment for MCI. There is no proven disease-modifying treatment for cognitive impairment in PD. The symptomatic and disease-modifying role of physical exercise, cognitive training, and neuromodulation on cognitive impairment in PD is under investigation. Multidisciplinary approaches to cognitive impairment with effective treatment of comorbidities, proper rehabilitation, and maintenance of good support systems in addition to pharmaceutical treatment may improve the quality of life of the patients and caregivers.

Cerebellar Transcranial Direct Current Stimulation in People with Parkinson's Disease: A Pilot Study.

People with Parkinson's disease (PwPD) often experience gait and balance problems that substantially impact their quality of life. Pharmacological, surgical, and rehabilitative treatments have limited effectiveness and many PwPD continue to experience gait and balance impairment. Transcranial direct current stimulation (tDCS) may represent a viable therapeutic adjunct. The effects of lower intensity tDCS (2 mA) over frontal brain areas, in unilateral and bilateral montages, has previously been explored; however, the effects of lower and higher intensity cerebellar tDCS (2 mA and 4 mA, respectively) on gait and balance has not been investigated. Seven PwPD underwent five cerebellar tDCS conditions (sham, unilateral 2 mA, bilateral 2 mA, unilateral 4 mA, and bilateral 4 mA) for 20 min. After a 10 min rest, gait and balance were tested. The results indicated that the bilateral 4 mA cerebellar tDCS condition had a significantly higher Berg Balance Scale score compared to sham. This study provides preliminary evidence that a single session of tDCS over the cerebellum, using a bilateral configuration at a higher intensity (4 mA), significantly improved balance performance. This intensity and cerebellar configuration warrants future investigation in larger samples and over repeated sessions.

Driving in Parkinson Disease.

Driving is impaired in most patients with Parkinson disease because of motor, cognitive, and visual dysfunction. Driving impairments in Parkinson disease may increase the risk of crashes and result in early driving cessation with loss of independence. Drivers with Parkinson disease should undergo comprehensive evaluations to determine fitness to drive with periodic follow-up evaluations as needed. Research in rehabilitation of driving and automation to maintain independence of patients with Parkinson disease is in progress.

Glucose-6-phosphate dehydrogenase, glutathione peroxidase, total glutatione and reduced nicotinamide adenine dinucleotide phosphate in milk cells of subclinical mastitic cows.

This study aimed to determine the levels of milk cell total protein (TP), reduced nicotinamide adenine dinucleotide phosphate (NADPH), total glutathione (tGSH), activities of glucose-6-phosphate dehydrogenase (G6PD) and glutathione peroxidase (GPx) in subclinical mastitic cows. Milk from each udder was collected and grouped by the California Mastitis Test. Then, a somatic cell count (SCC) was performed, and the groups were re-scored as control (5-87 × 103 cells), 1st group (154-381 × 103 cells), 2nd group (418-851 × 103 cells), 3rd group (914-1958 × 103 cells), and 4th group (2275-8528 × 103 cells). Milk cell TP, NADPH, tGSH levels, G6PD, and GPx activities were assessed. Microbiological diagnosis and aerobic mesophyle general organism (AMG, cfu/g) were also conducted. In mastitic milk, TP, NADPH, and tGSH levels, and G6PD and GPx activities were significantly reduced per cell (in samples of 106 cells). In addition, milk SCC was positively correlated with AMG (r=0.561, p⟨0.001), NADPH (r=0.380, p⟨0.01), TP (r=0.347, p⟨0.01) and G6PD (r=0.540, p⟨0.001). There was also positive correlation between NADPH (r=0.428, p⟨0.01), TP (r=0.638, p⟨0.001) and AMG. NADPH was positively correlated with TP (r=0.239, p⟨0.05), GPx (r=0.265, p⟨0.05) and G6PD (r=0.248, p=0.056). Total protein was positively correlated with tGSH (r=0.354, p⟨0.01) and G6PD (r=0.643, p⟨0.001). There was a negative correlation between tGSH and GPx activity (r=-0.306, p⟨0.05). The microbiological analysis showed the following ratio of pathogens: Coagulase-Negative Staphylococci 66.6%, Streptococcus spp 9.5%, Bacillus spp 9.5%, yeast 4.8%, and mixed infections 9.5%. As a conclusion, when evaluating the enzyme and oxidative stress parameters in milk, it is more suitable to assign values based on cell count rather than ml of milk. The linear correlation between the SCC and AMG, milk cell NADPH, TP and G6PD suggests that these parameters could be used as markers of mastitis.

Driving impairment and crash risk in Parkinson disease: A systematic review and meta-analysis.

OBJECTIVES: To provide the best possible evidence base for guiding driving decisions in Parkinson disease (PD), we performed a meta-analysis comparing patients with PD to healthy controls (HCs) on naturalistic, on-the-road, and simulator driving outcomes. METHODS: Seven major databases were systematically searched (to January 2018) for studies comparing patients with PD to HCs on overall driving performance, with data analyzed using random-effects meta-analysis. RESULTS: Fifty studies comprising 5,410 participants (PD = 1,955, HC = 3,455) met eligibility criteria. Analysis found the odds of on-the-road test failure were 6.16 (95% confidence interval [CI] 3.79-10.03) times higher and the odds of simulator crashes 2.63 (95% CI 1.64-4.22) times higher for people with PD, with poorer overall driving ratings also observed (standardized mean differences from 0.50 to 0.67). However, self-reported real-life crash involvement did not differ between people with PD and HCs (odds ratio = 0.84, 95% CI 0.57-1.23, p = 0.38). Findings remained unchanged after accounting for any differences in age, sex, and driving exposure, and no moderating influence of disease severity was found. CONCLUSIONS: Our findings provide persuasive evidence for substantive driving impairment in PD, but offer little support for mandated PD-specific relicensure based on self-reported crash data alone, and highlight the need for objective measures of crash involvement.

Cognitive impairment in Parkinson's disease: a report from a multidisciplinary symposium on unmet needs and future directions to maintain cognitive health.

People with Parkinson's disease (PD) and their care partners frequently report cognitive decline as one of their greatest concerns. Mild cognitive impairment affects approximately 20-50% of people with PD, and longitudinal studies reveal dementia in up to 80% of PD. Through the Parkinson's Disease Foundation Community Choice Research Award Program, the PD community identified maintaining cognitive function as one of their major unmet needs. In response, a working group of experts across multiple disciplines was organized to evaluate the unmet needs, current challenges, and future opportunities related to cognitive impairment in PD. Specific conference goals included defining the current state in the field and gaps regarding cognitive issues in PD from patient, care partner, and healthcare professional viewpoints; discussing non-pharmacological interventions to help maintain cognitive function; forming recommendations for what people with PD can do at all disease stages to maintain cognitive health; and proposing ideas for how healthcare professionals can approach cognitive changes in PD. This paper summarizes the discussions of the conference, first by addressing what is currently known about cognitive dysfunction in PD and discussing several non-pharmacological interventions that are often suggested to people with PD. Second, based on the conference discussions, we provide considerations for people with PD for maintaining cognitive health and for healthcare professionals and care partners when working with people with PD experiencing cognitive impairment. Furthermore, we highlight key issues and knowledge gaps that need to be addressed in order to advance research in cognition in PD and improve clinical care.

Longitudinal decline of driving safety in Parkinson disease.

OBJECTIVE: To longitudinally assess and predict on-road driving safety in Parkinson disease (PD). METHODS: Drivers with PD (n = 67) and healthy controls (n = 110) drove a standardized route in an instrumented vehicle and were invited to return 2 years later. A professional driving expert reviewed drive data and videos to score safety errors. RESULTS: At baseline, drivers with PD performed worse on visual, cognitive, and motor tests, and committed more road safety errors compared to controls (median PD 38.0 vs controls 30.5; p < 0.001). A smaller proportion of drivers with PD returned for repeat testing (42.8% vs 62.7%; p < 0.01). At baseline, returnees with PD made fewer errors than nonreturnees with PD (median 34.5 vs 40.0; p < 0.05) and performed similar to control returnees (median 33). Baseline global cognitive performance of returnees with PD was better than that of nonreturnees with PD, but worse than for control returnees (p < 0.05). After 2 years, returnees with PD showed greater cognitive decline and larger increase in error counts than control returnees (median increase PD 13.5 vs controls 3.0; p < 0.001). Driving error count increase in the returnees with PD was predicted by greater error count and worse visual acuity at baseline, and by greater interval worsening of global cognition, Unified Parkinson's Disease Rating Scale activities of daily living score, executive functions, visual processing speed, and attention. CONCLUSIONS: Despite drop out of the more impaired drivers within the PD cohort, returning drivers with PD, who drove like controls without PD at baseline, showed many more driving safety errors than controls after 2 years. Driving decline in PD was predicted by baseline driving performance and deterioration of cognitive, visual, and functional abnormalities on follow-up.

Separating the effect of reward from corrective feedback during learning in patients with Parkinson's disease.

Parkinson's disease (PD) is associated with procedural learning deficits. Nonetheless, studies have demonstrated that reward-related learning is comparable between patients with PD and controls (Bódi et al., Brain, 132(9), 2385-2395, 2009; Frank, Seeberger, & O'Reilly, Science, 306(5703), 1940-1943, 2004; Palminteri et al., Proceedings of the National Academy of Sciences of the United States of America, 106(45), 19179-19184, 2009). However, because these studies do not separate the effect of reward from the effect of practice, it is difficult to determine whether the effect of reward on learning is distinct from the effect of corrective feedback on learning. Thus, it is unknown whether these group differences in learning are due to reward processing or learning in general. Here, we compared the performance of medicated PD patients to demographically matched healthy controls (HCs) on a task where the effect of reward can be examined separately from the effect of practice. We found that patients with PD showed significantly less reward-related learning improvements compared to HCs. In addition, stronger learning of rewarded associations over unrewarded associations was significantly correlated with smaller skin-conductance responses for HCs but not PD patients. These results demonstrate that when separating the effect of reward from the effect of corrective feedback, PD patients do not benefit from reward.

Use, maintenance and dose effects of cognitive speed of processing training in Parkinson's disease.

INTRODUCTION: Recent research indicated that cognitive speed of processing training (SPT) improved Useful Field of View (UFOV) among individuals with Parkinson's disease (PD). The effects of SPT in PD have not been further examined. The objectives of the current study were to investigate use, maintenance and dose effects of SPT among individuals with PD. METHODS: Participants who were randomized to SPT or a delayed control group completed the UFOV at a six-month follow-up visit. Use of SPT was monitored across the six-month study period. Regression explored factors affecting SPT use. Mixed effect models were conducted to examine the durability of training gains among those randomized to SPT (n = 44), and training dose effects among the entire sample (n = 87). RESULTS: The majority of participants chose to continue to use SPT (52%). Those randomized to SPT maintained improvements in UFOV performance. A significant dose effect of SPT was evident such that more hours of training were associated with greater UFOV performance improvements. The cognitive benefits derived from SPT in PD may be maintained for up to three months. CONCLUSION: Future research should determine how long gains endure and explore if such training gains transfer.

Thiol/disulfide homeostasis in postmenopausal osteoporosis.

AIM: To evaluate the impact of postmenopausal osteoporosis on thiol/disulfide homeostasis. MATERIALS AND METHODS: A total of 75 participants were divided into two groups: Group 1 (n = 40) was composed of healthy postmenopausal women, and group 2 (n = 35) was composed of women with postmenopausal osteoporosis. Clinical findings and thiol/disulfide homeostasis were compared between the two groups. RESULTS: The disulfide/native thiol ratio was 8.6% ± 3.6 in group 1 and 12.7% ± 8.4 in group 2 (p = 0.04). The disulfide/native thiol percent ratio was significantly higher in group 2 after adjustment for the years since menopause and age (p < 0.05). The native thiol/total thiol percent ratio was 85.6% ± 4.8 in group 1 and 73.8% ± 24.9 in group 2 (p = 0.01). The native thiol/total thiol percent ratio was significantly lower in group 2 after adjustment for the years since menopause and age (p < 0.05). CONCLUSION: Thiol/disulfide homeostasis shifted to the disulfide side independent of age and years since menopause in postmenopausal osteoporosis.

Omega-3 prevents myelin degeneration in rat foetuses exposed to radiation.

The aim of this study is to investigate the protective effect of antioxidant omega-3 fatty acid (FA) on demyelinisation and degeneration of nerves in central and peripheral nervous systems (CNS and PNS) of rat foetuses. 38 pregnant rats weighing 140-155 g were used. Rats were divided into five groups. Group 1: 7 rats exposed to radiation treatment (RT) for 1 hour/day only; Group 2: 7 rats exposed to RT + Omega-3 FA (p.o.) for 1 hour/day; Group 3: 7 rats exposed to RT for 4 hours/day; Group 4: 7 rats exposed to RT + Omega-3 FA (p.o.) for 4 hours/day; and Group 5: 10 rats with no treatment. Nerve injury was induced by whole-body exposure to 20-µT magnetic field. Omega-3 FA was given orally at a dose of 50 mg/kg. After 18 days, foetuses were delivered by the milking method; CNS and PNS were taken out for pathological examination. The degeneration scores of Group 2 were significantly lower than those of Group 1, whereas the degeneration scores of Group 4 were significantly higher than those of Groups 1 and 3. In conclusion, radiation increases demyelinisation and degeneration of nerves in the rat foetuses' CNS and PNS. Omega-3 FA prevents myelin and nerve degeneration in rat foetuses in low-dose radiation exposure.