Effect of Glucosamine on Intraocular Pressure and Risk of Developing Glaucoma.

PRCIS: Glucosamine supplementation is common but can be associated with increased intraocular pressure (IOP) and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted. BACKGROUND: The most frequently recommended slow-acting medication for osteoarthritis symptoms is glucosamine, although its effectiveness is questionable. Widely used glucosamine sulfate supplements may increase IOP. METHODS: In the current study, we analyzed online databases such as UK Biobank, MedWatch, and FinnGen to evaluate the relationship between glucosamine and IOP and glaucoma. We included budesonide and fluticasone in the analysis for comparison since these drugs are associated with increased IOP. RESULTS: In UK Biobank subjects, glucosamine use was associated with increased corneal compensated IOP ( P =0.002, 2-tailed t test). This was also true in subjects without glaucoma ( P =0.002, 2-tailed t test). However, no significant association between glucosamine and IOP was detected in subjects with a diagnosis of glaucoma. In MedWatch, 0.21% of subjects taking glucosamine reported glaucoma, 0.29% of subjects using budesonide reported glaucoma, and 0.22% of subjects using fluticasone reported glaucoma. In contrast, 0.08% of subjects using any other drug reported glaucoma. This variability is significant ( P <0.001, 2-tailed Fisher exact test). Data from FinnGen on the risk of primary open angle glaucoma or glaucoma in subjects using glucosamine before the diagnosis of the disease revealed a significantly increased risk for both primary open angle glaucoma (hazard ratio: 2.35) and glaucoma (hazard ratio: 1.95). CONCLUSION: Glucosamine supplementation is common but can be associated with increased IOP and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted.

The Association Between Selenium, Selenoprotein P (SEPP1), Fluid Intelligence, and Exercise in the UK Biobank Cohort.

BACKGROUND: In the mouse hippocampus, exercise boosts neurogenesis. Increased levels of the selenium transport protein selenoprotein P (SEPP1) in the serum of exercised animals may contribute to the impact of exercise. SEPP1 is a protein that aids in the delivery of selenium to the brain. The effect of exercise on mouse brain precursor cell proliferation was diminished when SEPP1 or its receptor were genetically depleted. Selenium supplementation in the diet had the same effect as exercise in reducing some of the cognitive impairments associated with aging. METHODS: In the current analysis, we sought to determine the association of selenium, the SEPP1 gene, fluid intelligence, and exercise in the UK Biobank Cohort. We analyzed SEPP1 single nucleotide polymorphism (SNP) rs7579, a single nucleotide variation (SNV), position chr5:42800706, C > T, minor allele frequency T = 0.281. Its consequence is a 3'- UTR variant. The 3'-UTR contains regulatory regions that post-transcriptionally influence gene expression and is responsible for selenoprotein synthesis. SNP rs7579 has been implicated in multiple forms of cancer. The univariate general linear model of SPSS (IBM Corp., Armonk, NY) was used to rule out the effects of age, years of education, and vigorous activity on fluid intelligence score, with fluid intelligence score as the dependent variable, rs7579 genotype, and selenium supplements as fixed factors, and age, years of education, and vigorous activity as covariates. RESULTS: The effect of rs7579 genotype on fluid intelligence score was insignificant (p = 0.702). The effect of selenium supplements on fluid intelligence score was insignificant (p = 0.107). The interaction of rs7579 genotype and selenium supplements was insignificant (p = 0.911) and unrelated to the significant effects of age (p < 0.001), years of education (p < 0.001), and vigorous activity (p < 0.001) on fluid intelligence score.  Conclusion: Our multivariate analysis of SEPP1 genotype, selenium supplement use, and fluid intelligence scores is consistent with the negligible effect selenium supplements seem to have on cognition. Selenium is found in nuts, dairy products, and grains. These foods can provide sufficient selenium for health. Selenium supplements are not recommended.

Common drugs, vitamins, nutritional supplements and COVID-19 mortality.

The FDA has approved only one drug, remdesivir, for the treatment of COVID-19. The FDA has granted an emergency use authorization for the rheumatoid arthritis treatment drug, baricitinib (Olumiant), for the treatment of COVID-19 in some cases. For this reason, investigators have paid considerable attention to the association between commonly used drugs and the outcome of patients with COVID-19. Aspirin and ibuprofen have been reported to reduce the mortality rate. Omeprazole can increase mortality. In addition, some studies have demonstrated that famotidine diminishes mortality, while others have indicated that famotidine leads to a poorer prognosis. The present study used UK Biobank (UKB) data to assess the association of commonly used drugs with COVID-19 mortality. Data processing was performed on Minerva, a Linux mainframe with Centos 7.6. The UK Biobank Data Parser (ukbb_parser) was used, a python-based package that allows easy interfacing with the large UK Biobank dataset. The results revealed that aspirin and omeprazole were associated with an elevated mortality rate. Ibuprofen-related mortality was lower than laxative-related mortality. Aspirin users were also significantly older than other subjects. The association with mortality of cholesterol-lowering medications, blood pressure-lowering medications, hormone replacement and oral contraceptives in 134 female subjects revealed insignificant variability. The association of nutritional supplements in 238 subjects with mortality indicated that variability was insignificant. The lower mortality linked to the supplementation of vitamin D and vitamin B, presumably B complex, has been previously observed. On the whole, the present study demonstrates that although some of the associations described among drugs and COVID-19 are not novel, the utility of a new source, UKB, may prove to be useful in further examining these associations.

Transspinal delivery of drugs by transdermal patch back-of-neck for Alzheimer's disease: a new route of administration.

NSAIDs may prevent Alzheimer's disease (AD) but have failed as a treatment, possibly because only 1-2% of an oral NSAID dose reaches the brain. This minuscule dose is enough to have a preventative effect on Alzheimer's disease but not to treat it. We propose a new route of administration for drugs to treat AD: transspinal delivery by transdermal patch over the back-of-neck/cervical spine. The drug would diffuse from the patch through the intervertebral spaces, penetrate the dura, enter the CSF, and reach the brain. For example, diclofenac from a transdermal patch over the back of neck should readily penetrate the dura mater to reach the CSF and brain; since the analgesic ziconotide, and antisense molecules for treating spinal muscular atrophy in children and Huntington's disease, are delivered intrathecally and readily enter the brain. In addition to NSAIDs, an anticancer drug, paclitaxel, has considerable potential as an AD treatment. Paclitaxel is administered IV. But the blood-brain penetration of paclitaxel is poor and paclitaxel has systemic side effects such as anemia, leukopenia, peripheral neuropathy, etc. A high dose of paclitaxel might be administered to the brain by transdermal patch over the back of the neck/cervical spine while avoiding the systemic side effects. A transdermal patch over the cervical spine could revolutionize the drug therapy of AD, and probably other neurodegenerative/neuropsychiatric diseases as well.

Urinary symptom flare after brachytherapy for prostate cancer is associated with erectile dysfunction and more urinary symptoms before implantation.

OBJECTIVE: To examine the relationship of 'symptom flare' with sexual function and lower urinary tract symptoms (LUTS) before brachytherapy, as we noted that after brachytherapy for prostate cancer, some patients had recurrent LUTS after an asymptomatic period; this secondary exacerbation of symptoms ('symptom flare') occurred at approximately 2 years after implantation and was transient in most patients. PATIENTS AND METHODS: In all, 854 patients with organ-confined prostate carcinoma had transrectal ultrasonography-guided transperineal 125I interstitial brachytherapy of the prostate gland between June 1991 and September 2002, and were considered candidates for this study. Detailed information on urinary function was self-administered and prospectively collected before treatment and at intervals using the International Prostate Symptom Score (IPSS). Sexual function was evaluated with the Sexual Health Inventory for Men (SHIM), a five-question, self-administered diagnostic test that can help to indicate the presence or absence of erectile dysfunction (ED). We used previously established criteria to estimate the risk of prostate-specific antigen (PSA) failure by dividing the men into three risk groups, i.e. low-risk, with a PSA level of < or = 10 ng/mL, stage < or = T2a, Gleason < or = 6; medium-risk, with a PSA level of < or = 15 ng/mL, Gleason 7 or stage T2b; and high-risk, with a PSA level of > 15 ng/mL, stage > T2b, or Gleason > or = 8. RESULTS: There was a significant association of flare with ED; men with flare reported significantly more ED than men without (P = 0.020). Men with high-risk disease reported more ED because they received more intensive treatment (hormones and increased radiation dose) than men with medium- or low-risk disease. To correct for this confounding factor, multivariate linear regression was used; the regression was significant overall (P < 0.001), and the effects of risk group (P < 0.001) and flare (P < 0.026) on SHIM score were significant and independent of each other. Flare was also significantly associated with a higher pre-implant IPSS; the probability of flare was 62% for a pre-implant IPSS of zero, to 94% for an IPSS of 30. CONCLUSIONS: Radiation reaction and radiation sensitivity contribute to ED and greater LUTS in men who have had brachytherapy for prostate cancer. This contribution is evident, e.g. in men with ataxia-telangiectasia (ATM) gene mutations. Sequence variants in the ATM gene, particularly those that encode for an amino-acid substitution, are associated with adverse radiotherapy responses among patients treated with 125I prostate brachytherapy. Our finding of the association of urinary symptom flare with ED suggests it would be worthwhile to determine whether sildenafil is as effective in men with flare, and if not, whether higher sildenafil doses would be of value. Alternatively, alpha1-selective adrenoceptor-blocking agents, e.g. terazosin, combined with sildenafil, might be of benefit. Also, patients with a high IPSS before brachytherapy can be warned that they have a greater risk of flare and ED.