Could dietary erucic acid lower risk of brain tumors? An epidemiological look to Chinese population with implications for prevention and treatment.

Erucic acid, an omega-9 monounsaturated fatty acid present in Brassicaceae plants (rapeseed and mustard oils) is highly consumed by the Chinese population and according to several global survey studies, its highest levels are encountered in the Chinese women's milk. Erucic acid is an activating ligand of the transcription factor PPARδ and an inhibitor of the transcriptional activity of PPARγ, which drive tumorigenesis of glioblastomas and medulloblastomas. In this theoretical review, we propose that erucic acid in diet may associate with the risk of brain tumors. High grade brain tumors including medulloblastomas in children and glioblastomas in adults have devastating consequences for human health and the latter tumors are practically incurable. CONCORD-3 epidemiological study recently published in 2021 revealed a low ratio of medulloblastomas in the pediatric age group and also a low ratio of glioblastomas in adults in the Chinese population. It is certain that such profound differences can not be attributed to a single genetic factor or a single nurture pattern. It is very likely that multiple hereditary, nutritional and environmental factors are responsible for these lower ratios; yet here we propose that erucic acid may be one of the contributing factors. If future epidemiological studies and animal models show antitumor activity of erucic acid regarding brain neoplasias, it can be utilized as a preventive strategy for populations possessing very high risks to develop brain tumors such as those harbouring hereditary syndromes increasing the vulnerability to develop such malignancies.

Caprylic acid ameliorates rotenone induced inflammation and oxidative stress in the gut-brain axis in Zebrafish.

BACKGROUND: Dysfunction of the gastrointestinal tract (GIT) is one of the most common non-motor symptom of Parkinson's Disease (PD). Pathological processes causing PD were suggested to initiate in the enteric nervous system (ENS) and proceed to the central nervous system (CNS). There are studies showing that low-carbohydrate ketogenic diets can improve motor symptoms of PD. Caprylic acid (C8) is the principal fatty acid component of the medium-chain triglycerides in the ketogenic diets. In this study, we aimed to evaluate the effects of caprylic acid, in neurotoxin exposed zebrafish focusing on the relationship between intestinal and brain oxidative stress and inflammation. METHODS: Adult zebrafish were exposed to rotenone (5 µg/L) (R group) and caprylic acid (20 and 60 mg/mL) (L + HDCA and R + HDCA groups) for 30 days. At the end of 30 days locomotor activities were determined. Levels of lipid peroxidation (LPO), nitric oxide, glutathione and superoxide dismutase and glutathione S-transferase activities were determined by spectrophotometric methods and gene expressions of tnf⍺, il1, il6, il21, ifnÉ£ and bdnf were evaluated by RT-PCR in the brain and intestinal tissues of zebrafish. RESULTS: Caprylic acid ameliorated LPO, NO, SOD and the expressions of tnf⍺, il1, il6, il21, ifnÉ£ and bdnf in brain and intestines. Locomotor activities were only ameliorated in high dose R + HDCA group. CONCLUSIONS: Caprylic acid ameliorated the neurotoxin-induced oxidative stress and inflammation both in the brain and intestines and enhanced locomotor activity in zebrafish.

From epidemiology and neurometabolism to treatment: Vitamin D in pathogenesis of glioblastoma Multiforme (GBM) and a proposal for Vitamin D + all-trans retinoic acid + Temozolomide combination in treatment of GBM.

Here we review tumoricidal efficacy of Vitamin D analogues in glioblastoma multiforme (GBM) and potential synergisms with retinoic acid and temozolomide based on epidemiological and cellular studies. Epidemiological data suggest that winter birth is associated with higher risk of GBM, and GBM debulking in the winter enhanced mortality, which may relate with lower exposure to sunlight essential to convert cholecalciferol to Vitamin D. Comparative studies on blood bank specimens revealed that higher prediagnosis levels of calcidiol are associated with lower risk of GBM in elderly men. Supplemental Vitamin D reduced mortality in GBM patients in comparison to nonusers. Expression of Vitamin D Receptor is associated with a good prognosis in GBM. Conversely, Vitamin D increases glial tumor synthesis of neutrophins NGF and NT-3, the low affinity neurotrophin receptor p75NTR, IL-6 and VEGF, which may enhance glioma growth. Antitumor synergisms between temozolomide and Vitamin D and Vitamin D with Vitamin A derivatives were observed. Hence, we hypothesize that Calcitriol + ATRA (All-Trans Retinoic Acid) + Temozolomide - CAT combination might be a safer approach to benefit from Vitamin D in the management of high-grade glial tumors. Adding acetazolomide to this protocol may reduce the risk of pseudotumor cerebri, as both Vitamin D and Vitamin A excess may cause intracranial hypertension; this approach may provide further benefit as acetazolomide also exhibits anticancer activity.

Pomegranate extract: a potential protector against aminoglycoside ototoxicity.

OBJECTIVE: To investigate the effectiveness of pomegranate extract as protection against aminoglycoside ototoxicity. DESIGN: Prospective, randomised, controlled, experimental study. SUBJECTS: Eighteen Wistar albino rats were randomly allocated to 5 days of either: saline injections; gentamicin injections; or pomegranate extract (100 µl/day via gavage) plus gentamicin injections. Distortion product otoacoustic emissions were tested before treatment and on day 3. After treatment, reactive oxygen species levels were measured in each rat's right cochlea and right kidney via chemiluminescence. RESULTS: Baseline emission amplitudes were similar. Post-treatment emissions differed significantly in the two treatment groups (p < 0.001). Cochlear reactive oxygen species levels were significantly higher in the gentamicin group (mean ± standard deviation, 316.6 ± 36.5 relative light units per mg) than the gentamicin plus pomegranate extract group (240 ± 24.6 relative light units per mg) (p = 0.004); control group levels were 119.1 ± 10.3 relative light units per mg. Renal reactive oxygen species levels were similar for the control and gentamicin plus pomegranate extract groups (p = 0.59) but much higher in the gentamicin group (p = 0.004). CONCLUSION: Concurrent systemic pomegranate extract administration reduced reactive oxygen species level increases and otoacoustic emission changes, following aminoglycoside injection.

Antioxidant effect of pomegranate extract in reducing acute inflammation due to myringotomy.

OBJECTIVE: To assess the effect of pomegranate extract on acute inflammation due to myringotomy. DESIGN: Prospective, randomised study. SUBJECTS: Thirty Sprague-Dawley rats were divided into three groups. Group one constituted controls. Group two underwent myringotomy. Group three underwent myringotomy and also received 100 µl/day pomegranate extract, via gavage, one day before and two days after surgery. Following sacrifice 48 hours after myringotomy, the animals' right ears were used to determine the concentration of reactive oxygen species, using the chemiluminescence method; left ears were used for histological study. RESULTS: Reactive oxygen species levels were significantly decreased in group three compared with group two (p < 0.01). The density of inflammatory cells in group three was significantly less than that in group two (p < 0.01). Lamina propria thickness and vessel density were also significantly decreased in group three compared with group two (p < 0.01). CONCLUSION: Our results indicate that oral pomegranate extract decreases reactive oxygen species concentration and acute inflammation in the tympanic membrane after myringotomy.

Atorvastatin has cardiac safety at intensive cholesterol-reducing protocols for long term, yet its cancer-treatment doses with chemotherapy may cause cardiomyopathy even under coenzyme-Q10 protection.

Statins provide strong clinical benefits via reducing stroke deaths, and they are also considered for tumor reduction and chemo-sensitization. High dose atorvastatin in adults (80 mg daily, approx. 1 mg/kg) is proven to afford greater protection against cardiac deaths than does a standard lipid-lowering dose in coronary syndrome. For cancer trials, mega doses up to 30 mg/kg have been used for short term treatments but neither a high nor a mega-dose of atorvastatin has been tested for long term cardiac safety. This may be of special concern, since some animal studies showed deleterious effects of statins on cardiac tissue, which may be related with coenzymeQ (CoQ) depletion. We performed an electron microscopic analysis of rat hearts after low, high-or mega-dose atorvastatin therapy and with or without MNU (methyl-nitrosourea)-stress. MNU + daily high dose atorvastatin treatment for 13 months did not produce severe cardiac toxicity with CoQ. However, at mega doses (30 mg/kg) and with MNU, mitochondrial damage and myofibrillary disintegration was obvious. Strong proliferation of mitochondria under high dose atorvastatin therapy with CoQ may explain the lack of cardiotoxicity; and this finding seems to parallel recent data that statins induce HNF-4 and PPAR-alpha, both responsible for mitochondria-proliferation. Employment of statins for tumor chemo-sensitization at high-dosage and for long term treatments may require strategies to direct the mevalonate-entry differentially into cardiac and tumor cells and to develop a protocol analogous to folic acid salvage of methotrexate toxicity.

Physical therapy in a patient with bilateral obturator nerve paralysis after surgery. A case report.

Obturator nerve injury can result from surgical procedures. Bilateral obturator nerve injury developed in our patient as a result of edema in the obturator fossa after a debulking operation. In the postoperative period, neuromuscular electrical stimulation, electromyographic (EMG) biofeedback, exercise and a home treatment program were used as the physical therapy approach. The patient became symptom-free after the physiotherapy program.