PMID: 

Front Pharmacol. 2019 ;10:711. Epub 2019 Jun 27. PMID: 31316381

Abstract Title: 

Efficacy of a Combination of N-Palmitoylethanolamide, Beta-Caryophyllene, Carnosic Acid, and Myrrh Extract on Chronic Neuropathic Pain: A Preclinical Study.

Abstract: 

Neuropathic pain (NP) is a common public health problem that poses a major challenge to basic scientists and health-care providers. NP is a complex problem with an unclear etiology and an often-inadequate response to current medications. Despite the high number of drugs available, their limited pharmacological efficacy and side effects hamper their chronic use. Thus, the search for novel treatments is a priority. In addition to pharmaceuticals, natural extracts and food supplements are often used to help treating patients with NP. One such supplement is Noxiall, a commercially available combination of N-Palmitoylethanolamide (PEA), beta-caryophyllene; carnosic acid and myrrh. Here, we compare the efficacy of Noxiallto that of the medications gabapentin and pregabalin in the NP model of chronic constriction injury (CCI) using sciatic nerve ligation in mouse. Following CCI, mice developed a significant increase in mechanical allodynia and thermal hyperalgesia. Results showed that administration of either Noxiall, pregabalin, or gabapentin significantly attenuated mechanical allodynia. The magnitude of the Noxialleffect was comparable to that of gabapentin or pregabalin. In addition, co-administration of non-effective doses of pregabalin and Noxiallresulted in a significant decrease in NP, suggesting an additive efficacy. Noxiallwas efficacious also in reducing CCI-induced thermal hyperalgesia. These findings support the rationale of using natural remedies in conjunction with classical pharmacological agents to treat chronic NP.

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PMID: 

Biomolecules. 2019 Jul 31 ;9(8). Epub 2019 Jul 31. PMID: 31370242

Abstract Title: 

β-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-γ Receptors.

Abstract: 

β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals werethen randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-ĸB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.

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PMID: 

Int J Oncol. 2013 Oct ;43(4):1036-44. Epub 2013 Jul 22. PMID: 23877578

Abstract Title: 

Pooled analysis of case-control studies on acoustic neuroma diagnosed 1997-2003 and 2007-2009 and use of mobile and cordless phones.

Abstract: 

We previously conducted a case-control study of acoustic neuroma. Subjects of both genders aged 20-80 years, diagnosed during 1997-2003 in parts of Sweden, were included, and the results were published. We have since made a further study for the time period 2007-2009 including both men and women aged 18-75 years selected from throughout the country. These new results for acoustic neuroma have not been published to date. Similar methods were used for both study periods. In each, one population-based control, matched on gender and age (within five years), was identified from the Swedish Population Registry. Exposures were assessed by a self-administered questionnaire supplemented by a phone interview. Since the number of acoustic neuroma cases in the new study was low we now present pooled results from both study periods based on 316 participating cases and 3,530 controls. Unconditional logistic regression analysis was performed, adjusting for age, gender, year of diagnosis and socio-economic index (SEI). Use of mobile phones of the analogue type gave odds ratio (OR) = 2.9, 95% confidence interval (CI) = 2.0-4.3, increasing with>20 years latency (time since first exposure) to OR = 7.7, 95% CI = 2.8-21. Digital 2G mobile phone use gave OR = 1.5, 95% CI = 1.1-2.1, increasing with latency>15 years to an OR = 1.8, 95% CI = 0.8-4.2. The results for cordless phone use were OR = 1.5, 95% CI = 1.1-2.1, and, for latency of>20 years, OR = 6.5, 95% CI = 1.7-26. Digital type wireless phones (2G and 3G mobile phones and cordless phones) gave OR = 1.5, 95% CI = 1.1-2.0 increasing to OR = 8.1, 95% CI = 2.0-32 with latency>20 years. For total wireless phone use, the highest risk was calculated for the longest latency time>20 years: OR = 4.4, 95% CI = 2.2-9.0. Several of the calculations in the long latency category were based on low numbers of exposed cases. Ipsilateral use resulted in a higher risk than contralateral for both mobile and cordless phones. OR increased per 100 h cumulative use and per year of latency for mobile phones and cordless phones, though the increase was not statistically significant for cordless phones. The percentage tumour volume increased per year of latency and per 100 h of cumulative use, statistically significant for analogue phones. This study confirmed previous results demonstrating an association between mobile and cordless phone use and acoustic neuroma.

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PMID: 

Asian Pac J Cancer Prev. 2012 ;13(11):5857-63. PMID: 23317269

Abstract Title: 

Changes in brain glioma incidence and laterality correlates with use of mobile phones–a nationwide population based study in Israel.

Abstract: 

INTRODUCTION: Mobile phones are in extensive use worldwide and concerns regarding their role in tumor formation were raised. Over the years multiple studies were published in order to investigate this issue using several approaches. The current study looks at secular trends of brain gliomas (low and high grade) incidence and changes in tumor's laterality over 30 years in a population extensively using this technology with a possible correlation to the spread of use of mobile phones.MATERIALS AND METHODS: All brain gliomas that were diagnosed from 1980-2009 were included and subdivided into two groups–low and high grade. Secular and periodic time trend analyses of incidence rates and changes in laterality were performed. Preferred side of head using mobile phones was assessed with a questionnaire in a sample of adult individuals.RESULTS: A decrease in incidence of low grade giomas (LGG) that correlated with introduction of mobile technology was found from 2.57, 2.34 and 2.79 for every 100,000 in the period 1980 to the end of 1994 to 1.72, 1.82 and 1.57, respectively, over the last three 5-years periods (1995-2009). High-grade glioma incidences increased significantly from 1980-2009 but in the period after mobile phones were introduced (1994-2009) a lower, non significant, rate of increase was observed in males and a lower one (significant) in females. A shift towards left sided tumor location for all adult gliomas combined and separately for LGG and HGG was noted from 1995 onward. The shift was more marked for those who were diagnosed in ages 20-49 (p=0.03).CONCLUSIONS: We found a statistically significant decrease in LGG's over 30-years period that correlates with introducing of mobile phones technology and a shift in laterality towards left-sided tumors, the latter occurred in both low and high-grade gliomas.

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PMID: 

Case Rep Med. 2013 ;2013:354682. Epub 2013 Sep 18. PMID: 24151509

Abstract Title: 

Multifocal Breast Cancer in Young Women with Prolonged Contact between Their Breasts and Their Cellular Phones.

Abstract: 

Breast cancer occurring in women under the age of 40 is uncommon in the absence of family history or genetic predisposition, and prompts the exploration of other possible exposures or environmental risks. We report a case series of four young women-ages from 21 to 39-with multifocal invasive breast cancer that raises the concern of a possible association with nonionizing radiation of electromagnetic field exposures from cellular phones. All patients regularly carried their smartphones directly against their breasts in their brassieres for up to 10 hours a day, for several years, and developed tumors in areas of their breasts immediately underlying the phones. All patients had no family history of breast cancer, tested negative for BRCA1 and BRCA2, and had no other known breast cancer risks. Their breast imaging is reviewed, showing clustering of multiple tumor foci in the breast directly under the area of phone contact. Pathology of all four cases shows striking similarity; all tumors are hormone-positive, low-intermediate grade, having an extensive intraductal component, and all tumors have near identical morphology. These cases raise awareness to the lack of safety data of prolonged direct contact with cellular phones.

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PMID: 

BMJ Open. 2013 Dec 30 ;3(12):e003836. Epub 2013 Dec 30. PMID: 24381254

Abstract Title: 

Subjective symptoms related to GSM radiation from mobile phone base stations: a cross-sectional study.

Abstract: 

OBJECTIVES: We performed a re-analysis of the data from Navarro et al (2003) in which health symptoms related to microwave exposure from mobile phone base stations (BSs) were explored, including data obtained in a retrospective inquiry about fear of exposure from BSs.DESIGN: Cross-sectional study.SETTING: LaÑora (Murcia), Spain.PARTICIPANTS: Participants with known illness in 2003 were subsequently disregarded: 88 participants instead of 101 (in 2003) were analysed. Since weather circumstances can influence exposure, we restricted data to measurements made under similar weather conditions.OUTCOMES AND METHODS: A statistical method indifferent to the assumption of normality was employed: namely, binary logistic regression for modelling a binary response (eg, suffering fatigue (1) or not (0)), and so exposure was introduced as a predictor variable. This analysis was carried out on a regular basis and bootstrapping (95% percentile method) was used to provide more accurate CIs.RESULTS: The symptoms most related to exposure were lack of appetite (OR=1.58, 95% CI 1.23 to 2.03); lack of concentration (OR=1.54, 95% CI 1.25 to 1.89); irritability (OR=1.51, 95% CI 1.23 to 1.85); and trouble sleeping (OR=1.49, 95% CI 1.20 to 1.84). Changes in -2 log likelihood showed similar results. Concerns about the BSs were strongly related with trouble sleeping (OR =3.12, 95% CI 1.10 to 8.86). The exposure variable remained statistically significant in the multivariate analysis. The bootstrapped values were similar to asymptotic CIs.CONCLUSIONS: This study confirms our preliminary results. We observed that the incidence of most of the symptoms was related to exposure levels-independently of the demographic variables and some possible risk factors. Concerns about adverse effects from exposure, despite being strongly related with sleep disturbances, do not influence the direct association between exposure and sleep.

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PMID: 

Molecules. 2019 May 19 ;24(10). Epub 2019 May 19. PMID: 31109132

Abstract Title: 

β-Caryophyllene as a Potential Protective Agent Against Myocardial Injury: The Role of Toll-Like Receptors.

Abstract: 

Myocardial infarction (MI) remains one of the major causes of mortality around the world. A possible mechanism involved in myocardial infarction is the engagement of Toll-like receptors (TLRs). This study was intended to discover the prospective cardioprotective actions ofβ-caryophyllene, a natural sesquiterpene, to ameliorate isoproterenol (ISO)-induced myocardial infarction through HSP-60/TLR/MyD88/NFκB pathway. β-Caryophyllene (100 or 200 mg/kg/day orally) was administered for 21 days then MI was induced via ISO (85 mg/kg, subcutaneous) on 20th and 21st days. The results indicated that ISO induced a significant infarcted area associated with several alterations in the electrocardiogram (ECG) and blood pressure (BP) indices and caused an increase in numerous cardiac indicators such as creatine phosphokinase (CPK), creatine kinase-myocardial bound (CK-MB),lactate dehydrogenase (LDH), and cardiac tropinine T (cTnT). In addition, ISO significantly amplified heat shock protein 60 (HSP-60) and other inflammatory markers, such as TNF-α, IL-Iβ, and NFκB, and affected TLR2 and TLR4 expression and their adaptor proteins; Myeloid differentiation primary response 88 (MYD88), and TIR-domain-containing adapter-inducing interferon-β (TRIF). On the other hand, consumption of β-caryophyllene significantly reversed the infarcted size, ECG and BP alterations, ameliorated the ISO elevation in cardiac indicators; it also notably diminished HSP-60, and subsequently TLR2, TLR4, MYD88, and TRIF expression, with a substantial reduction in inflammatory mediator levels. This study revealed the cardioprotective effect of β-caryophyllene against MI through inhibiting HSP-60/TLR/MyD88/NFκB signaling pathways.

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PMID: 

Environ Health. 2013 Oct 22 ;12:90. Epub 2013 Oct 22. PMID: 24148357

Abstract Title: 

The relationship between adolescents' well-being and their wireless phone use: a cross-sectional study.

Abstract: 

BACKGROUND: The exposure of young people to radiofrequency electromagnetic fields (RF-EMFs) has increased rapidly in recent years with their increased use of cellphones and use of cordless phones and WiFi. We sought to ascertain associations between New Zealand early-adolescents' subjective well-being and self-reported use of, or exposure to, wireless telephone and internet technology.METHODS: In this cross-sectional survey, participants completed questionnaires in class about their cellphone and cordless phone use, their self-reported well-being, and possible confounding information such as whether they had had influenza recently or had a television in the bedroom. Parental questionnaires provided data on whether they had WiFi at home and cordless phone ownership and model. Data were analysed with Ordinal Logistic Regression adjusting for common confounders. Odds ratios (OR) and 95% confidence intervals were calculated.RESULTS: The number and duration of cellphone and cordless phone calls were associated with increased risk of headaches (>6 cellphone calls over 10 minutes weekly, adjusted OR 2.4, CI 1.2-4.8;>15 minutes cordless use daily adjusted OR 1.74, CI 1.1-2.9)). Texting and extended use of wireless phones was related to having a painful 'texting' thumb). Using a wired cellphone headset was associated with tinnitus (adjusted OR 1.8, CI 1.0-3.3), while wireless headsets were associated with headache (adjusted OR 2.2, CI 1.1-4.5), feeling down/depressed (adjusted OR 2.0, CI 1.1-3.8), and waking in the night (adjusted OR 2.4, CI 1.2-4.8). Several cordless phone frequencies bands were related to tinnitus, feeling down/depressed and sleepiness at school, while the last of these was also related to modulation. Waking nightly was less likely for those with WiFi at home (adjusted OR 0.7, CI 0.4-0.99). Being woken at night by a cellphone was strongly related to tiredness at school (OR 3.49, CI 1.97-6.2).CONCLUSIONS: There were more statistically significant associations (36%) than could be expected by chance (5%). Several were dose-dependent relationships. To safeguard young people's well-being, we suggest limiting their use of cellphones and cordless phones to less than 15 minutes daily, and employing a speaker-phone device for longer daily use. We recommend parental measures are taken to prevent young people being woken by their cellphones.

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PMID: 

Neuroepidemiology. 2013 ;40(2):101-8. Epub 2012 Oct 24. PMID: 23095687

Abstract Title: 

Use of mobile and cordless phones and survival of patients with glioma.

Abstract: 

BACKGROUND: We analysed the survival of patients after glioma diagnosis in relation to the use of wireless phones.METHODS: All cases diagnosed between 1997 and 2003 with a malignant brain tumour (n = 1,251) in our case-control studies were included and followed from the date of diagnosis to the date of death or until May 30, 2012.RESULTS: For glioma, the use of wireless phones (mobile and cordless phones) gave a hazard ratio (HR) = 1.1 (95% confidence interval, CI = 0.9-1.2), with>10-year latency HR = 1.2 (95% CI = 1.002-1.5, p trend = 0.02). For astrocytoma grade I-II (low-grade), the results were, HR = 0.5 (95% CI = 0.3-0.9) and for astrocytoma grade IV (glioblastoma), HR = 1.1 (95% CI = 0.95-1.4), with>10 year latency HR = 1.3 (95% CI = 1.03-1.7). In the highest tertile (>426 h) of cumulative use, HR = 1.2 (95% CI = 0.95-1.5) was found for glioblastoma. The results were similar for mobile and cordless phones.CONCLUSIONS: Decreased survival of glioma cases with long-term and high cumulative use of wireless phones was found. A survival disadvantage for astrocytoma grade IV, but a survival benefit for astrocytoma grade I-II was observed which could be due to exposure-related tumour symptoms leading to earlier diagnosis and surgery in that patient group.

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PMID: 

Tumour Biol. 2014 Jan ;35(1):581-7. Epub 2013 Aug 27. PMID: 23975478

Abstract Title: 

Association between vestibular schwannomas and mobile phone use.

Abstract: 

Vestibular schwannomas (VSs) grow in the region where the energy from mobile phone use is absorbed. We examined the associations of VSs with mobile phone use. This study included 119 patients who had undergone surgical tumor removal. We used two approaches in this investigation. First, a case-control study for the association of mobile phone use and incidence of VSs was conducted. Both cases and controls were investigated with questions based on INTERPHONE guidelines. Amount of mobile phone use according to duration, daily amount, and cumulative hours were compared between two groups. We also conducted a case-case study. The location and volume of the tumors were investigated by MRI. Associations between the estimated amount of mobile phone use and tumor volume and between the laterality of phone use and tumor location were analyzed. In a case-control study, the odds ratio (OR) of tumor incidence according to mobile phone use was 0.956. In the case-case study, tumor volume and estimated cumulative hours showed a strong correlation (r(2) = 0.144, p = 0.002), and regular mobile phone users showed tumors of a markedly larger volume than those of non-regular users (p 

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