Article

Influence of various intensities of 528 Hz sound-wave in production of testosterone in rat’s brain and analysis of behavioral changes

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Abstract

Testosterone is a nuclear androgen receptor ligand that controls multiple pathways in brain. In addition to the active biosynthesis of steroids in classic steroidogenic organs such as gonads, adrenals and placenta, testosterone also produced in astrocyte cells of brain. Testosterone and its level must be regulated in brain; because, it directly and indirectly affects memory and several key behavioral characteristics. The significance of sound waves on key enzymes that regulate levels of testosterone in brain has not been investigated. The aim of our study was to examine physical stress of such as sound on induction behavioral changes in animal models. According to the current study, sound waves with 528 Hz frequency in 100 dB intensity induce testosterone production in brain by enhancing StAR and SF-1 and reducing P450 aromatase gene expression. Frequency of 528 Hz also reduces total concentration of reactive oxidative species in brain tissue. Prolonged exposure to this sound wave showed reduction of anxiety related behaviors in rats. The results reveal that reduced anxiety is related to increased concentration of testosterone in brain. This study may lead to ascertain a possible therapy in which sounds may be utilized to reduce anxiety in individual.

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... In other words, voluntary repetitive sound production and exposure lead to a recursive process. On one 3 hand, tubulin's sensitivity to sound waves influences the process. On the other hand, microtubules' ability to function as interferometers allows them to interpret the interactions between electromagnetic and sound waves. ...
... The study also reported an increase of human brain cell viability by approximately 20% following exposure to this frequency. In another study (Babayi Daylari et al. 2019), rats were exposed to 528 Hz and it was observed that this specific frequency increased brain testosterone production through mechanisms involving StAR and SF-1 gene expression, while reducing P450 aromatase activity. Additionally, exposure to 528 Hz led to a decrease of total reactive oxygen species (ROS) within brain tissue. ...
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... The study also reported an increase of human brain cell viability by approximately 20% following exposure to this frequency. In another study (Babayi Daylari et al. 2019), rats were exposed to 528 Hz and it was observed that this specific frequency increased brain testosterone production through mechanisms involving StAR and SF-1 gene expression, while reducing P450 aromatase activity. Additionally, exposure to 528 Hz led to a decrease of total reactive oxygen species (ROS) within brain tissue. ...
... Additionally, the identification of five solfeggio frequencies is intriguing. While the historical and musicological basis of solfeggio frequencies is debated, recent studies suggest potential benefits associated with these frequencies, including stress reduction and cognitive improvement (Babayi and Riazi 2017;Akimoto et al. 2018;Babayi Daylari et al. 2019;Dos Santos et al. 2023). These findings, if replicated with larger sample sizes, could contribute to the understanding of sound frequencies and their potential health impacts with particular reference to chanting Nam-Myoho-Renge-Kyo in the context of Nichiren Shoshu Liturgy. ...
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... These findings suggest that 528 Hz may mitigate ethanol-related cytotoxicity in astrocytes, warranting further in vivo and complex cellular model research. Daylari et al. (2018) investigated the impact of 528 Hz sound on anxiety-related behaviors in animal models. Rats exposed to daily 528 Hz for 2 hours over 21 days showed reduced anxiety behaviors compared to controls. ...
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To investigate some bioeffects of infrasound on copulation as well as underlying mechanisms, we inspected the changes of sexual behavior, serum testosterone concentration and mRNA expression levels of steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR) and cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) in testes of rats exposed to infrasound of 8Hz at 90 or 130dB for 1, 7, 14 and 21 days (2h/day), respectively. Rats exposed to 90dB exhibited significant decrement in sexual behavior, serum testosterone levels and mRNA expression levels of StAR and P450scc at the time point of 1 day but not at the rest time points, and no significantly change of SF-1 mRNA expression was observed over the period of 21 days in spite of mild fluctuation. Rats exposed to 130dB exhibited significant decrement in all aspects above, which became more profound with prolonged exposure. Our conclusion is that adverse bioeffects of infrasound on reproduction depend on some exposure parameters, the mechanism of which could involve in the decreased expression of some key enzymes or regulator for testosterone biosynthesis.
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The purpose of this study was to explore the efficacy of two music therapy protocols on pain, anxiety, and muscle tension levels during dressing changes in burn patients. Twenty-nine inpatients participated in this prospective, crossover randomized controlled trial. On two consecutive days, patients were randomized to receive music therapy services either on the first or second day of the study. On control days, they received no music. On music days, patients practiced music-based imagery (MBI), a form of music-assisted relaxation with patient-specific mental imagery before and after dressing changes. Also, on music days during dressing changes, the patients engaged in music alternate engagement (MAE), which consisted of active participation in music making. The dependent variables were the patients' subjective ratings of their pain and anxiety levels and the research nurse's objective ratings of their muscle tension levels. Two sets of data were collected before, three sets during, and another two sets after dressing changes. The results showed significant decrease in pain levels before (P < .025), during (P < .05), and after (P < .025) dressing changes on days the patients received music therapy in contrast to control days. Music therapy was also associated with a decrease in anxiety and muscle tension levels during the dressing changes (P < .05) followed by a reduction in muscle tension levels after dressing changes (P < .025). Music therapy significantly decreases the acute procedural pain, anxiety, and muscle tension levels associated with daily burn care.
Article
Although therapeutic ultrasound is commonly used to treat shoulder injuries, research to date on the ability of ultrasound to improve outcomes for shoulder pathologies is conflicting. This study aimed to systematically and critically review available literature to ascertain whether beneficial effects of ultrasound were associated with certain shoulder pathologies or particular ultrasound treatment protocols. Five electronic databases were searched, and the included studies, identified through pair consensus, were randomized controlled trials (RCTs) that utilized ultrasound for soft tissue shoulder injury or pain. Eight studies included in this review (n=586 patients, median PEDro score=8.0/10) evaluated various parameters, including the duration of patients' symptoms (0-12 months), duty cycle (20% and 100%), intensity (0.1-2.0 W/cm2), treatment time per session (4.5-15.8 minutes), number of treatments (6-39), and total energy applied per treatment (181-8,152 J). Inconsistent outcome measures among studies precluded meta-analysis; however, 3 RCTs showed statistically significant benefits of ultrasound, 2 of which examined calcific tendinitis. Studies that showed beneficial effects of ultrasound typically had 4 times longer total exposure times and applied much greater ultrasound energy per session (average of 4,228 J) compared with studies that showed no benefit of ultrasound (average of 2,019 J). No studies that delivered < or = 720 J per session showed improvement in treatment groups. Current research involving ultrasound treatment protocols that delivered low levels of ultrasound energy do not adequately address whether ultrasound can improve outcomes for shoulder disorders. Determining whether therapeutic ultrasound can affect soft tissue shoulder pathologies will require further research and systematic reviews that involve appropriate ultrasound treatment protocols.
Article
Molecular mechanisms contributing to the pathoetiology of hypertension are complex, involving many interacting systems such as signaling through G protein-coupled receptors, the renin-angiotensin system, vascular inflammation and remodeling, vascular senescence and aging and developmental programming, as highlighted in the current issue of the journal. Common to these systems is NADPH oxidase-derived reactive oxygen species (ROS). This editorial highlights current concepts relating to the production of ROS in hypertension and focuses on the Nox family NADPH oxidases, major sources of free radicals in the cardiovascular and renal systems. ROS play a major role as intracellular signaling molecules to regulate normal biological cellular responses. In pathological conditions, loss of redox homeostasis contributes to vascular oxidative damage. Recent evidence indicates that specific enzymes, the Nox family of NADPH oxidases, have the sole function of generating ROS in a highly regulated fashion in physiological conditions, and that in disease states, hyperactivation of Noxes contributes to oxidative stress and consequent cardiovascular and renal injury. The Nox family comprises seven members, Nox1-Nox7. Nox1, Nox2 (gp91phox-containing NADPH oxidase), Nox4 and Nox5 have been identified in the cardiovascular-renal systems and have been implicated in the pathophysiology of cardiovascular and renal disease. Noxes, which are differentially regulated in hypertension, are major sources of cardiovascular and renal oxidative stress. This has evoked considerable interest because of the possibilities that therapies targeted against specific Nox isoforms to decrease ROS generation or to increase nitric oxide availability or both may be useful in minimizing vascular injury and renal dysfunction, and thereby prevent or regress target organ damage associated with hypertension.
Article
The history of the tetrazolium salts and formazans goes back 100 years, to when Friese (1875) reacted benzene diazonium nitrate with nitromethane, to produce a cherry-red "Neue Verbindung". This was the first formazan. 19 years later, Von Pechmann and Runge (1894) oxidised a formazan to produce the first tetrazolium salt. Many hundreds of tetrazolium salts and formazans were prepared in the following years, but only a handful have found applications in biological research. This article has attempted to describe the properties of these compounds, and to illustrate how the tetrazolium salt-formazan reaction has been exploited to serve an extremely wide variety of functions.
Article
SF-1, a nuclear receptor that regulates gene expression of the cytochrome P450 steroid hydroxylases, and ELP, an embryonal protein that suppresses expression of the Moloney murine leukemia virus LTR, are isoforms transcribed from the same gene by alternative promoter usage and splicing. This gene is the mammalian homolog of the Drosophila fushi-tarazu factor 1 (FTZ-F1) gene. We have mapped the mouse gene Ftzf1 to the proximal quarter of Chr 2 by a linkage analysis using interspecific backcross mice, and its human homolog FTZ1 to Chr 9q33 by fluorescence in situ hybridization. The mouse and human genes are located in the homologous regions of mouse Chr 2 and human Chr 9, respectively.
Article
As an initial step toward understanding its role in steroidogenesis, we studied the developmental profile of steroidogenic factor-1 (SF-1), a nuclear receptor that regulates the steroid hydroxylases. SF-1 transcripts first appear on embryonic day 9 (E9) in the urogenital ridge, the probable source of steroidogenic cells of both adrenals and gonads. By E11, after the adrenals and gonads are clearly separate, SF-1 transcripts are detected throughout the adrenal primordium. Thereafter, adrenal expression of SF-1 localizes to the cortex. Consistent with its proposed role in regulating cholesterol side-chain cleavage enzyme (SCC), SF-1 is expressed before SCC. During the sexually undifferentiated stage of gonadal development (E9-E12), all embryos express SF-1 in the genital ridge. As testicular cords form in males, SF-1 transcripts are diffusely expressed throughout the testis, whereas SCC mRNA is limited to the interstitium. These differences between SF-1 and SCC reflect SF-1 expression by Sertoli cells, as shown by Northern blotting and in situ hybridization. In contrast to its persistent expression in the embryonic testis, SF-1 transcripts disappear from the ovary between E13.5-E16.5, reappearing only during late gestation (E18.5). Thus, expression of SF-1 in the embryonic gonad is sexually dimorphic. Coupled with the demonstration of SF-1 mRNA in Sertoli cells, these data suggest that SF-1 plays a role in gonadal development distinct from regulating the steroidogenic enzymes. Additionally, SF-1 is expressed in the embryonic forebrain, implying a role in neural development.
Article
Studies in adrenocortical cells have implicated the orphan nuclear receptor SF-1 in the gene regulation of the steroid hydroxylases. We used targeted disruption of the Ftz-F1 gene, which encodes SF-1, to examine its role in intact mice. Despite normal survival in utero, all Ftz-F1 null animals died by postnatal day 8; these animals lacked adrenal glands and gonads and were severely deficient in corticosterone, supporting adrenocortical insufficiency as the probable cause of death. Male and female Ftz-F1 null mice had female internal genitalia, despite complete gonadal agenesis. These studies establish that the Ftz-F1 gene is essential for sexual differentiation and formation of the primary steroidogenic tissues.
Article
Zinc deficiency is prevalent throughout the world, including the USA. Severe and moderate deficiency of zinc is associated with hypogonadism in men. However, the effect of marginal zinc deficiency on serum testosterone concentration is not known. We studied the relationship between cellular zinc concentrations and serum testosterone cross-sectionally in 40 normal men, 20 to 80 y of age. In four normal young men (27.5 +/- 0.5 y), we measured serum testosterone before and during marginal zinc deficiency induced by restricting dietary zinc intake. We also measured serum testosterone in nine elderly men (64 +/- 9 y) who were marginally zinc deficient before and after 3 to 6 mo of supplementation with 459 mumol/ d oral zinc administered as zinc gluconate. Serum testosterone concentrations were significantly correlated with cellular zinc concentrations in the cross-sectional study (lymphocyte zinc versus serum testosterone, r = 0.43, p = 0.006; granulocyte zinc versus serum testosterone, r = 0.30, p = 0.03). Dietary zinc restriction in normal young men was associated with a significant decrease in serum testosterone concentrations after 20 weeks of zinc restriction (baseline versus post-zinc restriction mean +/- SD, 39.9 +/- 7.1 versus 10.6 +/- 3.6 nmol/L, respectively; p = 0.005). Zinc supplementation of marginally zinc-deficient normal elderly men for six months resulted in an increase in serum testosterone from 8.3 +/- 6.3 to 16.0 +/- 4.4 nmol/L (p = 0.02). We conclude that zinc may play an important role in modulating serum testosterone levels in normal men.
Article
Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that serves as an essential regulator of many hormone-induced genes in the vertebrate endocrine system. The apparent absence of a SF-1 ligand prompted speculation that this receptor is regulated by alternative mechanisms involving signal transduction pathways. Here we show that maximal SF-1-mediated transcription and interaction with general nuclear receptor cofactors depends on phosphorylation of a single serine residue (Ser-203) located in a major activation domain (AF-1) of the protein. Moreover, phosphorylation-dependent SF-1 activation is likely mediated by the mitogen-activated protein kinase (MAPK) signaling pathway. We propose that this single modification of SF-1 and the subsequent recruitment of nuclear receptor cofactors couple extracellular signals to steroid and peptide hormone synthesis, thereby maintaining dynamic homeostatic responses in stress and reproduction.
Article
It is known that steroid hormones can affect neuronal susceptibility to different types of insults, including oxidative stress. Using an in vitro/ex vivo model, we have previously shown that cerebellar granule cells prepared from neonatal rats treated with a single dose of testosterone are less vulnerable to oxidative stress-induced cell death, via a mechanism involving an upregulation of the cellular antioxidant defenses. Whether the testosterone protective action on cerebellar granule cells was direct or indirect remained to be clarified. Therefore, in this study we have investigated the effects of in vitro testosterone treatment, to see whether it also protects cerebellar granule cells from oxidative stress-induced damage. Cerebellar granule cells treated with 10(-6) M testosterone for 48 h were found less susceptible to damage induced by 50 microM hydrogen peroxide, as shown by a 30% decrease in the number of cells with apoptotic morphology. The addition of the androgen receptor antagonist flutamide abolished the protective effect of testosterone, suggesting an androgen receptor-mediated mechanism. This hypothesis was further supported by the presence of the androgen receptor in cultured cerebellar granule cells. The activity of the antioxidant enzyme catalase was also measured, and a 2-fold increase was detected in the testosterone treated cells, but not in the cells co-treated with flutamide. The present results demonstrate that cerebellar granule cells treated in vitro with testosterone are protected from oxidative stress via a mechanism mediated by the androgen receptor. Similarly to what we observed after in vivo administration of testosterone, the potentiation of the antioxidant defences seems to play a major role in the protection afforded by testosterone.
Article
At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish "redox homeostasis." Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical-mediated oxidative damage was proposed more than 40 years ago by Harman (J Gerontol 11: 298-300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
Article
The biological activity of testosterone and dihydrotestosterone is thought to occur predominantly through binding to the androgen receptor (AR), a member of the nuclear receptor superfamily that functions as a ligand-activated transcription factor. However, androgens have also been reported to induce the rapid activation of kinase-signaling cascades and modulate intracellular calcium levels. These effects are considered to be nongenomic because they occur in cell types that lack a functional AR, in the presence of inhibitors of transcription and translation, or are observed to occur too rapidly to involve changes in gene transcription. Such nongenomic effects of androgens may occur through AR functioning in the cytoplasm to induce the MAPK signal cascade. In addition, androgens may function through the sex hormone binding globulin receptor and possibly a distinct G protein-coupled receptor to activate second messenger signaling mechanisms. The physiological effect of nongenomic androgen action has yet to be determined. However, it may ultimately contribute to regulation of transcription factor activity, including mediation of the transcriptional activity of AR.
Article
Recent studies have suggested that testosterone levels are lower in men with Alzheimer's disease and that testosterone treatment improves cognition in older men. Since testosterone can be aromatized to estrogen, testosterone's effects could be due to conversion into estrogen. We treated aged male rats with either testosterone or dihydrotestosterone (DHT), the latter of which is not aromatized to estrogen, in order to determine whether these treatments improve spatial working and reference memory as assessed in the water radial arm maze. We also tested whether such effects are related to beta-amyloid levels in the hippocampus or neurotrophin levels in the hippocampus, entorhinal cortex, frontal cortex, or striatum. Aged rats made more errors than young rats on all memory measures. Testosterone, but not DHT, improved working memory and decreased hippocampal NGF protein in aged rats, while having no effect on beta-amyloid. However, higher beta-amyloid levels were correlated with poorer working memory performance in young rats. Neurotrophin levels in entorhinal cortex were positively correlated with errors for all memory measures in androgen-treated rats. Similar to findings in human studies, in our study androgen treatment lowered circulating estradiol levels in aged rats, suggesting that androgen treatment exerts feedback to the hypothalamic pituitary axis and that conversion to estrogen may not be the underlying biological mechanism of testosterone's effects on memory and growth factor levels. The ratio of estradiol to testosterone, or the actions of the aromatase enzyme itself, may be responsible for the observed effects. These data support the hypothesis that testosterone therapy in aging men may provide positive effects on cognition and that neural regions that are linked to cognition, such as the hippocampus and/or entorhinal cortex, may be involved in such effects.
Article
An investigation has been made of the points of coupling between four tetrazolium salts and the respiratory chain (succinate to O2) in rat-liver tissue suspensions. Each tetrazolium salt has been studied with four levels of tissue and under various incubation conditions. The effects of various respiratory-chain inhibitors on these reactions have been studied in order to localise where the tetrazolium salts are reacting with the respiratory chain. The reaction of nitro-blue tetrazolium with the respiratory chain is virtually insensitive to the presence of antimycin A, or to the level of O2 in the incubation mixture. This and other evidence suggests that nitro-blue tetrazolium reacts almost completely at one site on the respiratory chain, possibly ubiquinone. C,N-diphenyl-N′-4,5-dimethylthiazol-2-yltetrazolium bromide, however, appears to react at two sites of roughly equal importance, one of which is sensitive to antimycin A; this latter site is in the region of cytochrome c. Of the other two tetrazolium salts investigated here, triphenyltetrazolium chloride reacts with the terminal oxidase, and 2-p-nitrophenyl-3-p-iodophenyl-5-phenyltetrazolium chloride reacts in a manner similar to C,N-diphenyl-N′-4,5-dimethylthiazol-2-yltetrazolium bromide. These results, combined with the results for neotetrazolium chloride in the preceding communication, are discussed in terms of previous reports in the literature and the applicability of using tetrazolium reduction for histochemical purposes.
Article
Estradiol plays a key role in the control of many behavioral and physiological aspects of reproduction therefore the expression of cytochrome P450 aromatase (CYP19), the enzyme responsible for the conversion of androgens to estrogens, is of vital interest. The zebrafish, and many other teleosts, have two aromatase genes (CYP19A1 and CYP19A2) that are expressed predominantly in the ovary and brain, respectively, however, the physiological impact of extra-gonadal aromatase has been poorly described. In this study, in situ hybridizations of whole-mount and paraffin sections of adult zebrafish brains, pituitaries, and ovarian follicles showed that CYP19A2 was strongly expressed in the olfactory bulb (OB), ventral telencephalon (TEL), preoptic area (POA), and ventral/caudal hypothalamic zone (HT) of the brain, and in the anterior and posterior lobes of the pituitary. The regional distribution of the CYP19A2 mRNA did not vary with sex however transcript abundance varied within (male "high expressers" had much higher expression in the OB, TEL, and HT than in "low expressers") and between sexes (higher in OB, TEL, and HT of males than in females). In situ hybridizations of CYP19A1 failed to develop a signal in the brain or pituitary but were detectable by RT-PCR. CYP19A1 was highly expressed in Stage III B follicles (>500 nm) with significantly lower levels in the Stage IV follicles (>680 nm), Stage III A follicles (>350 nm), and Stage I and II follicles (350 microm) which were embedded in connective tissues. The differential expression of the aromatase genes, particularly CYP19A2 in the brain, suggests that the two aromatase genes play different roles in the reproductive behavior and/or physiology of bony fish.
Article
Nongenomic androgen actions imply mechanisms different from the classical intracellular androgen receptor (iAR) activation. We have recently reported the identification of a membrane androgen receptor (mAR) on LNCaP human prostate cancer cells, mediating testosterone signal transduction within minutes. In the present study we provide evidence that activation of mAR by nonpermeable, BSA-coupled testosterone results in 1) inhibition of LNCaP cell growth (with a 50% inhibitory concentration of 5.08 nM, similar to the affinity of testosterone for membrane sites); 2) induction in LNCaP cells of both apoptosis and the proapoptotic Fas protein; and 3) a significant decrease in migration, adhesion, and invasion of iAR-negative DU145 human prostate cancer cells. These actions persisted in the presence of antiandrogen flutamide or after decreasing the content of iAR in LNCaP cells by iAR antisense oligonucleotides. Testosterone-BSA was also effective in inducing apoptosis of DU145 human prostate cancer cells, negative for iAR, but expressing mAR sites. In LNCaP cell-inoculated nude mice, treatment with testosterone-BSA (4.8 mg/kg body weight) for 1 month resulted in a 60% reduction of tumor size compared with that in control animals receiving only BSA, an effect that was not affected by the antiandrogen flutamide. Our findings suggest that activators of mAR may represent a new class of antitumoral agents of prostate cancer.
Healing codes for the biological apocalypse
  • L G Horowitz
  • LG Horowitz
Horowitz LG (2000) Healing codes for the biological apocalypse. Tetrahedron Publishing Group, Sandpoint, pp 251-253
System and method for treating pets. United States patent US 9
  • R Levi
  • G Martinovsky
  • G Neuman
Levi R, Martinovsky G, Neuman G(2015) System and method for treating pets. United States patent US 9,107,389. 2015