Testosterone Nanoemulsion Prevents Prostate Cancer: PC-3 and LNCaP Cell Viability In Vitro.

For many years, it has been speculated that elevated testosterone levels may be critically involved in the genesis and proliferation of prostate cancer. METHODS: The effect of testosterone on the metabolic activity of hormone-independent [PC-3] and hormone-dependent [LNCAP] cancer cells was investigated in vitro. Additionally, the impact of testosterone nanoemulsion [nanocare®] on cell viability was accessed by flow cytometry. RESULTS: Despite the dependency of the normal prostate and of most prostatic cancers upon androgens, the obtained results indicate that, contrary to prevailing opinion, the supplementation of testosterone with higher doses in nanoemulsion was able to lower the metabolic activity and viability of prostate cancer cells. CONCLUSIONS: We conclude that the growth of hormone-independent and hormone-dependent prostate cancer cells was reduced by the exposure of a nanoemulsion of bioidentical testostosterone in vitro. To the best of our knowledge, this is the first time that the potential effect of a testosterone nanoemulsion on the metabolic activity of prostate cancer cells has been shown. Such tests suggest that the growth of hormone-independent and hormone-dependent prostate cancer cells was reduced by the administration of bioidentical testostosterone, and this might be an interesting strategy for prostate cancer treatment in diagnosed patients.

Vaginal probiotics on the outcomes of premature rupture of membranes: a pilot randomised clinical trial.

The published literature shows that a balanced vaginal microbiota can have a favourable impact on decreasing the prevalence of premature rupture of membranes (PROM). We studied the effects of vaginal probiotics (Lactobacillus rhamnosus and L. gasseri) on the outcomes of PROM in pregnant women between 24 and 36 weeks of gestation. We performed a randomised, triple-blind, placebo-controlled study. A total of 27 participants were divided into two groups-group 1 (probiotics; n = 16) and group 2 (placebo; n = 11). Although most outcomes did not show much variation, the latency period and gestational age at delivery were higher in group 1 than in group 2. Thus, vaginal use of L. rhamnosus and L. gasseri along with standard treatment appears to increase the latency period and gestational age at delivery in women with PROM.IMPACT STATEMENTWhat is already known on this subject? Delaying delivery increases the risk of infections, but the prolongation of pregnancy allows further foetal maturation, thus reducing the risk of complications associated with premature birth. Moreover, a more extended latency period in pregnancies of <37 weeks of gestation is associated with a better neonatal prognosis.What do the results of this study add? The use of probiotics (L. rhamnosus and L. gasseri) prolongs the latency period in pregnant women with premature rupture of membranes.What are the implications of these findings for clinical practice and/or further research? Probiotics are an exciting option for extending the time to delivery in cases of premature rupture of the membrane, allowing the maturation of the foetal lung.

The effect of bioidentical nanostructured progesterone in the in vitro culture of preantral follicles and oocyte maturation.

This study evaluated the effects of bioidentical nanostructured progesterone alone or in association with human chorionic gonadotropin (hCG) on the in vitro survival and development of preantral follicles (experiment 1) and oocyte maturation (experiment 2). Bioidentical hormones have a molecular structure identical with that of endogenous hormones; nanostructured substances refer to those reduced to a nanoscale. In experiment 1, fragments of goat ovarian tissue were cultured for 7 days in α-MEM+ alone or supplemented with nanoprogesterone (MEM+ + P4) or P4 and hCG (MEM+ + P4 + hCG). In experiment 2, two mediums of oocyte in vitro maturation (IVM) were compared. Medium 1 consisted of TCM 199+ + LH, and medium 2 consisted of TCM 199+ with nanoprogesterone and hCG. The MEM+ + P4 + hCG treatment showed the lowest percentage of follicular survival after 7 days of culture. MEM+ + P4 and MEM+ + P4 + hCG treatments showed higher percentage of follicular activation than MEM+. In experiment 2, there were no differences between mediums 1 and 2 for all endpoints evaluated. In conclusion, the addition of nanoprogesterone is advisable for in vitro culture of preantral follicles and oocyte maturation. However, the association of nanoprogesterone with hCG causes the cellular death of initial follicles but shows efficacy in IVM.

Supplementation with Herbal Extracts to Promote Behavioral and Neuroprotective Effects in Experimental Models of Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti-apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.

3,6-Dimethoxy-6″,6″-Dimethyl-(7,8,2″,3″)-Chromeneflavone, a Flavonoid Isolated from Lonchocarpus Araripensis Benth. (Fabaceae), Reduces Nociceptive Behaviour in Mice.

Lonchocarpus araripensis Benth. is largely distributed in the northeast region of Brazil. It is popularly known as 'sucupira'. Recent studies have shown that some species of Lonchocarpus have interesting pharmacological activities. In this study, we evaluated the antinociceptive effect of a flavone isolated from L. araripensis. The chemical examination resulted in the isolation of 3,6-dimethoxy-6″,6″-dimethyl-(7,8,2″,3″)-chromeneflavone (DDF). The structure of the compound was established by spectral analysis. Antinociceptive activity of DDF was evaluated by measuring nociception by acetic acid, formalin and hot plate tests. The rota rod test was used to evaluate motor coordination. The results demonstrated that DDF was able to prevent acetic-acid-writhing-induced nociception (p < 0.001) in mice. Furthermore, DDF produced a significant reduction of the nociceptive behaviour at the early and late phases of paw licking in the formalin test. Also, DDF produced an inhibition of the nociceptive behaviour during a hot-plate test. No alteration in motor coordination was observed. These results confirm the hypothesis that DDF reduces the nociceptive behaviour in mice, probably through central mechanisms, but without compromising the motor coordination of animals.

Comparative effect of an essential oil mouthrinse on plaque, gingivitis and salivary Streptococcus mutans levels: a double blind randomized study.

An open, randomized, controlled study with two parallel treatment groups was done to evaluate the efficacy of a Lippia sidoides essential oil (EO) 1% mouthrinse compared with chlorhexidine 0.12% mouthrinse, applied two times daily for 1 week, in the treatment of dental plaque and gingivitis. Fifty-five patients were included in the study. The efficacy variables were the colony count of Streptococcus mutans from the stimulated saliva and periodontal indices on days 0, 7 and 30 after commencement of therapy. Twenty eight patients received chlorhexidine mouthrinse (Periogard((R))) and 27 Lippia sidoides essential oil mouthrinse (Cepakill((R))). The clinical and microbiological parameters were significantly reduced by both mouthrinses. No significant difference was seen between the two groups (p > 0.05). There was a significant reduction in the colony count of S. mutans in both groups (p < 0.05). Chlorhexidine treatment reduced more efficiently than L. sidoides, however, no statistical difference was seen, the efficacy of both groups was similar (p = 0.3). The results indicate that Chlorhexidine mouthrinse reduced plaque index, gingival bleeding and the number of CFU (colonies forming units) more efficiently than L. sidoides but did not reach statistical significance. This study demonstrated that Lippia sidoides EO mouthrinse is effective in reducing microbial plaque and gingival inflammation.

Photoprotective potential of medicinal plants from Cerrado biome (Brazil) in relation to phenolic content and antioxidant activity.

Photooxidative damage affects cellular lipids, proteins and DNA in addition to being involved in the pathobiochemistry of erythema formation, premature skin aging, photodermatoses development and skin cancer. Phenolic compounds, flavonoids and hydroxycinnamic acid esters protect plant tissues against harmful UV-radiation. This study aimed to evaluate the sun protection factor of several Brazilian plant extracts in relation to UVB radiation absorption, which causes skin cancer, and to correlate the findings with their antioxidant activity, as well as with total phenol and flavonoid content. The antioxidant activity of the extracts were evaluated using the DPPH radical scavenging test. The photoprotective effect was evaluated using the methodology developed by Mansur. The antioxidant activity from the extracts showed IC50 values ranging from 4.91 to 132.24 µg/mL when compared to the standard quercetin with an IC50 of 5.01 µg/mL; the phenolic content varied from 3.77 to 57.14 mg GAE/g extract while flavonoid content varied from 1.80 to 5.89 mg EQ/g extract. Almost all extracts showed a potential for UVB radiation absorption in accordance with the ANVISA (Agência Nacional de Vigilância Sanitária) technical regulation for cosmetic sunscreens. The extracts with greater sun protection factors were those originating from Lippia microphylla (SPF = 26.82) and Dimorphandra gardneriana (SPF = 20.12). A sun protection factor of 15 or higher contributes to protect the skin, where the presence of sakuranetin flavonoids and quercetin glycosides contribute to this action.

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study.

OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women.

Expansion and phenotypic changes of mouse bone marrow mesenchymal cells cultured with FGF-2 and facial nerve-conditioned medium / Expansión y cambios fenotípicos de células mesenquimales de médula ósea de ratón cultivadas con FGF-2 y medio condicionado por el nervio facial

Mesenchymal cells (MCs) exhibit great regenerative potential due to their intrinsic properties and ability to restore tissue function, either directly through transdifferentiation or indirectly through paracrine effects. This study aimed to evaluate morphometric and phenotypic changes in MCs grown with facial nerve-conditioned medium in the presence or absence of fibroblast growth factor 2 (FGF-2). For quantitative phenotypic analysis, the expression of GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200 was analyzed by immunocytochemistry. Cells cultured with facial nerve-conditioned medium in the presence of FGF-2 expressed GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200. On average, the area and perimeter of GFAP-positive cells were higher in the group cultured with facial nerve-conditioned medium compared to the group cultured with conditioned medium and FGF-2 (p=0.0001). This study demonstrated the plasticity of MCs for neuronal and glial lineages and opens up new research perspectives in cell therapy and trans.differentiation.

Las células mesenquimales (CM) exhiben un gran potencial regenerativo debido a sus propiedades intrínsecas y la capacidad de restaurar la función del tejido, ya sea directamente, a través de la transdiferenciación, o indirectamente, a través de efectos parácrinos. Este estudio tuvo como objetivo evaluar los cambios morfométricos y fenotípicos en CM cultivadas con medio condicionado por nervio facial en presencia o ausencia de factor de crecimiento de fibroblastos 2 (FGF-2). Para el análisis fenotípico cuantitativo, se analizó la expresión de GFAP, OX-42, MAP-2, β-tubulina III, NeuN y NF-200 mediante inmunocitoquímica. Las células cultivadas con medio condicionado por el nervio facial en presencia de FGF-2 expresaban GFAP, OX-42, MAP-2, β-tubulina III, NeuN y NF-200. En promedio, el área y el perímetro de las células positivas para GFAP fueron mayores en el grupo cultivado con medio condicionado por el nervio facial en comparación con el grupo cultivado con medio acondicionado y FGF-2 (p = 0,0001). Este estudio demostró la plasticidad de CM para linajes neuronales y gliales y abre nuevas perspectivas de investigación en terapia celular y transdiferenciación.

Nanotechnology in ligature-induced periodontitis: protective effect of a doxycycline gel with nanoparticules.

OBJECTIVES: The aim of this study was to test the efficacy of a locally applied 8.5% nanostructured doxycycline (DOX) gel in preventing alveolar bone loss in experimental periodontal disease (EPD) in rats by using the tapping mode atomic force microscopy (AFM). MATERIAL AND METHODS: EPD was induced in 24 Wistar rats. Animals were treated with the doxycycline gel topically, immediately after EPD induction, and 3 times a day during 11 days. Four groups (n=6) were formed as follows: Naïve group (animals not subjected to EPD nor treated); non-treated (NT) group (animals subjected to EPD, but not treated); vehicle gel (VG) group (animals subjected to EPD and treated with topical gel vehicle); and DOX group (test group): animals subjected to EPD and treated with the 8.5% DOX gel. In order to investigate topographical changes in histological sections, a novel simple method was used for sample preparation, by etching sections from paraffin-embedded specimens with xylol. RESULTS: Comparing the AFM images, several grooves were observed on the surface of the alveolar bone and other periodontal structures in the NT and VG groups, with significantly greater depths when compared to the DOX group (p<0.05). CONCLUSIONS: Periodontal structures were brought into high relief confirming to be a simple and cost-effective method for AFM imaging with ultrastructural resolution. The doxycycline gel was able to afford periodontal surface preservation, with flatter grooves.

Effects of a transdermal testosterone metered-dose nanoemulsion in peri- and postmenopausal women: a novel protocol for treating low libido / Efeitos de nanoemulsãom transdérmica dosimetrada de testosterona em mulheres peri-e pós-menopausa: um novo protocolo para o tratamento de libido reduzido

OBJECTIVE: To investigate the efficacy of a transdermal nanoemulsion testosterone associated with transdermal estrogen therapy as a novel protocol treatment for emergent loss of libido. METHODS: Twenty-four women, aged 31-75 years (mean age, 51.7), with emergent loss of libido were allocated to treatment with a novel transdermal formulation of 500 µg/day of testosterone (Biolipid/B2®-testosterone) for 12 weeks, as part of an open label prospective study on peri- and post-menopausal women. Subjects applied the formulation on the right forearm. Clinical and laboratorial parameters including the sexual complaints; serum concentrations of testosterone, insulin, C-reactive protein, weight, blood pressure; body mass index and waist circumference were compared between baseline and 12 weeks after treatment. RESULTS: The mean total serum testosterone increased significantly (p = 0.009) after 12 weeks of treatment. No adverse or androgenic events were observed. There were positive and significant differences (p < 0.05) on sexual complaints, blood pressure, body mass index and waist circumference after transdermal nanoemulsion testosterone treatment. CONCLUSION: This protocol is effective in increasing testosterone levels in peri- and postmenopausal women with low libido.

OBJETIVO: Investigar a eficácia de uma nanoemulsão transdérmica de testosterona associada à terapia com estrogênio transdérmico como tratamento para a perda emergente da libido. MÉTODOS: Vinte e quatro mulheres, com idade entre 31-75 anos (idade média de 51,7), com perda emergente de libido foram incluídas num protocolo para tratamento de libido reduzida com uma formulação transdérmica de 500 µg/dia de testosterona (biolípido/B2®-testosterona) com 12 semanas de duração, como parte de um estudo prospectivo aberto em mulheres peri- e pós-menopausa. As participantes aplicaram a formulação no antebraço direito. Os parâmetros clínicos e laboratoriais, incluindo as queixas sexuais foram comparados entre os valores iniciais e 12 semanas após o tratamento. Mediram-se as concentrações séricas de testosterona, insulina, proteína C-reactiva, o peso, a pressão arterial; o índice de massa corporal e a circunferência da cintura. RESULTADOS: A média de testosterona total no soro aumentou significativamente (p = 0,009) após 12 semanas de tratamento. Não foram observados efeitos adversos ou androgênicos. Registraram-se reduções significativas (p < 0,05) sobre as queixas sexuais, da pressão arterial, do índice de massa corporal e da circunferência da cintura após o tratamento transdérmico com nanoemulsão de testosterona. CONCLUSÃO: O protocolo mostrou eficacia em aumentar os níveis de testosterona em e melhorar a libido em mulheres peri e pós-menopausa com baixa libido.

Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. .

Phythochemical screening and antimicrobial activity phythochemical of essential oil from Lippia gracillis

The chemical composition of the essential oil obtained from the fresh and dried leaves of Lippia gracillis Schauer, Verbenaceae, was analyzed by gas chromatography and gas chromatography/mass spectrometry (GC⁄MS). The yield of essential oil extracted from the dried leaves was significantly higher (p<0.05) when compared to the fresh leaves. Seventeen components were identified. The monoterpenes and sesquiterpene hydrocarbons with 96.26 percent (w/w) of the total oil obtained of fresh leaves and 86.99 percent (w/w) of the total oil obtained of dried leaves were the principal compound groups. Thymol was observed dominant (44.42 percent; 21.3 percent), followed by carvacrol (22.21 percent; 21.30 percent), p-cymene (6.23 percent; 8.58 percent), α-pinene (5.65 percent; 19.42 percent), β-caryophyllene (5.61 percent; 3.57 percent) and other minor constitutes, respectively. Microbiological results obtained by agar diffusion method, micro dilution method and minimum inhibitory concentration (MIC) showed that the essential oil has a relevant antimicrobial activity against E. coli (ATCC 10536), E. coli (Ec 27), Pseudomonas aeruginosa (ATCC 15442), S. aureus (ATCC 12692) and S. aureus (Sa 358), with their inhibition zones ranging from 9 to 13 mm and the MIC ranging from 64 to 512 μg/mL.

Nanotechnology in ligature-induced periodontitis: protective effect of a doxycycline gel with nanoparticules

OBJECTIVES: The aim of this study was to test the efficacy of a locally applied 8.5 percent nanostructured doxycycline (DOX) gel in preventing alveolar bone loss in experimental periodontal disease (EPD) in rats by using the tapping mode atomic force microscopy (AFM). MATERIAL AND METHODS: EPD was induced in 24 Wistar rats. Animals were treated with the doxycycline gel topically, immediately after EPD induction, and 3 times a day during 11 days. Four groups (n=6) were formed as follows: Naïve group (animals not subjected to EPD nor treated); non-treated (NT) group (animals subjected to EPD, but not treated); vehicle gel (VG) group (animals subjected to EPD and treated with topical gel vehicle); and DOX group (test group): animals subjected to EPD and treated with the 8.5 percent DOX gel. In order to investigate topographical changes in histological sections, a novel simple method was used for sample preparation, by etching sections from paraffin-embedded specimens with xylol. RESULTS: Comparing the AFM images, several grooves were observed on the surface of the alveolar bone and other periodontal structures in the NT and VG groups, with significantly greater depths when compared to the DOX group (p<0.05). CONCLUSIONS: Periodontal structures were brought into high relief confirming to be a simple and cost-effective method for AFM imaging with ultrastructural resolution. The doxycycline gel was able to afford periodontal surface preservation, with flatter grooves.