Organically produced coffee exerts protective effects against the micronuclei induction by mutagens in mouse gut and bone marrow

While researchers have extensively evaluated the beneficial effects of coffee consumption in reducing the frequency of certain diseases, studies examining the differences between organic and conventional coffee intake are still needed. Therefore, this paper aims to investigate the functional effects of organic and conventional coffee by examining both its chemical composition and its mutagenic/antimutagenic properties. Infusions of 10% or 20% (w/v) of organic and conventional coffee were administered by gavage (10 mL/kg b.w., once or twice a day) to male Swiss mice against doxorubicin (DXR) and 1,2-dimethylhydrazine dihydrochloride (DMH)-induced mutagenicity. The levels of chlorogenic acids, caffeine and trigonelline from the coffee infusions and oxidative stress analysis from the liver were measured by HPLC. Gut and bone marrow micronucleus assays were used as mutagenic/antimutagenic endpoints, as well as the crypt measurements and gut apoptosis index. The in vivo tests revealed that only organic coffee exerted protective effects, despite oxidative stress analysis and crypt measurements not showing differences among treatments. Intriguingly, the low dose (10% w/v mL/kg) displayed a robust protective effect that showed a significant reduction in bone marrow micronuclei (26.8%), gut micronuclei (11.5%) and apoptosis (27.8%), whereas the higher coffee dose (2 × 20% w/v) only showed a protective effect against bone marrow micronucleus (43.7%). These results highlight that organic coffee could be considered to have beneficial functional effects, although it is still a challenge to define conclusions from analytical data and all the possible interactions from this complex food matrix. © 2013 Elsevier Ltd. All rights reserved.

EPA protects against muscle damage in the mdx mouse model of Duchenne muscular dystrophy by promoting a shift from the M1 to M2 macrophage phenotype

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação do perfil de expressão gênica de células CD34+ e células CD CD133+ isoladas de medula óssea e de sangue de cordão umbilical

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37) on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 µm ("thin" or "thick" dendrites, respectively). Three cells (4.5%) were bistratified, having thick dendrites, and the others (95.5%) were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40%) and 2 groups with inner (50-100%) stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

Protective role of melatonin in mouse spermatogenesis induced by sodium arsenite

Arsenic is a testicular environmental toxic. Melatonin (Me), being a potent antioxidant, may reduce the damage caused by arsenic in male fertility. The effects of daily oral exposure of Sodium Arsenite (As; 7.0 mg/kg/bw); Melatonin (Me, 10.0 mg/kg/bw); Me (10.0 mg/kg/bw) plus As (7.0 mg/kg/bw), and Negative Control (NaCl 0.9%) in male CF-1 adult mice were assessed in acute (8.3 days), chronic (33.2 days) and recovery (66,4 days) of testicular damage. We evaluated changes in testicular weight and histopathological, morphometric measurements, expression of COX-2 and Androgen Receptor (AR) antigens and lipid peroxidation levels. Treatment resulted in decreased tubular diameter and AR expression, and increased: interstitial area, luminal diameter, COX-2 expression levels and of lipid peroxidation. Co-administration of As and Me partially decreased germ cell degeneration and AR expression levels, improving testicular histopathological parameters. These results indicate that As causes toxicity and testicular germ cell degeneration by induction of oxidative stress. Me partially protects from this damage in mouse testis, acting as scavenger of oxygen radical species.

Melatonin Protective Role in Mouse Cauda Epipidymal Spermatozoa Damage Induced by Sodium Arsenite

We evaluated the sperm parameters such as cauda epididymis weight, sperm count, sperm morphology and sperm DNA stability of adult CF-1 male mice treated daily (oral exposure) with the toxic sodium arsenite (As, 7.0 mg/kg/body weight); Melatonin (Me, 10.0 mg/kg/bw), Me (10.0 mg/kg/bw) plus As (7.0 mg/kg/bw) and Negative Control (NaCl 0.9%) to assess acute (8.3 days), chronic (33.2 days) and recovery of testicular damage (66.4 days). Arsenic decreases the number of sperm from chronic treatment (33.2 days) and this effect continued until 66.4 days of treatment. The toxic effect of As also altered the morphology of spermatozoa in all treatment periods when compared to the negative control group. However, Metalonin induced protective effects in periods of 33.2 and 66.4 days of treatment. Additionally, the stability of DNA was significantly affected by arsenic in all periods, but the chronic treatment (33.2 days) in the AsMe revealed increased stability compared to the group treated with arsenic only. Melatonin partially protects sperm toxicity caused by Arsenic, especially during periods of 33.2 and 66.4 days.

IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma

Background: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

M-CSF Priming of Osteoclast Precursors Can Cause Osteoclastogenesis-Insensitivity, Which Can be Prevented and Overcome on Bone

Osteoclasts and macrophages share progenitors that must receive decisive lineage signals driving them into their respective differentiation routes. Macrophage colony stimulation factor M-CSF is a common factor; bone is likely the stimulus for osteoclast differentiation. To elucidate the effect of both, shared mouse bone marrow precursor myeloid blast was pre-cultured with M-CSF on plastic and on bone. M-CSF priming prior to stimulation with M-CSF and osteoclast differentiation factor RANKL resulted in a complete loss of osteoclastogenic potential without bone. Such M-CSF primed cells expressed the receptor RANK, but lacked the crucial osteoclastogenic transcription factor NFATc1. This coincided with a steeply decreased expression of osteoclast genes TRACP and DC-STAMP, but an increased expression of the macrophage markers F4/80 and CD11b. Compellingly, M-CSF priming on bone accelerated the osteoclastogenic potential: M-CSF primed cells that had received only one day M-CSF and RANKL and were grown on bone already expressed an array of genes that are associated with osteoclast differentiation and these cells differentiated into osteoclasts within 2 days. Osteoclastogenesis-insensitive precursors grown in the absence of bone regained their osteoclastogenic potential when transferred to bone. This implies that adhesion to bone dictates the fate of osteoclast precursors. Common macrophage-osteoclast precursors may become insensitive to differentiate into osteoclasts and regain osteoclastogenesis when bound to bone or when in the vicinity of bone. J. Cell. Physiol. 229: 210-225, 2014. (c) 2014 Wiley Periodicals, Inc.

Spontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: A novel ONJ mouse model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Classificação morfológica e imunostoquímica em microarranjo de tecido (TMA) de linfomas não-Hodgkin em cães conforme os critérios da Histological Classification od Hematopoietic Tumors of Domestic Animals (WHO)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A method using artificial neural networks to morphologically assess mouse blastocyst quality

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Oral changes in individuals undergoing hematopoietic stem cell transplantation

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression. OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation. METHODS: A prospective study was carried out with 65 patients aged > 18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients); B (autologous transplant, 31 patients). A total of three dental status assessments were performed: in the pre-transplantation period (moment 1), one week after stem cell infusion (moment 2), and 100 days after transplantation (moment 3). In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks. RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression. CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications.