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1.
J Med Primatol ; 51(6): 381-383, 2022 12.
Article in English | MEDLINE | ID: mdl-35394073

ABSTRACT

Primary female reproductive neoplasms in Platyrrhines species are few reported. We present the gross, histological, and immunohistochemical findings of metastatic endometrioid carcinoma in the uterus, urinary bladder, jejunum, and rectum of a Leontopithecus sp. The neoplastic endometrial cells expressed strong cytoplasmic immunolabeling of cytokeratin 7.


Subject(s)
Carcinoma, Endometrioid , Endometrial Neoplasms , Leontopithecus , Animals , Female , Carcinoma, Endometrioid/veterinary , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/secondary , Endometrial Neoplasms/pathology , Endometrial Neoplasms/veterinary , Immunohistochemistry/veterinary , Uterus/pathology
2.
Reprod Toxicol ; 81: 147-154, 2018 10.
Article in English | MEDLINE | ID: mdl-30086341

ABSTRACT

Throughout the last decades, increasing exposure to environmental Endocrine Disruptors Chemicals (EDCs) has been associated with the occurrence of male reproductive disorders, such as impairment of prostate development and function, increase of susceptibility to oncogenesis, Epithelial-Mesenchymal Transition and the metastatic invasive potential. Nevertheless, few studies address the mechanisms involved in these alterations, especially those related to cell junctions, which are hormonally regulated and, therefore, possible EDCs targets. The cellular mechanisms discussed in this review are addressed to EDCs actions on tight, gap and adherent junctions and its related genes and proteins, such as claudin-1, -3, -4 and -8, connexin-32 and -43, E-cadherin and ß-catenin, respectively. The impairment of cell junction function, mainly due EDCs exposure during the prostate's critical window of development, can corroborate to acquire a mesenchymal phenotype by epithelial cells and the prostate microenvironment becomes susceptible to development of lesions in the latter stages of life.


Subject(s)
Endocrine Disruptors/toxicity , Intercellular Junctions/drug effects , Prostate/drug effects , Animals , Epithelial-Mesenchymal Transition/drug effects , Humans , Male , Prostate/growth & development , Prostatitis/chemically induced , Xenobiotics/toxicity
3.
J Pharmacol Toxicol Methods ; 94(Pt 1): 14-18, 2018.
Article in English | MEDLINE | ID: mdl-29630936

ABSTRACT

INTRODUCTION: Vaginal route is often used in topical antifungal formulations. Vaginal permeability assays are generally performed as in vitro tests. METHOD: An in vivo vaginal permeability assay was developed using female rabbits. Fenticonazole permeability was evaluated by assessing fenticonazole bioavailability in plasma by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS). Toxicity was monitored histopathologically after 8 consecutive days of antifungal treatment (20 mg/animal). RESULTS: The method of quantification was linear with a lower limit of quantification (LLOQ) of (0.1 ng/mL). The area-under-the-curves (AUC) of fenticonazole on day 1 and 8 of treatment were 280.3 ±â€¯86.1 ng/mL ∗ h and 805.7 ±â€¯252.4 ng/mL ∗ h, respectively. The calculated systemic bioavailability was 12.73% ±â€¯0.14%. No signs of toxicity were observed both macroscopically and histologically after 8 days fenticonazole treatment. DISCUSSION: The plasma levels of fenticonazole observed in rabbits are similar to that observed in human. Rabbit vagina may be a suitable model to evaluate vaginal antifungal formulations.


Subject(s)
Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Imidazoles/administration & dosage , Imidazoles/adverse effects , Vagina/metabolism , Administration, Intravaginal , Animals , Antifungal Agents/blood , Area Under Curve , Biological Availability , Chromatography, Liquid/methods , Female , Imidazoles/blood , Permeability , Rabbits , Tandem Mass Spectrometry/methods
4.
PLoS One ; 8(6): e66903, 2013.
Article in English | MEDLINE | ID: mdl-23840551

ABSTRACT

Most amniotes vertebrates have an intromittent organ to deliver semen. The reptile Sphenodon and most birds lost the ancestral penis and developed a cloaca-cloaca mating. Known as hemipenises, the copulatory organ of Squamata shows unique features between the amniotes intromittent organ. They are the only paired intromittent organs across amniotes and are fully inverted and encapsulated in the tail when not in use. The histology and ultrastructure of the hemipenes of Crotalus durissus rattlesnake is described as the evolutionary implications of the main features discussed. The organization of hemipenis of Crotalus durissus terrificus in two concentric corpora cavernosa is similar to other Squamata but differ markedly from the organization of the penis found in crocodilians, testudinata, birds and mammals. Based on the available data, the penis of the ancestral amniotes was made of connective tissue and the incorporation of smooth muscle in the framework of the sinusoids occurred independently in mammals and Crotalus durissus. The propulsor action of the muscle retractor penis basalis was confirmed and therefore the named should be changed to musculus hemipenis propulsor.The retractor penis magnus found in Squamata has no homology to the retractor penis of mammals, although both are responsible for the retraction of the copulatory organ.


Subject(s)
Crotalus/anatomy & histology , Evolution, Molecular , Animals , Male
5.
Am J Physiol Lung Cell Mol Physiol ; 304(10): L639-45, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23475769

ABSTRACT

Bone marrow (BM) eosinopoiesis is a common feature during allergen exposure in atopic individuals. Airway exposure to staphylococcal superantigens aggravates allergic airway disease and increases the output of BM eosinophils. However, the exact mechanisms regulating eosinophil mobilization and trafficking to the peripheral circulation and airways remain to be elucidated. Therefore, this study aimed to investigate the mechanisms determining the BM eosinopoiesis in allergic mice under exposure to staphylococcal enterotoxin A (SEA). Ovalbumin (OVA)-sensitized male BALB/C mice were intranasally exposed to SEA (1 µg), and at 4, 12, 24, and 48 h later animals were challenged with OVA (10 µg, twice a day). Measurement of IL-5, eotaxin, and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels, flow cytometry for CCR3(+), VLA4(+), and CCR3(+)VLA4(+), as well as adhesion assays to VCAM-1 were performed in BM. Prior airway exposure to SEA time dependently increased the BM eosinophil number in OVA-challenged mice. Eosinophils gradually disappear from peripheral blood, being recruited over time to the airways, where they achieve a maximal infiltration at 24 h. SEA exposure increased the levels of IL-5 and eotaxin (but not GM-CSF) in BM of OVA-challenged mice. Marked increases in CCR3(+) and CCR3(+)VLA4(+) expressions in BM eosinophils of OVA-challenged mice were observed, an effect largely reduced by prior exposure to SEA. Adhesion of BM eosinophils to VCAM-1 was increased in OVA-challenged mice, but prior SEA exposure abrogated this enhanced cell adhesion. Accumulation of BM eosinophils by airway SEA exposure takes place through IL-5- and CCR3-dependent mechanisms, along with downregulation of CCR3/VL4 and impaired cell adhesion to VCAM-1.


Subject(s)
Allergens/immunology , Bone Marrow/immunology , Cell Movement/immunology , Enterotoxins/immunology , Eosinophilia/immunology , Respiratory System/immunology , Allergens/metabolism , Animals , Bone Marrow/metabolism , Bone Marrow/pathology , Eosinophilia/metabolism , Eosinophilia/pathology , Eosinophils/immunology , Eosinophils/metabolism , Eosinophils/pathology , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Integrin alpha4beta1/immunology , Integrin alpha4beta1/metabolism , Interleukin-5/immunology , Interleukin-5/metabolism , Male , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Receptors, CCR3/immunology , Receptors, CCR3/metabolism , Respiratory System/metabolism , Respiratory System/pathology , Vascular Cell Adhesion Molecule-1/immunology , Vascular Cell Adhesion Molecule-1/metabolism
6.
J Sex Med ; 8(6): 1616-25, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21477017

ABSTRACT

INTRODUCTION: Coitus in snakes may last up to 28 hours; however, the mechanisms involved are unknown. AIM: To evaluate the relevance of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) system in snake corpus cavernosum reactivity. METHODS: Hemipenes were removed from anesthetized South American rattlesnakes (Crotalus durissus terrificus) and studied by light and scanning electronic microscopy. Isolated Crotalus corpora cavernosa (CCC) were dissected from the non-spiny region of the hemipenises, and tissue reactivity was assessed in organ baths. MAIN OUTCOME MEASURES: Cumulative concentration-response curves were constructed for acetylcholine (ACh), sodium nitroprusside (SNP), 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272), and tadalafil in CCC precontracted with phenylephrine. Relaxation induced by electrical field stimulation (EFS) was also done in the absence and presence of N(ω) nitro-L-arginine methyl ester (L-NAME; 100 µM), 1H-[1, 2, 4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 µM) and tetrodotoxin (TTX; 1 µM). RESULTS: The hemipenes consisted of two functionally concentric corpora cavernosa, one of them containing radiating bundles of smooth muscle fibers (confirmed by α-actin immunostaining). Endothelial and neural nitric oxide synthases were present in the endothelium and neural structures, respectively; whereas soluble guanylate cyclase and PDE5 were expressed in trabecular smooth muscle. ACh and SNP relaxed isolated CCC, with the relaxations being markedly reduced by L-NAME and ODQ, respectively. BAY 41-2272 and tadalafil caused sustained relaxations with potency (pEC(50) ) values of 5.84 ± 0.17 and 5.10 ± 0.08 (N=3-4), respectively. In precontracted CCC, EFS caused frequency-dependent relaxations that lasted three times longer than those in mammalian CC. Although these relaxations were almost abolished by either L-NAME or ODQ, they were unaffected by TTX. In contrast, EFS-induced relaxations in marmoset CC were abolished by TTX. CONCLUSIONS: Rattlesnake CC relaxation is mediated by the NO-cGMP-PDE5 pathway in a manner similar to mammals. The novel TTX-resistant Na channel identified here may be responsible for the slow response of smooth muscle following nerve stimulation and could explain the extraordinary duration of snake coitus.


Subject(s)
Cyclic GMP/metabolism , Nitrergic Neurons/drug effects , Nitric Oxide Synthase/metabolism , Penis/blood supply , Penis/innervation , Sodium Channel Blockers/pharmacology , Sodium Channels/drug effects , Sodium Channels/physiology , Tetrodotoxin/pharmacology , Acetylcholine/pharmacology , Animals , Callithrix , Carbolines/pharmacology , Crotalus , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , Dose-Response Relationship, Drug , Endothelium, Vascular/anatomy & histology , Endothelium, Vascular/drug effects , In Vitro Techniques , Male , Microscopy, Electron, Scanning , NG-Nitroarginine Methyl Ester/pharmacology , Nitroprusside/pharmacology , Oxadiazoles/pharmacology , Penis/anatomy & histology , Pyrazoles/pharmacology , Pyridines/pharmacology , Quinoxalines/pharmacology , Tadalafil , Vasodilator Agents/pharmacology
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