Ent-kaurenoic acid-enriched Mikania glomerata leaves-complexed ß-cyclodextrin: Pharmaceutical development and in vivo antitumor activity in a sarcoma 180 mouse model.

The extract obtained from Mikania glomerata leaves rich in ent-kaurenoic acid (ERKA) shows cytotoxic activity in vitro, but its hydrophobic nature and thermosensitivity are issues to be solved prior to in vivo antitumor studies. The purpose of this study was to investigate the antitumor activity of inclusion complexes formed between ERKA and ß-cyclodextrin (ERKA:ß-CD) in rodents. ERKA:ß-CD complexes obtained by malaxation (MX) and co-evaporation (CE) methods were firstly characterized regarding their physical properties, encapsulation efficiency, and cytotoxicity againts L929 cells. The antitumor activity study was then performed in mice with sarcoma 180 treated with saline, 5-fluouracil (5FU) and ERKA:ß-CD at 30, 100 and 300 µg/kg. The weight, volume, percentage of inhibition growth, gross and pathological features and positivity for TUNEL, ki67, NFκB and NRF2 in the tumors were assessed. Serum lactate-dehydrogenase activity (LDH), white blood cells count (WBC) and both gross and pathological features of the liver, kidneys and spleen were also evaluated. The formation of the inclusion complexes was confirmed by thermal analysis and FTIR, and they were non-toxic for L929 cells. The MX provided a better complexation efficiency. ERKA:ß-CD300 promoted significant tumor growth inhibition, and attenuated the tumor mitotic activity and necrosis content, comparable to 5-fluorouracil. ERKA:ß-CD300 also increased TUNEL-detected cell death, reduced Ki67 and NF-kB immunoexpression, and partially inhibited the serum LDH activity. No side effect was observed in ERKA:ß-CD300-treated animals. The ERKA:ß-CD inclusion complexes at 300 µg/kg displays antitumour activity in mice with low systemic toxicity, likely due to inhibition on the NF-kB signaling pathway and LDH activity.

Differentiated Immunohistochemical Expression of Osteoclastogenic Markers in Radicular Cyst, Odontogenic Keratocyst, and Ameloblastoma.

The aim of this study was to investigate the osteoclastogenesis process by means of immunohistochemical markers for receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), interleukin-6 (IL-6), and cathepsin K (CTSK) antigens in osteolytic lesions of maxillary bones. The sample consisted of 23 radicular cysts (RC), 25 odontogenic keratocysts (OKC), and 25 ameloblastomas (AM). RANKL was statistically higher in RC (49.6±15.2/53.7±18) and OKC (48.6±15.1/51.4±16.8) when compared with AM (37.2±12.5/36.4±13) in the epithelium and connective tissue. OPG was lower in OKC (34.8±18.5) only in connective tissue when compared with RC (44.5±11.2). The expression of RANKL was statistically higher than OPG in RC (epithelium and connective tissue) and OKC (connective tissue). For IL-6, a statistical difference was observed only in the connective tissue between groups, with higher expression in RC (48.2±15) and lower in OKC (22±11.9). The expression of IL-6 was correlated with the intensity of the inflammatory infiltrate. CTSK was statistically higher in AM (34±19) and OKC (29±13.8) compared with RC (19±10.5). According to the results of the present research the bone resorption in cysts and odontogenic tumors occurs through different mechanisms. The ostoclastogenic process in lesions with aggressive clinical behavior, as AM and OKC, seems to be associated with the expression of CTSK. In contrast, lesions with inflammatory etiology, as RC, the expression of IL-6 seems to have an important role in the bone resorption process. The highest expression of RANKL under the expression of OPG also seems to contribute to the growth mechanism of RC and OKC.

Contribution of Endemic Listeriosis to Spontaneous Abortion and Stillbirth in a Large Outdoor-housed Colony of Rhesus Macaques (Macaca mulatta).

Listeria monocytogenes is an endemic agent in the primate population at the California National Primate Research Center and has been associated with both sporadic cases and a general outbreak of pregnancy failures. The primary objective of this study was to verify the incidence of L. monocytogenes-associated abortion and fetal deaths in the Center's outdoor breeding colony. In addition, we sought to compare the group of female macaques that presented with Listeria-associated abortion with both those with nonlisteria-associated abortion and animals with successful pregnancy outcome. We calculated the incidence of L. monocytogenes-associated abortion and stillbirth by dividing the number of positive L. monocytogenes cultures from aborted fetuses by the number of pregnant female macaques from 1989 through 2009. To compare the pregnancy outcome of female macaques that have presented L. monocytogenes-associated abortion and stillbirth, we created 2 control groups: female macaques with successful pregnancy outcomes during the 1999 breeding season and animals with nonlisteria-associated pregnancy failure. These macaques were followed for 2 subsequent breeding seasons. The results showed a range in the incidence of L. monocytogenes-associated abortion and stillbirth from 0% to 8.39% throughout the 1989 to 2009 breeding seasons. In addition, the Listeria-associated abortion group did not present statistically significant differences in fertility and abortion rates when compared with the control groups. We conclude that although L. monocytogenes is an endemic agent at the Center's outdoor breeding colony, the agent's incidence varied in significance. Furthermore, an episode of L. monocytogenes-associated abortion did not affect subsequent pregnancies.

Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: relation to opportunistic infections.

AIMS: To quantify and compare the expression of Langerhans cells (LCs) in the tongue mucosa of AIDS patients with different opportunistic infections, and from acquired immune deficiency syndrome (AIDS) and non-AIDS patients with normal tongues, using autopsy material. METHODS AND RESULTS: Human leucocyte antigen D-related (HLA-DR), CD1a and CD83 antibodies were used to identify and quantify LCs by immunohistochemistry in tongue tissue of 40 AIDS patients (10 with lingual candidiasis, 10 with lingual herpes, 10 with oral hairy leukoplakia and 10 with no lesions) and 23 tongues from human immunodeficiency virus (HIV)-negative control patients. Quantification was performed by means of conventional morphometry in four different regions (anterior, middle, posterior and lateral) of the tongue. The results were expressed as positive cells per area of epithelium. The AIDS patients presented a lower density of CD1a(+) cells (P < 0.001), HLA-DR (P < 0.003) and CD83 (P < 0.001) in all regions of the tongue compared to the non-AIDS control group. However, no differences in any of the markers were found when AIDS patients with different opportunistic infections were compared with AIDS patients without tongue infection. CONCLUSIONS: Advanced stage AIDS patients showed a depletion of LCs in the tongue mucosa. HIV infection induces cytopathic changes in LCs, contributing to their depletion regardless of the presence of oral infections.

Myositis ossificans traumatica of the medial pterygoid muscle: a case report.

In this report, we present a case of myositis ossificans traumatica (MOT) of the medial pterygoid muscle that had developed after mandibular block anesthesia administered for endodontic treatment of the lower right second molar, demonstrating typical features of this condition. MOT should be considered as a differential diagnosis when there is severe limitation of jaw opening and an associated trauma. Panoramic radiographs and axial and coronal computed tomography (CT) scans can effectively delineate the calcified mass. Other imaging studies that may be helpful include magnetic resonance imaging (MRI), bone scans, and ultrasound. As shown in our case, calcified masses were found in the right mandibular angle, which severely limited jaw opening. Some earlier reported cases of MOT were treated by extraoral surgical approaches with complete removal of the evolving muscle. The aim of this case report is to present only the diagnostic imaging aspects of myositis ossificans traumatica.