Primary cutaneous mucormycosis (zygomycosis) caused by Apophysomyces elegans

A 53 year-old male diabetic presented with a month-old, painful ulcer with necrotic margins over the right thigh. Wound debridement was done twice and the ulcer showed recurrent growth of a white, cottony filamentous structure. Cutaneous mucormycosis was suspected and confirmed by histopathology and a culture isolate of Apophysomyces elegans . The patient was treated with liposomal amphotericin-B and itraconazole followed by partial thickness skin grafting, and then discharged after being prescribed posaconazole syrup for three weeks. Regular follow-up was done and during the last visit after six months following discharge, the ulcer was found to have healed well with no recurrence of the fungus.     

Consumption of Stearidonic Acid−Rich Oil in Foods Increases Red Blood Cell Eicosapentaenoic Acid

BackgroundConsumption of soybean oil enriched with stearidonic acid was previously shown to increase eicosapentaenoic acid (EPA) in red blood cells (RBC).ObjectiveThis study was designed to evaluate the effect of stearidonic acid oil used as a food ingredient in baked products and beverages on the RBC fatty acid profile.DesignThis was a randomized, double-blind, controlled, parallel-arm study.ParticipantsHealthy men and women 21 to 65 years of age were included.InterventionParticipants consumed either negative control (1.5 g/day high-oleic sunflower ethyl ester oil softgel capsules+foods containing 7 g/day high-oleic sunflower oil), positive control (1.5 g/day EPA oil ethyl ester softgel capsules+foods containing 7 g/day high-oleic sunflower oil), or active (1.5 g/day high-oleic sunflower ethyl ester oil softgel capsules+foods containing 7 g/day stearidonic acid soybean oil) for 12 weeks.Main outcome measuresRBC membrane fatty acid profile (at weeks 0, 2, 4, 6, 8, 10, and 12); fasting serum lipids (weeks ?2, 0, 6, 10, and 12); and fasting plasma glucose and insulin (weeks ?2, 0, 10, and 12) were assessed.Statistical analyses performedA repeated measures analysis of covariance was used for continuous variables, and pair-wise comparisons between treatments were adjusted using a step-down Bonferroni method. Fisher’s exact or χ² tests were used for categorical data.ResultsRBC %EPA throughout the 12-week study were significantly different between all groups. Means at 12 weeks were 0.50%±0.03%, 2.17%±0.21%, and 0.85%±0.05% for control, EPA, and stearidonic acid, respectively. Other efficacy outcome measures were not significantly different among treatment groups.ConclusionsConsumption of stearidonic acid-enriched soybean oil incorporated into common foods increased RBC %EPA in healthy men and women. Stearidonic acid soybean oil, a sustainable and accessible source of long-chain n-3, can effectively be used to increase EPA in RBC.     

Therapeutic significance of estrogen receptor β agonists in gliomas

Gliomas are the most common and devastating central nervous system neoplasms. A gender bias exists in their development: females are at lower risk than males, implicating estrogen-mediated protective effects. Estrogen functions are mediated by two estrogen receptor (ER) subtypes: ERα, which functions as tumor promoter, and ERβ, which functions as tumor suppressor. We examined the potential use of ERβ agonists as a novel therapeutic to curb the growth of gliomas. Western analysis of six glioma model cells showed detectable expression of ERβ with little or no ERα. Treatment of glioma cells with ERβ agonists resulted in significant decrease in proliferation. Immunohistochemical analysis of tumor tissues revealed that ERβ expression is downregulated in high-grade gliomas. We found that ERβ agonists promote both expression and tumor-suppressive functions of ERβ in glioma cells. Liquiritigenin, a plant-derived ERβ agonist significantly reduced in vivo tumor growth in a xenograft model. Compared with control mice, animals treated with liquiritigenin had greater than 50% reduction in tumor volume and size. Immunohistochemical analysis of tumors revealed a significant increase in the nuclear ERβ expression with a concomitant decrease in cell proliferation in the liquiritigenin-treated group. Our results suggest that ERβ signaling has a tumor-suppressive function in gliomas. Because ERβ agonists are currently in clinical trials and are well tolerated with fewer side effects, identification of an ERβ agonist as a therapeutic agent can be readily extended to clinical use with current chemotherapies, providing an additional tool for enhancing survival in glioma patients.     

miRNA-29b suppresses prostate cancer metastasis by regulating epithelial-mesenchymal transition signaling

Prostate cancer remains the second leading cause of cancer deaths among American men. Early diagnosis increases survival rate in patients; however, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment are necessary for inhibiting prostate cancer disease progression. Here, we have shown that miRNA-29b (miR-29b) expression was lower in prostate cancer cells (PC3 and LNCaP) as compared with immortalized prostate epithelial cells. Between these two prostate cancer cell lines, metastatic prostate cancer PC3 cells displayed lower expression of miR-29b. We also observed a significant downregulation of miR-29b expression in human prostate cancer tissues as compared with patient-matched nontumor tissues. PC3 cells ectopically expressing miR-29b inhibited wound healing, invasiveness, and failed to colonize in the lungs and liver of severe combined immunodeficient mice after intravenous injection, while PC3 cells expressing a control miRNA displayed metastasis. Epithelial cell marker E-cadherin expression was enhanced miR-29b transfected in prostate cancer cells as compared with cells expressing control miRNA. On the other hand, N-cadherin, Twist, and Snail expression was downregulated in PC3 cells expressing miR-29b. Together these results suggested that miR-29b acts as an antimetastatic miRNA for prostate cancer cells at multiple steps in a metastatic cascade. Therefore, miR-29b could be a potentially new attractive target for therapeutic intervention in prostate cancer.     

H5D12 Monoclonal Antibody Identifies a 24-kD Immunosuppressor Factor Produced by Human Chorio Carcinoma Cells

PROBLEM: The purpose of this study was to identify and characterize embryo-associated immunosuppressor factor (EASF) secreted by chorio carcinoma cells with the help of EASF-specific monoclonal antibody H5D12 (raised against EASF purified from embryo growth media of in vitro fertilized human ova). METHOD: Paraffin-embedded slides of human chorio carcinoma as well as control cell lines were prepared, and immunohistochemistry was done by the avidin-biotin-peroxidase technique. EASF was affinity purified using H5D12-Sepharose 4B from culture media of cell lines and analyzed for immunosuppressive activity (by Concanavalin-A-induced lymphocyte proliferation assay) and molecular weight identity (by metabolic-labelling studies with ³⁵S-methionine followed by immunoprecipitation and SDS-PAGE). RESULTS: H5D12 showed intense immunostaining of BeWo chorio carcinoma cells. Bio-synthetic labeling studies identifies this factor as a 24-kD molecule, and EASF bioassay indicates that this factor possesses immunosuppressive activity. No such immunosuppressive activity or similar molecules were identified when control cell lines were analyzed. CONCLUSIONS: Monoclonal antibody H5D12 recognizes a 24-kD factor with immunosuppressive activity that is secreted by chorio carcinoma cells, which suggests that this is a unique factor and may be one of the key regulators of reproductive functions.     

Ultrastructural changes in the principal cells of epididymis of adult rhesus monkey (Macaca mulatta) after castration and androgen replacement therapy

The epididymal epithelium from adult castrated and androgen supplemented, castrated rhesus monkeys was examined with transmission electron microscope. Ninety days after bilateral castration the tubular diameter of all the regions of the epididymis, viz. the initial segment, caput, corpus and cauda portions of epididymis was reduced and was accompanied by a drop in cell size. There was a marked decrease in the number and size of microvilli on the luminal surface. The invaginations of apical membrane into the cell cytoplasm became less prominent. There was a reduction in the amount of smooth and rough endoplasmic reticulum, and Golgi complex. Mitochondria accumulated in the apical cytoplasm. Several vacuoles often associated with lipofuscin pigment granules were common in the cytoplasm. These findings suggest a reduction in both the absorptive and secretory functions of the principal cells. Following androgen replacement therapy for 30 days in monkeys that were castrated 60 days earlier there was a recovery of structural features in the epithelium to near normal state.     

Polyamine effects uponN-methyl-D-aspartate receptor functioning: differential alteration by glutamate and glycine site antagonists

Polyamines such as spermidine potentiate activation of theN-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. The goal of the present study was to investigate interactions between the putative polyamine binding site and previously described sites for glutamate and glycine. Binding of the high-potency PCP receptor ligand [³H]MK-801 to well-washed rat brain membranes was used as an in vitro probe of NMDA receptor activation. Spermidine concentration-response studies were performed in the absence and presence of both glutamate and glycine, with and withoutD-(−)-2-amino-5-phosphonovaleric acid (D(−)AP-5) or 7-chlorokynurenic acid (7Cl-KYN). Incubation in the presence of spermidine alone induced a 20.4-fold increase in [³H]MK-801 binding with an EC₅₀ value of 13.3 μM. The mean concentration of spermidine which induced maximal stimulation of binding was 130 μM (n = 10,S.E.M.= 24.66,range= 25–250 μM). Glutamate (10 μM) decreased the EC₅₀ value for spermidine-induced stimulation of [³H]MK-801 binding to 3.4 μM. Glycine (10 μM) did not significantly alter either maximum spermidine-induced [³H]MK-801 binding or the EC₅₀ value for spermidine-induced stimulation of [³H]MK-801 binding. Incubation in the presence of the specific glutamate antagonistD(−)AP-5 attenuated [³H]MK-801 binding in a glutamate-reversible fashion. The competitive glycine antagonist 7Cl-KYN decreased maximum spermidine-induced [³H]MK-801 binding in a glycine-reversible fashion. In addition, 7Cl-KYN increased the EC₅₀ value for spermidine-induced stimulation of [³H]MK-801 binding whileD(−)AP-5 was without effect. These findings suggest that glutamate and glycine regulate the polyamine binding site differentially. PCP-like agents induce a psychotomimetic state closely resembling schizophrenia by inhibiting NMDA receptor-mediated neurotransmission. The ability of polyamines to modulate NMDA receptor functioning suggests a potential site for pharmacological intervention.