Malignant fibrous histiocytoma of the glans penis: a case report

BACKGROUND: Malignant fibrous histiocytoma has been regarded as the most common sarcoma of older adults. However, recent opinion regards pleomorphic malignant fibrous histiocytoma as an undifferentiated high grade pleomorphic sarcoma not otherwise classifiable utilizing current techniques available in surgical pathology. Notwithstanding controversy regarding its nomenclature, malignant fibrous histiocytoma involving the penis is exceedingly rare, with only 4 cases previously described, to our knowledge. CASE: An uncircumcised 73-year-old male presented with a painless, granular, partially necrotic lesion beneath the penile foreskin. There was no history of sexually transmitted disease, constitutional symptoms or dysuria. Examination of penile shaft, testicles, spermatic cord and inguinal lymph nodes were unremarkable. Biopsy revealed a markedly pleomorphic sarcoma. Subsequent, partial penectomy revealed the same lesion with an adjacent area of squamous cell carcinoma in situ. CONCLUSION: Malignant fibrous histiocytoma remains a diagnosis of exclusion. The investigation requires extensive tumor sampling in search of areas of differentiation and a complete battery of immunohistochemical markers. Therapeutically important entities in the differential diagnosis that must be ruled out include other poorly differentiated sarcomas, sarcomatoid squamous cell carcinoma and desmoplastic melanoma.     

Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats

Weight regain after weight loss is the most significant impediment to long-term weight reduction. We have developed a rodent paradigm that models the process of regain after weight loss, and we have employed both prospective and cross-sectional analyses to characterize the compensatory adaptations to weight reduction that may contribute to the propensity to regain lost weight. Obese rats were fed an energy-restricted (50-60% kcal) low-fat diet that reduced body weight by 14%. This reduced weight was maintained for up to 16 wk with limited provisions of the low-fat diet. Intake restriction was then removed, and the rats were followed for 56 days as they relapsed to the obese state. Prolonged weight reduction was accompanied by 1) a persistent energy gap resulting from an increased drive to eat and a reduced expenditure of energy, 2) a higher caloric efficiency of regain that may be linked with suppressed lipid utilization early in the relapse process, 3) preferential lipid accumulation in adipose tissue accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that underestimate the level of peripheral adiposity and likely influence the neural pathways controlling energy balance. Taken together, long-term weight reduction in this rodent paradigm is accompanied by a number of interrelated compensatory adjustments in the periphery that work together to promote rapid and efficient weight regain. These metabolic adjustments to weight reduction are discussed in the context of a homeostatic feedback system that controls body weight.     

Critical conditions for ferric chloride-induced flocculation of freshwater algae

The effects of algae concentration, ferric chloride dose, and pH on the flocculation efficiency of the freshwater algae Chlorella zofingiensis can be understood by considering the nature of the electrostatic charges on the algae and precipitate surfaces. Two critical conditions are identified which, when met, result in flocculation efficiencies in excess of 90% for freshwater algae. First, a minimum concentration of ferric chloride is required to overcome the electrostatic stabilization of the algae and promote bridging of algae cells by hydroxide precipitates. At low algae concentrations, the minimum amount of ferric chloride required increases linearly with algae concentration, characteristic of flocculation primarily through electrostatic bridging by hydroxide precipitates. At higher algae concentrations, the minimum required concentration of ferric chloride for flocculation is independent of algae concentration, suggesting a change in the primary flocculation mechanism from bridging to sweep flocculation. Second, the algae must have a negative surface charge. Experiments and surface complexation modeling show that the surface charge of C. zofingiensis is negative above a pH of 4.0 ± 0.3 which agrees well with the minimum pH required for effective flocculation. These critical flocculation criteria can be extended to other freshwater algae to design effective flocculation systems.     

Effects of housing density on nasal pathology of breeding mice housed in individually ventilated cages

The 2011 edition of the Guide for the Care and Use of Laboratory Animals includes new recommendations for the amount of floor space that should be provided to breeding mice. When pairs or trios of continuously breeding mice are housed in shoebox cages, they may have less than this recommended amount of floor space. High housing densities may adversely affect animal health, for example, by compromising air quality inside the cage. Hence, some institutions are carefully reevaluating the microenvironments of breeding cages. The use of individually ventilated cages (IVCs) to house research mice allows for greater control over the quality of the cage microenvironment. The authors evaluated the microenvironments of shoebox cages in an IVC rack system housing breeding and non-breeding Swiss Webster mice. Ammonia concentrations were significantly higher in cages housing breeding trios with two litters. Histopathologic lesions attributable to inhaled irritants such as ammonia were found in mice housed in breeding pairs and trios. The authors conclude that the microenvironments of cages in an IVC rack system housing breeding pairs and trios may be detrimental to animal health.     

Production of an Extracellular Matrix as an Isotropic Growth Phase of Penicillium rubens on Gypsum

Indoor mold represents an important environmental concern, but a fundamental knowledge of fungal growth stages is needed to limit indoor fungal proliferation on finishing materials used in buildings. The present study focused on the succession of germination stages of the common indoor fungus Penicillium rubens on a gypsum substrate. This substrate is used as a model system representing porous materials that are widely used in indoor environments. Imaging with cryo-scanning electron microscopy showed that the formation of an extracellular matrix (ECM) is a phase of the isotropic growth of P. rubens that is uniquely related to germinating conidia. Furthermore, the ECM is observed only when a dry-state inoculation of the surface is applied, i.e., applying conidia directly from a 7-day-old colony, mimicking airborne contamination of the surface. When inoculation is done by spraying an aqueous conidial suspension, no ECM is observed. Moreover, it is concluded that the formation of an ECM requires active processes in the fungal cell. The porosity of the substrate proved that the ECM substance has high-viscosity characteristics. The present results stress that studies of indoor fungal growth should consider the method of inoculation, knowing that the common aqueous suspension may obscure specific stages in the initial phases of germination.     

Interspecies pair housing of macaques in a research facility

The eighth edition of The Guide for the Care and Use of Laboratory Animals establishes social housing as the 'default' for social species including non-human primates. The advantages of social housing for primates have been well established, but small research facilities housing few primates in indoor cages have struggled with social housing as a result of limitations on appropriate housing and availability of compatible monkeys. Here, we report a novel approach to pair housing macaques - crossing species. We have successfully pair housed an intact male rhesus macaque with an intact male cynomolgus macaque, and an adult female rhesus macaque with numerous subadult female cynomolgus macaques. Monkeys in these pairs established dominant-subordinate relationships similar to same-species pairs. Rhesus and cynomolgus macaques can be successfully paired for the purpose of social housing in facilities with limited numbers of monkeys.     

Relationship between treatment preference and weight loss in the context of a randomized controlled trial

Randomized controlled trials (RCTs) are considered the gold standard used to assess the efficacy of treatment. While a well implemented RCT can produce an unbiased estimate of the relative difference between treatment groups, the generalizability of these findings may be limited. Specific threats to the external validity include treatment preference. The purposes of this study were to: (i) assess whether receiving one's treatment preference was associated with weight loss and retention and (ii) whether receiving one's treatment preference modified the relationship between the treatments and weight loss. Treatment preference was assessed in 250 subjects prior to but independent of randomization into either low-carbohydrate or low-fat diets. Treatment preference was a predictor of weight loss (P = 0.002) but not retention (P = 0.90). Participants who received their preference lost less weight (-7.7 kg, 95% confidence interval (CI): -9.3 to -6.1) than participants who did not receive their preference (-9.7 kg, 95% CI: -11.4 to -8.1) and participants who did not report a strong preference at baseline (-11.2 kg, 95% CI: -12.6 to -9.7) (P = 0.04 and P = 0.0004, respectively). Treatment preference did not modify the effect of the treatment on weight loss. Contrary to conceptual predictions, this study failed to identify an interaction between treatment preference and weight loss in the setting of a randomized trial. Until treatment preference effects are definitively ruled out in this domain, future studies might consider stratifying their randomization procedure by treatment preference rather than excluding participants with strong treatment preferences.     

Morphological Changes in the Midgut of Aedes aegypti L. (Diptera: Culicidae) Larvae Following Exposure to an Annona coriacea (Magnoliales: Annonaceae) Extract

Bioinsecticides are important in the control of disease vectors, but data regarding their physiological effects on target insects are incomplete. This study describes morphological changes that occur in the midgut of third instar Aedes aegypti L. (Diptera: Culicidae) following treatment with a methanolic extract of Annona coriacea (Magnoliales: Annonaceae). Dissected midguts were subdivided into anterior and posterior regions and analyzed by light and scanning electron microscopy. Insects exposed to the extract displayed intense, destructive cytoplasmic vacuolization in columnar and regenerative midgut cells. The apical surfaces of columnar cells exhibited cytoplasmic protrusions oriented toward the lumen, suggesting that these cells could be involved in apocrine secretory processes and/or apoptosis. We report that A. coriacea extracts induced morphological alterations in the midgut of A. aegypti midgut larvae, supporting the use of plant extracts for control of the dengue vector.     

Anti-neoplastic activity of two flavone isomers derived from Gnaphalium elegans and Achyrocline bogotensis

Over 4000 flavonoids have been identified so far and among these, many are known to have antitumor activities. The basis of the relationships between chemical structures, type and position of substituent groups and the effects these compounds exert specifically on cancer cells are not completely elucidated. Here we report the differential cytotoxic effects of two flavone isomers on human cancer cells from breast (MCF7, SK-BR-3), colon (Caco-2, HCT116), pancreas (MIA PaCa, Panc 28), and prostate (PC3, LNCaP) that vary in differentiation status and tumorigenic potential. These flavones are derived from plants of the family Asteraceae, genera Gnaphalium and Achyrocline reputed to have anti-cancer properties. Our studies indicate that 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone) displays potent activity against more differentiated carcinomas of the colon (Caco-2), and pancreas (Panc28), whereas 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone) cytototoxic action is observed on poorly differentiated carcinomas of the colon (HCT116), pancreas (Mia PaCa), and breast (SK-BR3). Both flavones induced cell death (>50%) as proven by MTT cell viability assay in these cancer cell lines, all of which are regarded as highly tumorigenic. At the concentrations studied (5-80 μM), neither flavone demonstrated activity against the less tumorigenic cell lines, breast cancer MCF-7 cells, androgen-responsive LNCaP human prostate cancer line, and androgen-unresponsive PC3 prostate cancer cells. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone) displays activity against more differentiated carcinomas of the colon and pancreas, but minimal cytotoxicity on poorly differentiated carcinomas of these organs. On the contrary, 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone) is highly cytotoxic to poorly differentiated carcinomas of the colon, pancreas, and breast with minimal activity against more differentiated carcinomas of the same organs. These differential effects suggest activation of distinct apoptotic pathways. In conclusion, the specific chemical properties of these two flavone isomers dictate mechanistic properties which may be relevant when evaluating biological responses to flavones.