Fine structure of the 7 postnatal days Calomys callosus palatine salivary glands.

The aim of this study has been to determine the ultrastructural characteristics of the minor palatine salivary glands on the seventh day of development and to demonstrate wether their secretion is mucous, serous or seromucous by light, transmission and scanning electron microscopy. This study has shown that the palatine gland acinar cells are predominantly mucous with some serous units. These cells contain electron dense (serous) and low electron dense (mucous) granules in the apical portions. The cytoplasmatic organelles like mitochondria, Golgi apparatus and rough endoplasmic reticulum are localized in a supranuclear portion. We could also observe the flattened myoepithelial cells surrounding the basal part of the acini with myofilaments, Golgi apparatus and mitochondria. Desmosomal junctions and membrane interdigitations are present between the acinar and the myoepithelial cells. A basal lamina, divided in two layers, an electron dense and an electron lucent is present between the glandular stroma which is composed of dense connective tissue and the endpieces.     

Hyaline cell-rich chondroid syringoma: case report and review of the literature

Hyaline cell-rich chondroid syringoma (HCRCS) is a rare benign cutaneous neoplasm composed of cells with eosinophilic hyaline cytoplasm and plasmacytoid features, the origin of which remains elusive. To the best of our knowledge, only eight cases of this entity have been reported so far, and none of them was submitted to a large panel of myoepithelial markers. We report on a case of a previously healthy 29-year-old male patient who presented with a slowly enlarging flesh-colored nodule on the palmar aspect of the tenar region of his left hand, measuring 2 cm in maximum diameter. The nodule was "shelled-out" and submitted to light microscopy, immunohistochemistry, and ultrastructural examination. Histopathologic analysis disclosed a lobulated neoplasm composed of hyaline cells with plasmacytoid features showing ovoid nuclei, with occasional invaginations, finely granular chromatin, and discrete nucleoli; the cytoplasm was deeply eosinophilic with occasional dot-shaped paranuclear hyaline inclusions. On immunohistochemical evaluation, hyaline cells were strongly and diffusely positive for S-100 protein, vimentin, pan (CAM 5.2) and high molecular weight (34betaE12) cytokeratins; these cells were focally positive for GFAP, maspin, neuron-specific enolase, and cytokeratin 14. Alpha-smooth muscle actin, epithelial membrane antigen, carcinoembryonic antigen, collagen IV, Gp100 (HMB-45), and p63 were negative in neoplastic hyaline cells. Ultrastructural analysis disclosed cells with ovoid nuclei showing occasional invaginations and nuclear pockets; the cytoplasm was rich in meshworks of non-bundling intermediate filaments and a variable amount of rough endoplasmic reticulum cisternae. Based on our findings and those previously reported, hyaline cells of HCRCS might posses an aberrant myoepithelial differentiation. Most importantly, pathologists need to be aware of the histologic and immunohistochemical features of HCRCS to avoid a misdiagnosis of highly malignant neoplams, such as malignant melanoma and extra-skeletal myxoid chondrosarcoma.     

African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca2+-induced mitochondrial swelling

Objective

To evaluate the antioxidant and radical scavenging activities of Solanum anguivi fruit (SAG) and its possible effect on mitochondrial permeability transition pore as well as mitochondrial membrane potential (ΔΨ_m) isolated from rat liver.

Methods

Antioxidant activity of SAG was assayed by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, iron chelation and ability to inhibit lipid peroxidation in both liver and brain homogenate of rats. Also, the effect of SAG on mitochondrial membrane potential and mitochondrial swelling were determined. Identification and quantification of bioactive polyphenolics was done by HPLC-DAD.

Results

SAG exhibited potent and concentration dependent free radical-scavenging activity (IC₅₀/DPPH=275.03±7.8 µg/mL). Reductive and iron chelation abilities also increase with increase in SAG concentration. SAG also inhibited peroxidation of cerebral and hepatic lipids subjected to iron oxidative assault. SAG protected against Ca²⁺ (110 µmol/L)-induced mitochondrial swelling and maintained the ΔΨ_m. HPLC analysis revealed the presence of gallic acid [(17.54±0.04) mg/g], chlorogenic acid (21.90±0.02 mg/g), caffeic acid (16.64±0.01 mg/g), rutin [(14.71±0.03) mg/g] and quercetin [(7.39±0.05) mg/g].

Conclusions

These effects could be attributed to the bioactive polyphenolic compounds present in the extract. Our results suggest that SAG extract is a potential source of natural antioxidants that may be used not only in pharmaceutical and food industry but also in the treatment of diseases associated with oxidative stress.     

Central mucoepidermoid carcinoma of the mandible: report of four cases with long-term follow-up

Central mucoepidermoid carcinomas are uncommon tumours, representing about 2 to 4% of all mucoepidermoid carcinomas. They are histologically low-grade cancers, usually affecting the mandible as uni- or multilocular radiographic lesions. The authors report four cases of central mucoepidermoid carcinomas affecting the mandible and discuss their clinical, radiographic and histological findings. Four females were affected, with a mean age of 42 years and all cases involved the posterior mandible. Treatment included surgery in three cases and surgery associated to neck dissection and radiotherapy in one case. Two patients showed no recurrence and were alive without signs of the disease after a mean follow-up of 78 months. The other two patients showed local recurrence and one was alive with disease after a follow-up of 384 months, and the other was followed-up for 324 months dying by other causes without signs of the tumour. Central mucoepidermoid carcinomas of the mandible are low-grade tumours, and effective surgical treatment involving wide local excision or en bloc resection allows patients to have a favourable prognosis after long-term follow-up.     

In Vitro Assessment of NSAIDs-Membrane Interactions: Significance for Pharmacological Actions

Purpose

To study interactions between nonsteroidal anti-inflammatory drugs (NSAIDs) and membrane mimetic models.

Methods

The interactions of indomethacin and nimesulide with liposomes of dipalmitoylphosphatidylcholine (DPPC) at two physiological pH conditions (pH 7.4 and 5.0) were investigated by time-resolved and steady-state fluorescence techniques and derivative ultraviolet/visible absorption spectrophotometry. Fluorescence quenching studies that assess the location of the drugs interacting with the membrane were carried out using labeled liposomes with trimethylammonium-diphenylhexatriene (TMA-DPH), a fluorescent probe with well-known membrane localization. Partition of the drugs within membranes was determined by calculating their partition coefficients (K _p ) between liposomes and water using derivative ultraviolet/visible absorption spectrophotometry in a temperature range of 37–50°C. The Van’t Hoff analysis of the temperature dependence of K _p values allowed calculating the membrane-water variation of enthalpy (ΔH _w→m) and entropy (ΔS _w→m) and consequently the Gibbs free energy (ΔG _w→m).

Results

Results indicate that quenching, partitioning and thermodynamic parameters inherent to the interaction of the studied drugs with the membrane mimetic model are deeply dependent on the initial organization of the membrane, on the pH medium and on the physical properties of the drug.

Conclusions

The interactions between NSAIDs and membranes are manifested as changes in the physical and thermodynamic properties of the bilayers. Depending on the composition and physical state of the membrane and the chemical structure of the NSAID, the interaction can support or prevent drug activity or toxicity.     

Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive–compulsive disorder

Nearly one-third of patients with obsessive–compulsive disorder (OCD) fail to respond to adequate therapeutic approaches such as serotonin reuptake inhibitors and/or cognitive-behavioral therapy (CBT). This study investigated structural magnetic resonance imaging (MRI) correlates as potential pre-treatment brain markers to predict treatment response in treatment-naïve OCD patients randomized between trials of fluoxetine or CBT. Treatment-naïve OCD patients underwent structural MRI scans before randomization to a 12-week clinical trial of either fluoxetine or group-based CBT. Voxel-based morphometry was used to identify correlations between pretreatment regional gray matter volume and changes in symptom severity on the Yale–Brown Obsessive–Compulsive Scale (Y–BOCS). Brain regional correlations of treatment response differed between treatment groups. Notably, symptom improvement in the fluoxetine treatment group (n=14) was significantly correlated with smaller pretreatment gray matter volume within the right middle lateral orbitofrontal cortex (OFC), whereas symptom improvement in the CBT treatment group (n=15) was significantly correlated with larger pretreatment gray matter volume within the right medial prefrontal cortex (mPFC). No significant a priori regional correlations of treatment response were identified as common between the two treatment groups when considering the entire sample (n=29). These findings suggest that pretreatment gray matter volumes of distinct brain regions within the lateral OFC and mPFC were differentially correlated to treatment response to fluoxetine versus CBT in OCD patients. This study further implicates the mPFC in the fear/anxiety extinction process and stresses the importance of lateral portions of the OFC in mediating fluoxetine's effectiveness in OCD. Clinical registration information: http://clinicaltrials.gov-NCT00680602.     

Proposal for a new risk stratification classification for meningioma based on patient age,WHO tumor grade,size, localization,and karyotype

Background

Tumor recurrence remains the major clinical complication of meningiomas, the majority of recurrences occurring among WHO grade I/benign tumors. In the present study, we propose a new scoring system for the prognostic stratification of meningioma patients based on analysis of a large series of meningiomas followed for a median of >5 years.

Methods

Tumor cytogenetics were systematically investigated by interphase fluorescence in situ hybridization in 302 meningioma samples, and the proposed classification was further validated in an independent series of cases (n = 132) analyzed by high-density (500K) single-nucleotide polymorphism (SNP) arrays.

Results

Overall, we found an adverse impact on patient relapse-free survival (RFS) for males, presence of brain edema, younger patients (<55 years), tumor size >50 mm, tumor localization at intraventricular and anterior cranial base areas, WHO grade II/III meningiomas, and complex karyotypes; the latter 5 variables showed an independent predictive value in multivariate analysis. Based on these parameters, a prognostic score was established for each individual case, and patients were stratified into 4 risk categories with significantly different (P < .001) outcomes. These included a good prognosis group, consisting of approximately 20% of cases, that showed a RFS of 100% ± 0% at 10 years and a very poor-prognosis group with a RFS rate of 0% ± 0% at 10 years. The prognostic impact of the scoring system proposed here was also retained when WHO grade I cases were considered separately (P < .001).

Conclusions

Based on this risk-stratification classification, different strategies may be adopted for follow-up, and eventually also for treatment, of meningioma patients at different risks for relapse.     

Teamwork in the viscous oceanic microscale

Nutrient acquisition is crucial for oceanic microbes, and competitive solutions to solve this challenge have evolved among a range of unicellular protists. However, solitary solutions are not the only approach found in natural populations. A diverse array of oceanic protists form temporary or even long-lasting attachments to other protists and marine aggregates. Do these planktonic consortia provide benefits to their members? Here, we use empirical and modeling approaches to evaluate whether the relationship between a large centric diatom, Coscinodiscus wailesii, and a ciliate epibiont, Pseudovorticella coscinodisci, provides nutrient flux benefits to the host diatom. We find that fluid flows generated by ciliary beating can increase nutrient flux to a diatom cell surface four to 10 times that of a still cell without ciliate epibionts. This cosmopolitan species of diatom does not form consortia in all environments but frequently joins such consortia in nutrient-depleted waters. Our results demonstrate that symbiotic consortia provide a cooperative alternative of comparable or greater magnitude to sinking for enhancement of nutrient acquisition in challenging environments.

Global models of oxygen and carbon dioxide alterations depend upon transfer rates between small phytoplankton cells and surrounding surface waters of the world’s oceans (1–3). Although these cells are important on large scales, their individual interactions occur at microscopic dimensions that are dominated by viscosity. In this viscous environment, critical cellular processes, such as the exchange of nutrients, metabolites, and wastes, rely upon diffusion (4). While diffusion is an effective means of nutrient transport for the smallest microbes (5), it also creates a depleted region around the cell surface, referred to as the diffusion boundary layer (DBL), that limits nutrient consumption and cell growth (6, 7). The DBL for a cell at rest extends nine cell radii from the cell surface before the nutrient concentration reaches 90% of ambient levels (8), creating formidable disadvantages for nutrient acquisition by large cells requiring nutrient diffusion across large distances relative to their cell size (9). Phytoplankton have evolved mechanisms to mitigate the limitations of diffusive transfer rates by swimming or sinking (10) to generate relative motion between the cell and surrounding fluid. Diatoms—barrel-shaped, nonmotile eukaryotes—are considered to be one of the most ecologically important groups of phytoplankton (11–14) that absorb nutrients across their whole cell surface (15) but often increase sinking rates when experiencing nutrient limitation (16). Sinking thins the DBL surrounding the diatom cell and reduces the distance over which diffusion limits nutrient transport (8, 17). One potential disadvantage of this mechanism for DBL reduction is the high probability for a cell to sink out of sunlit regions, and sinking diatoms are major contributors to organic mass flux from surface to deep oceanic waters (1). A widespread but unevaluated alternative for such large cells involves teamwork with other smaller, motile cells that combine to form multicell consortia. Consortia are typically comprised of larger nonmotile host cells with smaller, surface-adhering motile cells termed epibionts. Although infrequently studied, epibionts are ubiquitous in the micrometer-scale world of planktonic organisms (18), and flagellated or ciliated epibionts often attach to larger objects (19) or marine snow (20). The selective forces favoring epibiont attachment remain in question. A range of fluid dynamic effects on prey encounter as well as biological factors such as reduced predator encounter risk or elevated prey availability surrounding host attachment sites have been proposed to explain the widespread nature of epibiont attachment (21, 22). However, the movement of motile epibiont cilia or flagella alters flows and, hence, creates an altered fluid dynamic environment surrounding the consortia. What are the consequences for the consortium host—does a larger, nonmotile cell benefit by membership in consortia? While advantages to the epibiont have been examined, the impacts on the host cells within a consortium have remained largely unconsidered. One reason for this is that physical associations between members of consortia are often temporary, and the short time scales of these relationships have hampered direct evaluation of the fluid mechanical interactions between consortium members.Here, we describe experimental work in combination with mathematical models that quantify the effect of the epibiont’s advective currents on nutrient availability to host cells within consortia formed by a large diatom, Coscinodiscus wailesii, and its peritrich ciliate epibiont, Pseudovorticella coscinodisci (Fig. 1A). Consortia composed of C. wailesii and P. coscinodisci are common along the Atlantic coast of South America (23, 24) and have provided a valuable opportunity for measuring fluid interactions characterizing a planktonic host–epibiont association.Open in a separate windowFig. 1.Diatom–ciliate association: (A) diatom C. wailesii and its epibiont P. coscinodisci. Scale bars represent 100 microns in length. (B) Flow around a single ciliate directed toward the diatom cell surface. (C) Velocity field for the same diatom–ciliate pair with a blue line indicating the transect line used for measurement of flow field velocities. The magenta segment represents the microcurrent component that directly intercepts the ciliary crown.