A Comparison between the Effects of Hydrophobic and Hydrophilic Statins on Osteoclast Function In Vitro and Ovariectomy-Induced Bone Loss In Vivo

Statins potently inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase, blocking downstream biosynthesis of isoprenoid lipids and causing inhibition of protein prenylation. Prenylated signaling molecules are essential for osteoclast function, consistent with our previous observation that mevastatin can inhibit osteoclast activity in vitro. Several reports suggest that statins may also have an anabolic effect on bone and stimulate osteoblast differentiation. This study sought to determine the effects of both hydrophobic and hydrophilic statins, particularly rosuvastatin (RSV), on osteoclast function in vitro and in vivo. All statins tested (RSV, pravastatin [PRA], cerivastatin [CER], and simvastatin [SIM]) caused accumulation of unprenylated Rap-1A in rabbit osteoclast-like cells and J774 macrophages in vitro and inhibited osteoclast-mediated resorption. The order of potency for inhibiting prenylation in vitro (at concentrations of 0.01–50 μM) was CER > SIM > RSV > PRA. The most potent hydrophilic statin (CER, 0.05 and 0.3 mg/kg) inhibited prenylation in rabbit osteoclasts 24 hours after a single subcutaneous (s.c.) injection more effectively than the most potent hydrophobic statin (RSV, 20 mg/kg). However, in a mouse model of osteoporosis, s.c. 0.05 mg/kg/day CER and 2 or 20 mg/kg/day RSV for 3 weeks only mildly prevented loss of cortical and trabecular bone induced by ovariectomy. No increase in bone formation rate was observed with statin treatment, suggesting that this effect was due to inhibition of osteoclast-mediated resorption rather than increased bone formation.     

Special Variants of Differentiated Thyroid Cancer: Does It Alter the Extent of Surgery Versus Well-Differentiated Thyroid Cancer?

Introduction Recently, more aggressive variants of so-called well-differentiated thyroid carcinomas have been identified such as the tall cell variant, columnar cell variant, diffuse sclerosing variant, insular carcinoma, and Hürthle cell (oncocytic, oxyphilic) carcinomas. Methods An evidence-based review was performed to identify the optimal treatment recommendations for these thyroid cancers of intermediate differentiation. Conclusions Although some variation exists within the group, aggressive surgical and medical management are recommended for these neoplasias. Any such recommendations should, however, be viewed in the light of the fact that the current literature mainly consists of case reports, case series, and limited reviews. The clinical presentation, pathophysiology, diagnosis, and surgical and medical management for these thyroid cancers with intermediate differentiation are discussed.     

Differential uptake and cross‐presentation of soluble and necrotic cell antigen by human DC subsets

Cross‐presentation is the mechanism by which exogenous Ag is processed for recognition by CD8⁺ T cells. Murine CD8α⁺ DCs are specialized at cross‐presenting soluble and cellular Ag, but in humans this process is poorly characterized. In this study, we examined uptake and cross‐presentation of soluble and cellular Ag by human blood CD141⁺ DCs, the human equivalent of mouse CD8α⁺ DCs, and compared them with human monocyte‐derived DCs (MoDCs) and blood CD1c⁺ DC subsets. MoDCs were superior in their capacity to internalize and cross‐present soluble protein whereas CD141⁺ DCs were more efficient at ingesting and cross‐presenting cellular Ag. Whilst cross‐presentation by CD1c⁺ DCs and CD141⁺ DCs was dependent on the proteasome, and hence cytosolic translocation, cross‐presentation by MoDCs was not. Inhibition of endosomal acidification enhanced cross‐presentation by CD1c⁺ DCs and MoDCs but not by CD141⁺ DCs. These data demonstrate that CD1c⁺ DCs, CD141⁺ DCs, and MoDCs are capable of cross‐presentation; however, they do so via different mechanisms. Moreover, they demonstrate that human CD141⁺ DCs, like their murine CD8α⁺ DC counterparts, are specialized at cross‐presenting cellular Ag, most likely mediated by an enhanced capacity to ingest cellular Ag combined with subtle changes in lysosomal pH during Ag processing and use of the cytosolic pathway.     

Gastrointestinal nematode infections in German sheep

The objective of the present study was to determine the prevalence and variation of natural gastrointestinal nematode (GIN) infections in lambs according to birth type, gender and breed based on individual faecal egg counts (FEC) from various regions in Germany. A total of 3,924 lambs (3 to 15 months old) with different genetic backgrounds (Merinoland, German Blackhead Mutton, Rhoen, Texel and Merino long-wool) were individually sampled during the grazing period between 2006 and 2008. Furthermore, pooled faecal samples from each of the farms were cultured in order to differentiate the third-stage larvae of the nematode spp. Sixty-three percent of the lambs were infected with GIN. The infections were mostly low to moderate and involved several nematode species. The Trichostrongylus spp. was the predominant species based on the percentage of larvae in faecal cultures. Only 11.4% of the lambs were free of Eimeria oocysts. Tapeworm eggs were encountered in 13.2% of all samples. The prevalence of GIN infections varied significantly (P < 0.001) among farms. A significantly higher FEC (P < 0.05) was observed in multiple-born lambs when compared with singletons. Moreover, male lambs were more susceptible to infection than females (P < 0.001). No significant differences (P > 0.05) were observed between breeds regarding FEC. Inter-individual variations were higher than inter-breed differences, which may indicate the possibility of selection within these breeds for parasites resistance as described in earlier studies.     

A delayed diagnosis of congenital midline cervical cleft

Congenital midline cervical cleft (CMCC) is an extremely rare anomaly of the neck that typically presents in the neonatal period as a thin suprasternal vertical band of erythematous skin with a nipple‐like projection. We present the management of this uncommon and rarely described entity in a 9‐year‐old girl.     

A rare case of metastatic small cell carcinoma of breast from mixed types of cervical carcinoma

Metastatic small cell carcinoma to the breast from the uterine cervix is an extremely rare case. We report a case of a 58-year-old postmenopausal woman who presented with postmenopausal bleeding. Further investigations confirmed the diagnosis of mixed types of squamous and small cell cervical carcinoma. She underwent chemoradiotherapy and brachytherapy. A few months later, she presented with a palpable left breast lump three months after the diagnosis. Diagnosis of metastatic small cell carcinoma of the breast was confirmed by biopsy. Due to its rarity, we report on this case along with its relevant literature review.