Effects of acute and chronic administration of the melanocortin agonist MTII in mice with diet-induced obesity

High-fat diet-induced obesity (DIO) in rodents is associated with hyperleptinemia and resistance to leptin, but the response to agents acting downstream of leptin receptors remains unknown. We assessed the response of mice with DIO to treatment with MTII, an alpha-melanocyte-stimulating hormone analog. MTII delivered four times daily by intraperitoneal injection to C57BL/6J mice produced a dose-responsive effect on food intake, body weight, leptin, corticosterone, insulin, and free fatty acids. In DIO mice, administration of MTII 100 microg q.i.d. i.p. markedly suppressed feeding during the first 4 days of treatment, with food intake returning to control levels at day 5. Progressive weight loss also occurred over the first 4 days, after which weight plateaued at a level below control. After 8 days of treatment, MTII-treated DIO mice had major suppression of both leptin and insulin levels. Central administration of MTII for 4 days (10 nmol/day) in DIO mice significantly suppressed food intake, induced weight loss, and increased energy expenditure. These results indicate that 1) MTII administration to DIO mice causes suppression of food intake and body weight loss, and decreased food intake is primarily responsible for weight loss; 2) peripheral MTII improves insulin resistance in DIO mice; 3) "tachyphylaxis" to the effect of chronic MTII treatment on food intake occurs; and 4) at least some of the effects of MTII are exerted centrally. In conclusion, treatment with a melanocortin agonist is a promising therapeutic approach to DIO and associated insulin resistance.     

Cytotoxic and genotoxic effects of paraquat in Hordeum vulgare and human lymphocytes in vitro

Two phylogenetically distant types of test‐systems—root tip meristems of barley (Hordeum vulgare) and human lymphocytes in vitro were used to detect genotoxicity and cytotoxicity induced by the herbicide paraquat (PQ) in the concentration range (10^?6 to 5 × 10^?4 mol/l). As an endpoint for cytotoxicity the mitotic index (MI) was evaluated. The frequency of chromosome aberrations (CA) and the frequency of micronuclei (MN) were used as endpoints for genotoxicity. A dose‐dependent increase of CA and MN was observed in both test systems, although the values for PQ‐induced MN were somewhat lower. The increase of the genotoxic effect corresponds to a decrease of mitotic activity. The structurally reconstructed barley karyotype MK14/2034 allowed the allocation of the PQ‐specific features of aberration distribution patterns and gave information about which chromosome segments in different chromosomal positions were involved in induced aberrations. Paraquat produced preferably isochromatid breaks and “aberration hot spots” in a restricted number of heterochromatin‐containing segments. The comparative analysis of susceptibility in the used test‐systems to PQ with respect to its cytotoxic and clastogenic effect showed that the human lymphocytes were more sensitive than Hordeum vulgare. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

Are bony pelvis dimensions associated with levator ani defects? A case–control study

Introduction and hypothesis

Bony pelvis dimensions have been shown to differ in women with and without pelvic floor dysfunction. The goal of this study was to determine whether bony pelvis dimensions are different when comparing women with severe bilateral levator ani defects (LAD) with those with normal muscles.

Methods

This is a secondary analysis of a case–control study comparing women with and those without pelvic organ prolapse. Subjects underwent pelvic organ prolapse quantification (POP-Q) examination and were classified as either having prolapse or being normal. All underwent pelvic magnetic resonance imaging (MRI). Levator defects were assessed based on the muscles’ appearance on imaging and subjects were stratified into two groups—women with normal muscles (n?=?99) and women with severe bilateral LAD (n?=?50). Bony pelvis dimensions were measured via MRI pelvimetry. The subpubic angle, interspinous and intertuberous diameters, and the sacrococcygeal joint-to-infrapubic point (SCIPP) lengths were compared.

Results

Both groups had similar demographics. The SCIPP length was 2.5 % (3 mm) shorter in women with severe LAD than in those without defects (P?=?0.02). The SCIPP measured 4 % (5 mm) less in women with prolapse and severe LAD than in subjects with prolapse but normal muscles (P?=?0.01). Logistic regression identified SCIPP length and history of forceps delivery as being independent predictors of severe bilateral LAD.

Conclusions

Severe bilateral LAD are associated with shorter SCIPP length and forceps-assisted vaginal delivery.     

The Treatment of High Grade Gliomas and Diffuse Intrinsic Pontine Tumors of Childhood and Adolescence: A Historical – and Futuristic – Perspective

Summary Pediatric high grade gliomas represent a heterogeneous group of tumors with poor prognoses despite the use of multimodal treatment. Very little progress has been made over the past decades in identifying efficacious therapeutic modalities against both high grade gliomas and diffuse brainstem gliomas in children. The degree of surgical resection is the most important clinical prognostic factor for children with high grade gliomas, and a complete resection should be attempted whenever feasible. The role of radiation therapy in the treatment of older children with high grade gliomas and diffuse brain stem gliomas is undisputed; however the benefit of using radiation for patients less than 6 years of age (with high grade gliomas) might be questionable. Despite the absence of solid evidence to support its use, chemotherapy is routinely used against these tumors. Currently temozolomide is being investigated due to its activity in adult trials and based on preliminary data regarding recurrent disease. A small subgroup of patients can be successfully treated with high dose chemotherapy followed by autologous stem cell rescue. Early trials using this modality in the past had been associated with high morbidity and mortality. High dose chemotherapy with autologous stem cell rescue in selected patients with minimal residual disease, angiogenesis inhibitors, radiosensitizers and other biological modifiers are being currently investigated in phase I/II trials.     

Tibial shaft fracture after removal of an ACE tibial nail

Intramedullary interlocking nailing is the gold standard method for treatment of tibial shaft fractures. Thus, the growing use of the intramedullary nailing resulted in an increased number of tibial nails removal procedures in daily clinical practice. Despite adequate surgeon experience, the removal of tibial intramedullary nails is not without complications. One of the commonly used nails is the ACE (DePuy Orthopaedics, Inc., Warsaw, IN, USA). The purpose of this paper is to report such a complication following the removal procedure and review the pertinent literature. A 39-year-old female who had sustained a lower-third tibial fracture was treated with an intramedullary nail 5 years ago. Despite her unremarkable follow-up, for personal reasons, a removal procedure was planned. Two undisplaced fractures were observed in the postoperative radiological evaluation. The potential complications of the removal of intramedullary nailing of the tibia should be considered by both physician and patient.     

The Shape/Morphology Balance: A Study of Stealth Liposomes via Fractal Analysis and Drug Encapsulation

Purpose

Fractal analysis was used as a tool in order to study the morphological characteristics of PEGylated liposomes. We report on the morphological characteristics of stealth liposomes composed of DPPC and DPPE-PEG 3000 in two dispersion media using fractal analysis.

Methods

Light scattering techniques were used in order to elucidate the size, the morphology and the surface charge of PEGylated liposomes as a function of PEGylated lipid concentration and temperature. Fluorescence spectroscopy studies revealed a microenvironment of low polarity inside the liposomal membranes.

Results

All formulations were found to retain their physicochemical characteristics for at least 3 weeks. The hydrodynamic radii (R_h) of stealth liposomes were stable in the process of heating up to 50°C; while the fractal dimension values (d_f) which correspond to their morphology, have been changed during heating. Hence, these results are a first indication of the presence of a heterogeneous microdomain structure of the stealth liposomal system. The amphiphilic drug indomethacin (IND) was successfully encapsulated within the liposomes and led to an increased size of stealth liposomes, while the morphology of liposomal vectors changed significantly at the highest molar ratio of PEGylated lipid.

Conclusions

We can state that this approach can promote a new analytical concept based on the morphological characteristics and quantify the shape of drug carriers complementary to that of the conventional analytical techniques.     

Measurements of elastic modulus for human anterior lens capsule with atomic force microscopy: the effect of loading force

The purpose of the study was to appraise the effect of loading force magnitude on the determination of the elastic modulus of the anterior lens capsule through atomic force microscopy. Four human anterior lens capsules taken during phacoemulsification cataract surgery were studied, free of epithelial cells, with atomic force microscopy. For the experiment, five different indentation loading forces were applied to near areas of the specimen. Experimental data was exported and analyzed according to the Hertz model to obtain the Young’s modulus with regards to the elastic behavior of the material. Force–distance curves were acquired by applying a load of 2, 5, 10, 20 and 30 nN. When examining the results it was evident that determination of Young’s modulus of the anterior lens capsule is dependent on the loading force concerning the examined range. Loading forces of 10 and 20 nN led to results without significant difference (p > 0.05) and more reproducible (coefficients of variation 12.4 and 11.7 %, respectively).