Solitary bone metastasis in the tibia as a presenting sign of endometrial adenocarcinoma: a case report and the review of the literature

Background Metastasis to bone from endometrial adenocarcinoma is rare, when metastasises it usually locates in axial skeleton. Metastasis to extremities is extremely rare. Additionally the detection of the bone metastasis as a presenting feature is uncommon. In the present study we report the 10th cases of bone metastasis in the literature which located at tibial diaphysis and originated from endometrial adenocarcinoma as a presenting feature of the primary disease. Case Single tibial lesion was observed in a 70 years old woman. Biopsy confirmed metastatic adenocarcinoma of the unknown origin. We couldn’t find the primary origin with aggressive work-up. Tibial lesion regressed with radiotherapy. Endometrial adenocarcinoma is detected after the end of disease-free one year with the symptom of vaginal bleeding. After 47 months from initial tibial lesion and 35 months from gynaecologic operation, patient is still alive and disease free. Discussion Patients with endometrial adenocarcinoma presenting an isolated skeletal metastasis may exhibit an unusual group with a better prognosis. This study was presented as a poster exhibition at the 5th Meeting of Asia-Pasific Musculo Skeletal Tumour Society held between 23 and 25, April 2004, Izmir, Turkey.     

Development of Orally Applicable,Combinatorial Drug–Loaded Nanoparticles for the Treatment of Fibrosarcoma

Nanoparticulate systems have been receiving a significant attention especially for the treatment of cancer but one of the main hurdles is to produce these developed and high-tech nanosystems in large quantities. Anticancer drug formulations are generally designed for parenteral administrations but oral administration is still the most convenient route. In this study, orally applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared using Nano Spray Dryer. It is possible to produce these NPs in large quantities by simply increasing the processing time using the machine without changing any parameter. A chemotherapeutic agent (imatinib mesylate; IMA) and nonsteroidal anti-inflammatory drug (dexketoprofen trometamol) were loaded together in these NPs. NPs were also functionalized with polyethylene glycol and folic acid to obtain long circulating NPs and tumor targeting. The antitumoral activities of formulations showed that these developed NPs can enhance the effectiveness. Animal experiments were performed on fibrosarcoma-bearing mice model, and the treatment with 0.8 mg/μL/kg IMA-loaded chitosan NPs was found to be successful to slow down the growth of tumors. The tumor tissues were removed from the animals and enzymatic activities were evaluated. The inhibitory effect of tyrosine kinase was found to be enhanced from 36.4% to 68.4% when IMA was used in combination with dexketoprofen trometamol. Furthermore, all dried NPs were found to be stable for more than a year at 25°C. Presented results show that these developed combinatorial drug–loaded NPs can be used for the treatment of fibrosarcoma, and these data can provide an insight, new strategies for productions or alternatives in cancer treatment.     

Brain‐dead donor heart conservation with a preservation solution supplemented by a conditioned medium from mesenchymal stem cells improves graft contractility after transplantation

Hearts are usually procured from brain‐dead (BD) donors. However, brain death may induce hemodynamic instability, which may contribute to posttransplant graft dysfunction. We hypothesized that BD‐donor heart preservation with a conditioned medium (CM) from mesenchymal stem cells (MSCs) would improve graft function after transplantation. Additionally, we explored the PI3K pathway's potential role. Rat MSCs‐derived CM was used for conservation purposes. Donor rats were either exposed to sham operation or brain death by inflation of a subdural balloon‐catheter for 5.5 hours. Then, the hearts were explanted, stored in cardioplegic solution‐supplemented with either a medium vehicle (BD and sham), CM (BD + CM), or LY294002, an inhibitor of PI3K (BD + CM + LY), and finally transplanted. Systolic performance and relaxation parameters were significantly reduced in BD‐donors compared to sham. After transplantation, systolic and diastolic functions were significantly decreased, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL)‐positive cells and endonuclease G positive cells were increased in the BD‐group compared to sham. Preservation of BD‐donor hearts with CM resulted in a recovery of systolic graft function (dP/dt_max: BD + CM: 3148 ± 178 vs BD: 2192 ± 94 mm Hg/s at 110 µL, P < .05) and reduced apoptosis. LY294002 partially lowered graft protection afforded by CM in the BD group. Our data suggest that PI3K/Akt pathway is not the primary mechanism of action of CM in improving posttransplant cardiac contractility and preventing caspase‐independent apoptosis.     

Beyond bone biology: Lessons from team science

Today, research in biomedicine often requires the knowledge and technologies in diverse fields. Therefore, there is an increasing need for collaborative team science that crosses traditional disciplines. Here, we discuss our own lessons from both interdisciplinary and transdisciplinary teams, which ultimately ushered us to expand our research realm beyond bone biology.     

Expression profile of Toll-like receptor 4 in rat testis and epididymis throughout postnatal development

Toll-like receptors (TLRs) belonging to pattern recognition receptors are involved in maintaining testicular and epididymal immune homeostasis. The purpose of the current study was to investigate TLR4 expression in rat testis and epididymis throughout postnatal development. Weak staining was detected in peritubular myoid cells and immature Sertoli cells while no staining was observed in gonocytes during prepubertal period. However, TLR4 expression began to appear in spermatocytes in pubertal period and gradually increased in spermatids. An intense staining was observed in steps 5–19 spermatids in post pubertal and mature periods. Similarly, TLR4 expression in the testes steadily increased from pubertal period to mature period. Puberty also caused a significant increase in TLR4 expression in epididymis. TLR4 expression in cauda epididymis was lower as compared to those of other epididymal segments. The majority of epididymal epithelial cells exhibited apical TLR4 expression, whereas basal cells showed intense intracytoplasmic immunoreaction. We detected an intense staining in epididymal smooth muscle cells. The expression levels of TLR4 showed dynamic changes in both spermatogenic cells, and entire testicular and epididymal tissues during postnatal development. These results suggest that TLR4 expression contributes not only to inflammation but also to the development of spermatogenic cells.     

The effect of Ramadan fasting on kidney function in patients with chronic kidney disease

International Urology and Nephrology - Because of the increase in globalization, clinicians all over the world are confronted the questions about safety of Ramadan fasting. However, there is no...     

Delay‐dependent feedforward control of time‐delay systems with parametric uncertainties via dynamic IQCs

This paper studies the design problem of a robust delay‐dependent H _∞ feedforward controller design for a class of linear uncertain time‐delay system having state and control delays when the system is subject to ‐type disturbances. The proposed controller scheme involves two main controllers, which are static state‐feedback and dynamic feedforward controllers. The state‐feedback controller is used for stabilizing the delay and uncertainty‐free system, whereas the feedforward controller performs disturbance attenuation. Dynamic type integral quadratic constraints (IQCs), which consist of frequency‐dependent multipliers, have been introduced to represent the delays and parametric uncertainties in the system where the degree of the multiplier used in IQC representation is in an adjustable nature. This scheme allows the designer to obtain less conservative controllers with increasing precision. Sufficient delay‐dependent criteria in terms of linear matrix inequalities are obtained such that the uncertain linear time‐delay system is guaranteed to be globally, uniformly, asymptotically stable with a minimum disturbance attenuation level. Several numerical examples together with the simulation studies provided at the end illustrate the usefulness of the proposed design. Copyright © 2012 John Wiley & Sons, Ltd.     

A case report of doxycycline induced esophageal and gastric ulcer.

It is well-established that various drugs can induce esophageal and gastric mucosal injury. Generally neither motility disorder nor an anatomical stricture is found in such cases and the cause of mucosal injury is usually found to be inadequate fluid intake with medicine or consumption just prior to bedtime. Athough there are some case reports of doxycycline induced esophageal mucosal injury, doxycycline induced gastric ulcer has been reported only once in the literature. In this case report, a 33 year old female patient who had been prescribed doxycycline for pelvic inflammatory disease is presented. She was admitted with retrosternal and epigastric pain and odynophagia, which had begun after taking the second oral dose of the drug. Endoscopic examination showed ulcers in the mid esophagus and fundus of the stomach. Histologic findings supported a drug induced etiology in these ulcers. This is only the second case in the literature where gastric ulcer has been caused by doxycycline.