Cytokine-rich autologous serum system for cartilaginous tissue engineering

Animal serum used for tissue engineering approaches has unacceptable risk for contamination with infectious agents. In this study, a cytokine-rich autologous serum (CRAS) system was developed. Canine auricular chondrocytes were cultured in medium supplemented with either fetal bovine serum (FBS) or autologous canine serum, alone or supplemented with basic fibroblast growth factor (b-FGF). Cell proliferative capacity was higher in the CRAS cultures than in those cultured in FBS, with greater expression of aggrecan and type II collagen in the b-FGF-supplemented CRAS group. The chondrocytes were seeded onto an ear-shaped biodegradable polymer (poly-L-lactide:epsilon-caprolactone, 50:50) and cultured in a Bioflow reactor for 1 week, using the 3 different culture media indicated above, and subsequently implanted into nude mice. The best outcome (cartilage gene expression and morphologic properties) was seen with tissue-engineered constructs precultured in the b-FGF-supplemented CRAS media. These findings indicate a clinically realizable approach for tissue engineering of cartilaginous structures.     

Ultradian oscillations of Stat, Smad, and Hes1 expression in response to serum

Serum response has been used as a model for studying signaling transduction for many biological events such as cell proliferation and survival. Although expression of many genes is up- or down-regulated after serum stimulation, the Notch effector Hes1 displays oscillatory response. However, the precise mechanism and biological significance of this oscillation remain to be determined. Here, we identified serum-induced ultradian oscillators, including molecules in Stat and Smad signaling. Stat and Smad oscillations involve activation of Stat3 and Smad1 and delayed negative feedback by their inhibitors Socs3 and Smad6, respectively. Moreover, Stat oscillations induce oscillatory expression of Hes1 by regulating its half-life, and loss of Hes1 oscillations leads to G(1) phase retardation of the cell cycle. These results indicate that coupled Stat and Hes1 oscillations are important for efficient cell proliferation and provide evidence that expression modes of signaling molecules affect downstream cellular events.     

Bladder preservation by chemoradiotherapy in combination with radical TUR-Bt in muscle invasive bladder cancer

PURPOSE: To evaluate bladder preservation protocol by radical TUR-Bt and subsequent concurrent chemoradiotherapy in muscle invasive bladder cancer. PATIENTS AND METHODS: Twenty-six patients with muscle invasive bladder cancer (T2-T4NOM0) were treated with concurrent chemoradiotherapy after transurethral resection of the tumor as much as possible beyond muscle layers. Chemotherapy was consisted of systemic administration of methoterexete (30 mg/m2 day 1 and day 22) and intraarterial infusion of cisplatin (70 mg/m2, day 2 and day 23). The response was evaluated by TUR, urine cytology, CT and/or MRI 4 to 6 weeks after the treatment. RESULTS: Among 24 evaluable cases, pathological complete response was achieved in 13 cases (50%) and residual tumors were noted in 11 cases (pT1 in 9 and pT2 in 2). During follow-up period up to 69.8 months, invasive recurrence was observed in 2 cases, superficial recurrence was noted in 5 patients and distant metastasis without evidence of local recurrence was noted in 4 cases. Overall bladder preservation rate was 92%. CONCLUSIONS: The bladder preservation by radical TUR-Bt and chemoradiotherapy is a safe and effective treatment option for muscle invasive bladder cancer.     

Significance of the soleal vein for the pathogenesis of deep vein thrombosis leading to acute massive pulmonary thromboembolism

Prophylaxis of deep vein thrombosis (DVT) is a serious matter as the source of pulmonary thromboembolism (PTE) in hospitalized patients. Leg DVT is classified into three groups: iliac, femoral and calf types. Among them, calf type DVT is closely connected with PTE. Especially, soleal vein is the most frequent site of thrombi formation occurring with venous stagnation. Although most cases of soleal vein thrombosis are resolved soon without specific treatments: in around 20% of cases the thrombosis propagates to the proximal drainage vein as float thrombi e.g. from peroneal vein and posterior tibial vein to popliteal vein. Thereafter, the organization of thrombi leads to venous valve insufficiency, so-called postthrombotic syndrome. As a result, it worsens blood stagnation and induces recurrent thrombi formation. The broad prophylaxis of DVT in the soleal veins for inpatients is the most important point in the initial stage of hospitalization.     

Critical alkalosis following intraperitoneal irrigation with sodium bicarbonate in a patient with pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a rare disease, presenting with large amounts of mucinous ascites, and treatment with intraperitoneal irrigation with mucolytic agents has been tried. We report a patient with PMP who underwent intraperitoneal irrigation with sodium bicarbonate and exhibited marked alkalosis. The patient was a 78-year-old woman who had mucinous ascites, and an appendiceal and an ovarian tumor. Bilateral salpingo-oophorectomy and appendectomy were performed, and she then underwent intraperitoneal irrigation with sodium bicarbonate (7%, 1000 ml). Shortly after the irrigation, blood gas analysis showed critical alkalosis (pH, 7.66; base excess [BE], 24 mEq x l(-1); HCO3 (-), 50 mEq x l(-1)) with electrolyte imbalance (Na+, 153 mEq x l(-1); K+, 2.8 mEq x l(-1); Ca2+, 0.98 mEq x l(-1), Cl(-1), 99 mEq x l(-1)). The alkalosis and electrolyte imbalance were ameliorated with the administration of potassium chloride and calcium chloride intravenously, and the patient was extubated after the 2-h surgical procedure. The patient was discharged home after 15 days without problems. Sodium bicarbonate may be an effective mucolytic agent for PMP. However, during irrigation with sodium bicarbonate, careful evaluation of the acid-base balance and serum electrolytes, and prompt treatment of alkalosis or electrolyte imbalance, should this occur, are of great importance.     

The process of whistleblowing in a Japanese psychiatric hospital

This study aims to unveil the process of whistleblowing. Two nursing staff members who worked in a psychiatric hospital convicted of large-scale wrongdoing were interviewed. Data were analyzed using a modified grounded theory approach. Analysis of the interviews demonstrated that they did not decide to whistleblow when they were suspicious or had an awareness of wrongdoing. They continued to work, driven by appreciation, affection, and a sense of duty. Their decision to whistleblow was ultimately motivated by firm conviction. Shortly after whistleblowing, wavering emotions were observed, consisting of a guilty conscience, fear of retribution, and pride, which subsequently transformed to stable emotions containing a sense of relief and regret for delayed action. It is necessary for nurses to recognize that their professional responsibility is primarily to patients, not to organizations. Nurses should also have professional judgment about appropriate allegiance and actions.     

Rapid changes in amino acid and polyamine metabolism during copper-induced cell death of human gingival fibroblast

There are very few studies on the interaction between dental alloys and oral tissues. The effect of direct contact with copper (Cu) on the cellular function of human gingival fibroblast (HGF) derived from the periodontal tissues was investigated. When HGF cells were inoculated onto a Cu plate, the viability of HGF cells immediately declined. This was accompanied by vacuolization and chromatin condensation near the nuclear membrane. The intracellular concentration of spermidine and spermine declined, whereas that of putrescine slightly increased. Amino acid analysis of the medium revealed that glutamine was consumed at the greatest rate, amounting to more than half of the total amino acid consumption. Contact with the Cu plate resulted in the complete elimination of glutamine utilization and a simultaneous increase in the production of most amino acids, possibly due to enhanced proteolysis. This was accompanied by a time-dependent increase in the consumption of cystine, possibly due to oxidative reactions, and the enhanced production of glycine and glutamic acid. These data suggest that the contact with the Cu plate induced non-apoptotic cell death in HGF cells, which was tightly coupled with a rapid dysfunction of amino acid and polyamine metabolism.