Life-Threatening Acute Hyponatremia with Generalized Seizure Induced by Low-Dose Cyclophosphamide in a Patient with Breast Cancer

Cyclophosphamide is commonly used in the treatment of malignant diseases. Symptomatic severe hyponatremia induced by low-dose cyclophosphamide is very uncommon worldwide. Recently we experienced a case of a 56-year-old woman with breast cancer who developed severe hyponatremia with generalized seizure after the first cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide. Her laboratory test showed a serum sodium of 116 mmol/L. Her hyponatremia was initially treated with hypertonic saline solution and furosemide. She completely recovered without neurological deficits after slow correction of the serum sodium concentration over two days. Clinicians must always keep in mind that life-threatening acute hyponatremia can be induced by intravenous cyclophosphamide during chemotherapy, even if the dosage is low

Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer

Introduction Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer. Patients and methods In this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints. Results A total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6–44.0, p < 0.001) and callipers (NCT 83.9% vs. NET 71.3%, 95% CI 0.4–24.9, p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p < 0.005). No difference existed in the conversion rate of BCS (13.8% for NCT vs. 11.5% for NET, p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group. Conclusions Better clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET. Trial registration Clinicaltrials.gov, NCT01622361. Registration June 19, 2012.This work was supported by the AstraZeneca Korea

Rising Incidence of Hip Fracture in Gwangju City and Chonnam Province, Korea

The purpose of study was to determine the incidence of hip fracture in 2001, to compare this with that of 1991, and to identify possible causes of change. Patients aged 50 yr or more living in Gwangju City and Chonnam Province, Korea, and who sustained a fracture of the hip during 2001 were investigated. Only patients who were admitted to hospitals for primary treatment of the first hip fracture were selected. There were 1,152 patients. A comparison of fracture incidences for 1991 and 2001 showed considerable increase during the 10-yr period. The total annual number of hip fractures rose from 247 in 1991 to 1,152 in 2001 and the fracture incidence also increased remarkably from 3.3 persons per 10,000 population in 1991 to 13.3 in 2001, representing a 4-fold increase over 10-yr. The reasons for this rising trend of hip fracture were not fully explained. However, an increase in the elderly population, an increase in osteoporosis, and an increase in injurious falls could partly account for the observed increase

Label-free affinity screening, design and synthesis of inhibitors targeting the <i>Mycobacterium tuberculosis</i> L-alanine dehydrogenase

The ability of Mycobacterium tuberculosis (Mtb) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies

Microfabricated ratchet structures for concentrating and patterning motile bacterial cells

We present a novel microfabricated concentrator for Escherichia coli that can be a stand-alone and self-contained microfluidic device because it utilizes the motility of cells. First of all, we characterize the motility of E. coli cells and various ratcheting structures that can guide cells to move in a desired direction in straight and circular channels. Then, we combine these ratcheting microstructures with the intrinsic tendency of cells to swim on the right side in microchannels to enhance the concentration rates up to 180 fold until the concentrators are fully filled with cells. Furthermore, we demonstrate that cells can be positioned and concentrated with a constant spacing distance on a surface, allowing spatial patterning of motile cells. These results can be applied to biosorption or biosensor devices that are powered by motile cells because they can be highly concentrated without any external mechanical and electrical energy sources. Hence, we believe that the concentrator design holds considerable potential to be applied for concentrating and patterning other motile microbes and providing a versatile structure for motility study of bacterial cells.close6

Anti-adhesive Effect and Safety of Sodium Hyaluronate and Sodium Carboxymethyl Cellulose Solution in Thyroid Surgery

A number of researchers have suggested the use of sodium hyaluronate carboxymethyl cellulose (HA-CMC) membrane for preventing postoperative adhesion. This study evaluated the anti-adhesive effect and safety of a newly developed HA-CMC solution in thyroidectomy. Methods: Seventy-four patients who underwent thyroidectomy were prospectively randomized. In the study group of 38 patients, 5 mL HA-CMC solution was applied to the operative field after thyroidectomy. The subjects were asked about adhesive symptoms using a four-item questionnaire at 2 weeks, 2 months and 6 months after surgery. In addition, three items on the appearance of neck wrinkles and scars were evaluated by a physician. Each item was scored from 0 to 10. Results: The mean (± standard deviation) total adhesion score at each visit was 15.22 ± 8.99, 10.42 ± 8.41, and 7.24 ± 5.83 for the control group and 19.29 ± 9.71, 9.46 ± 5.71, and 6.03 ± 4.32 for the study group. Total adhesion scores for both groups decreased with time (p 0.066). There were no complications related to the HA-CMC solution. Conclusion: The HA-CMC solution did not decrease subjective or objective postoperative adhesion in patients undergoing thyroid surgery, although it was biologically safe

Molecular mechanisms underlying the enhancement of carbon ion beam radiosensitivity of osteosarcoma cells by miR-29b.

Carbon ion radiotherapy (CIRT) is more effective than conventional photon beam radiotherapy in treating osteosarcoma (OSA); however, the outcomes of CIRT alone are still unsatisfactory. In this study, we aimed to investigate whether miR-29b acts as a radiosensitizer for CIRT. The OSA cell lines U2OS and KHOS were treated with carbon ion beam alone, gamma-ray irradiation alone, or in combination with an miR-29b mimic. OSA cell death as well as invasive and migratory abilities were analyzed through viability, colony formation, Transwell, and apoptosis assays. miR-29 expression was downregulated in OSA tissues compared to that in normal tissues and was associated with metastasis and relapse in patients with OSA. Further, miR-29b was found to directly target the transcription factor Sp1 and suppress the activation of the phosphatase and tensin homolog (PTEN)-AKT pathway. Conversely, Sp1 was found to attenuate the inhibitory effects of miR-29b in OSA cells. When used in combination with miR-29b mimic, carbon ion beam markedly inhibited invasion, migration, and proliferation of OSA cells and promoted apoptosis by inhibiting AKT phosphorylation in a Sp1/PTEN-mediated manner. Taken together, miR-29b mimic improved the radiosensitivity of OSA cells via the PTEN-AKT-Sp1 signaling pathway, presenting a novel strategy for the development of carbon ion beam combination therapy

Molecular mechanisms underlying the enhancement of carbon ion beam radiosensitivity of osteosarcoma cells by miR-29b.

Carbon ion radiotherapy (CIRT) is more effective than conventional photon beam radiotherapy in treating osteosarcoma (OSA); however, the outcomes of CIRT alone are still unsatisfactory. In this study, we aimed to investigate whether acts as a radiosensitizer for CIRT. The OSA cell lines U2OS and KHOS were treated with carbon ion beam alone, γ-ray irradiation alone, or in combination with an mimic. OSA cell death as well as invasive and migratory abilities were analyzed through viability, colony formation, Transwell, and apoptosis assays. expression was downregulated in OSA tissues compared to that in normal tissues and was associated with metastasis and relapse in patients with OSA. Further, was found to directly target the transcription factor Sp1 and suppress the activation of the phosphatase and tensin homolog (PTEN)-AKT pathway. Conversely, Sp1 was found to attenuate the inhibitory effects of in OSA cells. When used in combination with mimic, carbon ion beam markedly inhibited invasion, migration, and proliferation of OSA cells and promoted apoptosis by inhibiting AKT phosphorylation in a Sp1/PTEN-mediated manner. Taken together, mimic improved the radiosensitivity of OSA cells via the PTEN-AKT-Sp1 signaling pathway, presenting a novel strategy for the development of carbon ion beam combination therapy