Many drugs for glaucoma treatment have recently been developed, but prostaglandin (PG) analogs, which are PGF2α derivatives, are used most frequently. In particular, PG analogs with a stem name of "-prost" have become first-line therapies. When using PG analogs, it is important to understand their chemical structures and characteristics. These PG analogs are biologically active in carboxylate forms and are formulated as prodrugs by esterifying the terminal carboxyl to reduce side effects. The effect of PG analogs on glaucoma is determined by the degree of affinity to prostaglandin FP receptors. the structural formulae of PG analogs and our experimental results suggest that a 15-difluoro PG analog (tafluprost), which has a 13, 14 double bond, would have greater affinity for prostaglandin FP receptors and greater stability than 15-hydroxy PG analogs. Furthermore, 15-difluoro PG analogs containing a 13, 14 double bond were effective in clinical studies. Experimental results have shown that 15-difluoro PG analogs could help improve blood flow in the eye and might reduce the side effect of pigmentation. Tafluprost has been considered the best PG analog for first-line therapy, but a series of new glaucoma eye drops containing 2 active ingredients were launched in Japan in 2010. Each eye drop has advantages and disadvantages, and further studies are necessary to evaluate their clinical usefulness.
The purpose of this study was to evaluate the safety and efficacy of chemoradiation therapy with docetaxel, nedaplatin and fluorouracil (5-FU) for patients older than 80 years with advanced esophageal cancer. Three patients were enrolled and received the combination of docetaxel (30mg/m2 on day 1), nedaplatin (10mg/body on days 1～5), and 5-FU (250mg/m2 on days 1～5) with radiation (50.4 to 60Gy in 1.8 to 2-Gy fractions over 6 weeks). Macroscopic and pathologic examinations after treatment showed no esophageal cancers; therefore complete responses were achieved in all patients, and the overall response rate was 100%. Myelosuppressions with grade 2 leukopenia occurred in 2 patients (66%), and grade 3 leukopenia occurred in 1 patient (33%). This chemoradiation therapy is effective and well tolerated by patients older than 80 years with advanced esophageal cancer.
Viral vectors are powerful tools for gene delivery and expression both in vitro and in vivo. Recently, many types of viral vectors have become commercially available and are easily used. It is important to choose appropriate viral vectors according to target cells and organs. In this technical note, we describe the characteristics of viral vectors and how to choose the appropriate viral vector to transduce target cells in vitro.
A 72-year-old woman was referred to our hospital with jaundice, right hypochondrial pain, and fever. Enhanced computed tomography revealed a greatly thickened gallbladder wall, a large gallstone (Φ33mm), and encasement of the right hepatic artery. Percutaneous transhepatic cholangiography revealed severe stenosis extending from the hilar bifurcation of the bile ducts to the common bile duct. Pathological examination of the gallbladder wall during surgery for gallstone ileus carried out 4 days after percutaneous transhepatic portal vein embolization led to a final diagnosis of xanthogranulomatous cholecystitis. Physicians need to be alert to the possibility of xanthogranulomatous cholecystitis, which is difficult to differentiate from advanced gallbladder cancer.
An 83-year-old man presented with supraclavicular and mediastinal lymph nodes swelling and elevated serum levels of neuron-specific enolase (NSE), pro-gastrin-releasing peptide (pro-GRP), and cytokeratin fragment (CYFRA). He underwent supraclavicular lymph node dissection. The pathological diagnosis was metastatic lymph node neuroendocrine carcinoma. The initial diagnosis was small cell lung carcinoma c-TxN3M0 III B with an unknown primary site, because fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) had revealed increased uptake in the neck and mediastinal lymphadenopathy, but no significant intrapulmonary uptake. However, computed tomography (CT) of the chest had detected a lesion, which was assumed to be a vessel, in the right lower lung. The patient underwent radiotherapy, and CT of the chest 1 month later revealed a partial response of the lymph nodes. However, at the same time, disease recurred in the skin adjacent to the site of supraclavicular lymph node dissection, and the lesion in the right lower lung enlarged. We suspected that this intrapulmonary lesion was the primary site. Metastasis to cervical and mediastinal lymph nodes from an unknown primary carcinoma is rare, and the primary site should be determined so that appropriate treatment can be performed. If the primary site cannot be determined with the initial examination, regular follow-up examinations with CT, magnetic resonance imaging, and FDG-PET should be performed.
Regular exercise plays an important role in preventing metabolic diseases, the impairment of cognitive function, and the onset of depression. Regular exercise enhances adult neurogenesis in the dentate gyrus of the hippocampus, and the exercise-derived prevention of cognitive deficits and depression is closely related to adult hippocampal neurogenesis. Both blood-derived factors and brain-derived factors are thought to contribute to the exercise-induced enhancement of adult hippocampal neurogenesis. Blood-derived factors include insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) . Exercise increases the transport of these substances from the blood to the brain and increases adult hippocampal neurogenesis. In contrast the exercise-induced enhancement of adult hippocampal neurogenesis can be blocked by inhibiting the binding of IGF-1 or VEGF to its receptor. On the other hand, brain-derived factors include brain-derived neurotrophic factor (BDNF) or Wnt3. In particular, BDNF plays a wide range of roles in neuronal development and survival, and the exercise-induced enhancement of hippocampal BDNF contributes to the increase in hippocampal neurogenesis. Aging and chronic stress impairs cognitive function, whereas regular exercise prevents age- or stress-induced impairment of cognitive function, the improvement of which is attributed to the action of IGF-1 or BDNF. In addition, the preventive effect of exercise on the onset of depression is also dependent on the improvement of hippocampal neurogenesis via BDNF or VEGF. These findings demonstrate that regular exercise helps maintain cognitive function and prevents depression in the elderly and the stressed; however, the mechanism of the exercise-induced improvement of cognition or depression remains unclear. Clarifying the mechanism via neuroscientific and molecular biological studies is needed to promote the usefulness of exercise for preventing cognitive deficits and depression.
Leukemias and sarcomas account for many of the pediatric cases of malignancy; indeed leukemia accounts for approximately 40% of cases. The basic treatment for pediatric malignancy is chemotherapy; however, the use of anticancer drugs may also damage normal cells in the body. This creates a problem of increased susceptibility to infection because of a weakened immune system. The use of antibiotics is therefore essential to prevent and treat infections. However, antibiotics can kill both pathogenic bacteria and useful bacteria. By disturbing the balance of intestinal bacteria, antibiotics may disrupt intestinal barrier function, thus, perversely increasing the risk of infection. In the present paper, we focus on the use of probiotics to improve the balance of intestinal bacteria. In particular, we examine the effectiveness of probiotics in children undergoing chemotherapy.
Anisakiasis is a disease characterized by the abrupt onset of sharp epigastric pain, typically a few hours after eating raw or undercooked seafood. At present, the most common effective treatment is endoscopic removal. However, over 23 years Yamamoto has used an antiallergic drug (Stronger Neo-Minophagen C) and prednisolone to treat more than 190 patients with anisakiasis diagnosed on the basis of symptoms and without endoscopy. In this report, Kurihara reconfirms the effectiveness of this unique treatment for patients with endoscopically diagnosed anisakiasis. On the basis of these findings, we propose that the combination therapy of an antiallergic drug and a corticosteroid is a reasonable, inexpensive, and safe method for treating anisakiasis.