Inhibitory/Suppressive oligodeoxynucleotide nanocapsules as simple oral delivery devices for preventing atopic dermatitis in mice

Advance online publication 6 January 2015Here, we report a simple and low-cost oral oligodeoxynucleotide (ODN) delivery system targeted to the gut Peyer's patches (PPs). This system requires only Dulbecco's modified eagle's medium, calcium chloride, ODNs, and basic laboratory equipment. ODN nanocapsules (ODNcaps) were directly delivered to the PPs through oral administration and were taken up by macrophages in the PPs, where they induced an immune response. Long-term continuous oral dosing with inhibitory/suppressive ODNcaps (iODNcaps, "iSG3caps" in this study) was evaluated using an atopic dermatitis mouse model to visually monitor disease course. Administration of iSG3caps improved skin lesions and decreased epidermal thickness. Underlying this effect is the ability of iSG3 to bind to and prevent phosphorylation of signal transducer and activator of transcription 6, thereby blocking the interleukin-4 signaling cascade mediated by binding of allergens to type 2 helper T cells. The results of our iSG3cap oral delivery experiments suggest that iSG3 may be useful for treating allergic diseases.ArticleMOLECULAR THERAPY. 23(2):297-309 (2015)journal articl

High Levels of Tetrodotoxin in the Flesh, Usually an Edible Part of the Pufferfish Takifugu flavipterus, Caused by Migration from the Skin and the Regional Characteristics of Toxin Accumulation

The consumption of a pufferfish, Takifugu flavipterus or komonfugu in Japanese, formerly known as Takifugu poecilonotus, is popular in Japan. However, T. flavipterus is frequently involved in cases of tetrodotoxin (TTX) poisoning in Japan. Although victims have usually consumed inedible parts, some cases are related to consumption of flesh. To improve the risk management of pufferfish poisoning, we studied TTX level in the flesh and skin of T. flavipterus. Ninety-seven specimens obtained from the Seto Inland Sea and landed in Fukuoka Prefecture were analyzed by liquid chromatography-tandem mass spectrometry. The flesh from six specimens was toxic (>10 MU/g = 2.2 mg/kg): one was in poor condition (not freeze–thawed); three were freeze–thawed before sample preparation; and two freshly prepared and in good condition (not freeze–thawed). The fillets were divided into outer and inner portions; the TTX levels in the outer portions were notably higher. The skin of the six specimens was moderately to extremely toxic: 165 MU/g (36.3 mg/kg) in the fresh specimen not in good condition, 600–950 MU/g (132–200 mg/kg) in freeze–thawed specimens, and 4500 and 6000 MU/g (990 and 1320 mg/kg) in the two fresh specimens. We concluded that TTX in the flesh migrated from the highly toxic skin. In addition, TTX levels in the skin appeared to be regionally specific. We recommend that toxic portions of T. flavipterus are removed as soon as possible after individuals are caught, and that fish from known highly toxic areas are not consumed

Incidentally found abdominal para-aortic and inferior mesenteric root lymph node metastases of prostatic adenocarcinoma in a surgical case with sigmoid colon cancer

We report a rare case of incidentally found metastatic adenocarcinoma in the abdominal para-aortic and inferior mesenteric root lymph nodes originating from the prostate, at the time of surgery in a patient with sigmoid colon cancer. A man in his mid-seventies was scheduled to undergo laparoscopic-assisted sigmoidectomy and regional lymph node dissection. At the beginning of laparoscopic surgery, a caterpillar-like swelling of abdominal para-aortic lymph nodes was found; the diagnosis using frozen sections was a metastatic adenocarcinoma showing cribriform and solid growth patterns different from typical colorectal cancer. The surgical procedure was changed to an abdominal sigmoidectomy with widely extended lymph node dissection, including inferior mesenteric root lymph nodes and sampling of abdominal para-aortic lymph nodes. The resected sigmoid colon cancer was a papillary/tubular adenocarcinoma invading the muscularis with no lymph node metastasis (pT2N0M0/pStage IIA). Additionally, the presence of a metastatic adenocarcinoma showing cribriform and solid growth patterns different from the primary sigmoid colon cancer was confirmed in the abdominal para-aortic and inferior mesenteric root lymph nodes. The metastatic adenocarcinoma cells were positive for prostate-specific antigen (PSA) and negative for CDX2, indicating that the tumor was from the prostate. A total of ten prostatic core needle biopsy specimens also contained a usual (acinar) adenocarcinoma, with a Gleason score of 4 + 5 = 9. Androgen blockade was performed; the serum PSA level was reduced to 0.06 nanograms per microliter in the subsequent five months. Regardless of radiologic images, examination of serum PSA level is recommended before surgery in male surgical colorectal cancer patients more than 60 years old