Co-Occurrence of Tetrodotoxin and Saxitoxins and Their Intra-Body Distribution in the Pufferfish Canthigaster valentini.

Pufferfish of the family Tetraodontidae possess tetrodotoxin (TTX) and/or saxitoxins (STXs), but the toxin ratio differs, depending on the genus or species. In the present study, to clarify the distribution profile of TTX and STXs in Tetraodontidae, we investigated the composition and intra-body distribution of the toxins in Canthigaster valentini. C. valentini specimens (four male and six female) were collected from Amami-Oshima Island, Kagoshima Prefecture, Japan, and the toxins were extracted from the muscle, liver, intestine, gallbladder, gonads, and skin. Analysis of the extracts for TTX by liquid chromatography tandem mass spectrometry and of STXs by high-performance liquid chromatography with post-column fluorescence derivatization revealed TTX, as well as a large amount of STXs, with neoSTX as the main component and dicarbamoylSTX and STX itself as minor components, in the skin and ovary. The toxins were also detected in the other tissues, but in much lower amounts than in the skin and ovary. The TTX/STX ratio varied greatly, depending on the tissue, but TTX was the major toxin component in the whole body, and STXs accounted for 25% and 13% of the total toxin amount in males and females, respectively. Like the marine pufferfish of the genus Arothron, C. valentini should be considered a pufferfish with considerable amounts of both TTX and STXs present simultaneously.

Evaluation of the tetrodotoxin uptake ability of pufferfish Takifugu rubripes tissues according to age using an in vitro tissue slice incubation method.

The tetrodotoxin (TTX) uptake ability of pufferfish Takifugu rubripes tissues and its growth-associated changes were investigated using an in vitro tissue slice incubation method. Tissue slices prepared from the liver, skin, and intestine of a non-toxic cultured adult T. rubripes (20 months old) and incubated with incubation buffer containing 25 µg/mL TTX for 1-48 h showed a time-dependent increase in the TTX content in all tissues. The TTX contents of the skin and intestine slices were comparable to or slightly higher than that of the liver slices, with a similar transition pattern, suggesting similar TTX uptake ability among the skin, intestine, and liver. The TTX uptake ability of the liver and intestine did not differ significantly between young (8 months old) and adult (20 months old) fish, but the skin slices of young fish took up approximately twice as much TTX as that of adult fish, suggesting that the TTX uptake ability of the skin is involved in the growth-dependent changes in the toxin distribution inside the body in T. rubripes. To estimate the TTX uptake pathway in each tissue, an immunohistochemical technique was used to observe temporal changes in the intra-tissue microdistribution of TTX during incubation. The findings suggested that TTX is transferred and accumulates from pancreatic exocrine cells to hepatic parenchymal cells in the liver, from connective tissues to basal cells in the skin, and from villi epithelial cells via the lamina propria to the muscle layer in the intestine.

Contrasting Toxin Selectivity between the Marine Pufferfish Takifugu pardalis and the Freshwater Pufferfish Pao suvattii.

To clarify the differences in toxin selectivity between marine and freshwater pufferfish, we conducted experiments in artificially reared nontoxic specimens of Takifugu pardalis (marine) and Pao suvattii (freshwater) using tetrodotoxin (TTX) and paralytic shellfish poison (PSP; decarbamoylsaxitoxin (dcSTX) or saxitoxin (STX)). T. pardalis specimens were administered feed homogenate containing TTX or dcSTX (dose of toxin, 55.2 nmol/fish) and P. suvattii specimens were administered feed homogenate containing TTX + STX (dose of each toxin, 19.2 nmol/fish) by oral gavage. The toxin content in the intestine, muscle, skin, liver, and gonads was quantified after 24 and 48 or 72 h. In T. pardalis, TTX administered into the intestine was absorbed into the body and transferred and retained mainly in the skin and liver, while dcSTX was hardly retained in the body, although it partly remained in the intestine. In strong contrast, in P. suvattii, little TTX remained in the body, whereas STX was absorbed into the body and was transferred and retained in the ovary and skin. The findings revealed that TTX/PSP selectivity differs between the marine species T. pardalis and the freshwater species P. suvattii. T. pardalis, which naturally harbors TTX, selectively accumulates TTX, and P. suvattii, which naturally harbors PSP, selectively accumulates PSP.

[Efficacy of the Serigaya Methamphetamine Relapse Prevention Program (SMARPP): for patients with drug use disorder: A study on factors influencing 1-year follow-up outcomes].

PURPOSE: The purpose of this study was to evaluate the efficacy of the Serigaya Methamphetamine Relapse Prevention Program (SMARPP), which is the workbook-based group therapy for individuals with drug dependence, through investigating 1-year follow-up outcomes. METHOD AND SUBJECTS: The sample was drawn from 231 outpatients diagnosed as DSM-IV substance use disorder, who had firstly consulted the drug dependence clinic of the Center Hospital, National Center of Neurology and Psychiatry between September 2009 and June 2013. Of the 231 potential subjects, 79 had participated in SMARPP at least once, and finally 37 who had continued contact this clinic for more than 1 year after due-day of finishing the first SMARPP course were determined as the subjects. We collected the outcome information retrospectively based on clinical records. RESULT: At the 1-year follow-up point, 67.6% of the subjects had continued abstinent at least for a month, and 60% of them had continued full-abstinent for more than 1 year. One of the factors which influenced their abstinence was "having no experience of using new psychoactive substances" (p = 0.029). As for 70.3% of subjects, drug-use frequency decreased and the only factor for their improvement was "participating in SMARPP many times" (p = 0.040). Of the subjects, 23 patients corresponded to methamphetamine use disorder, and 65.2% of them had continued abstinent at least for a month at the 1-year follow-up point. Additionally, 60% of them had continued full-abstinent for more than 1 year. DISCUSSION AND CONCLUSION: Our study demonstrated possible effectiveness of SMARPP for patients with drug use disorder, especially methamphetamine-use-disorder. The factors of abstinence or decrease of drug-use frequency may be to participate in SMARPP many times, not to abuse "not illegal" drugs such as new psychoactive substances or hypnotics/anxiolytics and to continue treatment for more than 1 year after due-day of finishing the program.

[Long-standing overt ventriculomegaly in adults (LOVA) needing ventriculo-peritoneal shunt with double programmable pressure valves].

A 44-year-old man presented with symptomatic hydrocephalus due to aqueductal stenosis. Endoscopic third ventriculostomy was performed but proved ineffective, so ventriculo-peritoneal shunt using a programmable pressure valve (PPV) was carried out. Subdural hematoma appeared 5 weeks postoperatively and subsequently increased though the pressure setting was maximum. One more valve was implanted in the right chest wall and drainage of the hematoma was performed 2 months after the shunt operation. Adjustment of pressure was repeated. Findings of overdrainage and underdrainage were seen once each afterwards. We followed up the patient with the first valve set at 200 mm H2O and the second valve set at 60 mm H2O. Disturbance of memorization improved. The patient was in a stable condition 10 months after the final pressure settings. Flow volume changes were examined under conditions of various pressures in tandemly connected double programmable valves in vitro. When total pressure increased, flow showed a linear decrease that was not associated with the order of the pressure settings. This method of adding one more PPV was effective, and appears to be a useful choice for treating overdrainage.