Shoplifting Behavior Among Patients With an Eating Disorder at a Medical Correctional Center in Japan: A Cross-Sectional Study.

Purpose: In Japan, the incarceration of patients with eating disorders (EDs) owing to repeated shoplifting has become a social issue. This study examined the shoplifting behavior of inmates with EDs at our medical correctional center, with the objective of delineating their characteristics, identifying an adequate treatment plan, and preventing recidivism. Methods: The participants consisted of 32 incarcerated patients with EDs (22 females, 10 males) charged with shoplifting, from a medical correctional center in East Japan. A cross-sectional study was employed. Data were collected by retrieving the patients' medical records and through individual interviews conducted by psychiatrists. Results: The food-specific shoplifting ED group (those who had never shoplifted anything other than food) had a core pathology of the binge-purge type of anorexia nervosa with juvenile onset (p = 0.044). Furthermore, they demonstrated an average gap of 8 years between the onset of ED and their first shoplifting episode. The non-specific shoplifting ED group (those who shoplifted food and other items) typically shoplifted before the onset of ED (p = 0.001). They experienced the onset of ED after incarceration (p = 0.004) and had comorbid disorders (p = 0.024). The food-specific group required a psychosocial approach focusing on maintaining healthy body weight and mental stability, whereas the non-specific group required multiple forms of support for substance abuse and behavioral addiction, as well as interventions to reduce impulsive behavior. Conclusion: Early intervention is necessary to improve the prognosis of patients with EDs and shoplifting behavior.

[Comparison of the Pharmaceutical Characteristics of Brand-name and Generic Pramipexole Extended-release Tablets and Their PTP Usability].

The pramipexole extended-release (long acting) tablet, a D2 receptor agonist commonly used for the treatment of Parkinson's disease, has increasingly demonstrated usability for patients with long acting performance and patient adherence improvements. As a generic drug it is sold by six companies while a brand name drug is also marketed. As these formulations are hygroscopic it is described as such in package inserts so that tablets will only be removed from the press-through package (PTP) immediately before ingestion. It is often dispensed in one-dose packaging (ODP) as determined by a patient's physical functions and symptom characteristics. With ODP, quality control and ease of removal from the PTP are important factors. In this study we examined the stability of tablets in the ODP (25℃ RH75%) while also comparing the ease of handling of the seven products currently marketed in Japan. In the tablets' ODP, changes such as swelling and decreases in tablets hardness were observed in six formulations. Differences were found among the products in comparison of packaging material, required tablet extrusion strength, and ease of removal. Given the differences in PTP materials and hygroscopicity it is suggested that pharmacists must not only consider the drug formulations of products but also contribute to improvements in medication adherence for patients with poor hand-finger function.

[Quality evaluation for pharmaceutical products and medical supplies: proper use].

  In the proper use of medicine, the quality of medical supplies is an important factor. Use of generic products not only reduces drug costs for the patient, but also offers substantial advantages for governments in reducing medical expenses. When evaluation of the quality of generic products is centered on tablets, products with qualities that are unstable over time may be encountered. Some dosage forms require suitable pharmaceutical tests, processes, and apparatuses, such as those for evaluating orally disintegrating tablets or cutaneous preparations. For example, although simple test equipment has been proposed for patches, a unified method is required. The pharmacist plays an important role in choosing high-quality generic products; however, a substantial amount of information needs to be made available to the public in order to achieve that goal.

[Property of metronidazole film prepared with natural polysaccharides].

Film dosage forms containing metronidazole (MZ) were prepared from natural polysaccharides, such as pullulan (PUL) or sodium alginate (ALG), without heating or controlling the pH. The release profiles of MZ from the films were investigated. In the absence of a drug, the casting method resulted in the polysaccharide forming a circular film, and the presence of MZ affected film formation. The thickness of the film was controllable by adjusting the concentration of ALG, and regular unevenness was observed on the surface of film. The film prepared with PUL or ALG readily swelled in dissolution medium, and released MZ with disintegration. The films prepared from the polysaccharides could be promising candidates as dosage forms containing MZ, and would be expected to show drug dissolution in the surface of skin.

Drug interaction between celecoxib and methotrexate in organic anion transporter 3-transfected renal cells and in rats in vivo.

Methotrexate has a clinically important pharmacokinetic interaction with nonsteroidal anti-inflammatory drugs (NSAIDs) mainly through its competition for tubular secretion via the renal organic anion transporter 3 (OAT3). We have previously reported the usefulness of OAT3-transfected renal tubular cells for screening of the drugs which interfere with the pharmacokinetics of methotrexate. Celecoxib, a cyclooxygenase (COX) 2 inhibitor, has not been reported to interact with methotrexate, but the mechanisms are unclear why the interaction did not occur. The purpose of this study was to evaluate the effect of celecoxib on methotrexate tubular secretion using a renal cell line stably expressing human OAT3 (S2-hOAT3), and to evaluate the pharmacokinetic interaction of the two drugs in rats. [3H]methotrexate uptake into S2-hOAT3 cells was significantly inhibited by celecoxib in a concentration-dependent manner and the Ki value was 35.3 microM. However, methotrexate serum concentrations and urinary excretion of methotrexate over 24 h in rats were not affected by celecoxib (50, 200 mg/kg). Celecoxib serum concentrations were increased by the increase in celecoxib dosage and the maximum drug concentration (Cmax) was 20.6 microM (celecoxib 200 mg/kg), which did not reach the Ki value obtained in the in vitro study. These results indicated that celecoxib inhibited the secretion of methotrexate via hOAT3, which suggested that celecoxib was a substrate of hOAT3. However, co-administration of the two drugs at clinical dosage did not affect the pharmacokinetics of methotrexate, because the serum concentrations did not reach the Ki value. Although the accumulation study using S2-hOAT3 cells was useful to predict the interaction between the new drug and methotrexate in vivo, a comparison of the Ki value with the Cmax in clinical dosage was necessary to evaluate the degree of this interaction.

Edaravone, a free radical scavenger, mitigates both gray and white matter damages after global cerebral ischemia in rats.

Recent studies have shown that similar to cerebral gray matter (mainly composed of neuronal perikarya), white matter (composed of axons and glias) is vulnerable to ischemia. Edaravone, a free radical scavenger, has neuroprotective effects against focal cerebral ischemia even in humans. In this study, we investigated the time course and the severity of both gray and white matter damage following global cerebral ischemia by cardiac arrest, and examined whether edaravone protected the gray and the white matter. Male Sprague-Dawley rats were used. Global cerebral ischemia was induced by 5 min of cardiac arrest and resuscitation (CAR). Edaravone, 3 mg/kg, was administered intravenously either immediately or 60 min after CAR. The morphological damage was assessed by cresyl violet staining. The microtubule-associated protein 2 (a maker of neuronal perikarya and dendrites), the beta amyloid precursor protein (the accumulation of which is a maker of axonal damage), and the ionized calcium binding adaptor molecule 1 (a marker of microglia) were stained for immunohistochemical analysis. Significant neuronal perikaryal damage and marked microglial activation were observed in the hippocampal CA1 region with little axonal damage one week after CAR. Two weeks after CAR, the perikaryal damage and microglial activation were unchanged, but obvious axonal damage occurred. Administration of edaravone 60 min after CAR significantly mitigated the perikaryal damage, the axonal damage, and the microglial activation. Our results show that axonal damage develops slower than perikaryal damage and that edaravone can protect both gray and white matter after CAR in rats.

Evaluation of the interaction between nonsteroidal anti-inflammatory drugs and methotrexate using human organic anion transporter 3-transfected cells.

Coadministration of methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) can cause a pharmacokinetic interaction and a subsequent increase in blood methotrexate concentrations. methotrexate and most NSAIDs are excreted into urine via organic anion transporter 3 (OAT3). The purpose of this study was to evaluate NSAIDs that compete less with methotrexate by using the renal cell line stably expressing human OAT3 (S2-hOAT3) in vitro. We also confirmed the pharmacokinetic interaction of methotrexate with NSAIDs in vivo. [(3)H]methotrexate uptake into S2-hOAT3 cells was inhibited by most NSAIDs in a concentration-dependent manner, but aspirin, salicylate, tiaramide, and acetaminophen did not inhibit uptake. Inhibition by sulindac and pranoprofen was weaker at therapeutic drug concentrations. Furthermore, methotrexate concentrations in rat serum were significantly increased in a NSAID concentration-dependent manner when concentrations of coadministered NSAIDs increased above the Ki values obtained in the in vitro study. On the other hand, drugs that were not substrates of hOAT3, such as acetaminophen, did not interact with methotrexate. The magnitude of the pharmacokinetic interaction between methotrexate and NSAIDs was significantly correlated with results of the accumulation study in vitro and was not significantly correlated with a reduction of urinary creatinine excretion. In conclusion, methotrexate and most NSAIDs are substrates of hOAT3, and those drugs compete via hOAT3 in tubular secretion, the major mechanism of the interaction between methotrexate and NSAIDs. The accumulation study using S2-hOAT3 cells might be useful for screening of potential interactions between methotrexate and new NSAIDs in vivo.

Effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats.

The purpose of this study was to investigate the effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats. The blood concentration-time course and pharmacokinetic parameters of ciclosporin did not significantly change after intravenous injection of ciclosporin (10 mg kg(-1)) in rats treated with imatinib mesilate (50 mg kg(-1)) as compared with a control. When ciclosporin (10 mg kg(-1)) was orally administered, the time course, area under the curve, bioavailability and peak blood concentration of ciclosporin were significantly increased in rats that had been treated with imatinib mesilate 2 h before ciclosporin administration as compared with the control. Because both drugs are transported via P-glycoprotein and breast cancer resistance protein and metabolized by cytochrome P450 3A2, the interaction of imatinib mesilate with these proteins may be responsible for the increased intestinal absorption of ciclosporin in rats. These results indicate that imatinib mesilate enhanced the intestinal absorption of ciclosporin in rats with only the oral administration of ciclosporin, suggesting that our results support clinical data. In addition, imatinib mesilate may increase the pharmacological effects and possibly toxicity of ciclosporin.

Inhibition of theophylline metabolism by suplatast and its metabolites in rats.

The inhibitory effect of suplatast (ST), an anti-allergic drug, on theophylline (TP) metabolism was investigated in rats in vivo and in vitro. Intravenous injection of aminophylline (AP) at 10 mg/kg of TP equivalent was performed with or without pretreatment by oral administration of 100 mg/kg of ST 2.5 h prior to AP. In the ST-pretreated group, plasma concentration (Cp), the area under Cp-time profile (AUC) and urinary excretion of TP increased significantly, and urinary excretion of TP metabolites, 1,3-dimethyluric acid (DMU) and 1-methyluric acid (1MU) decreased significantly. Metabolic clearance of DMU (CL(DMU)) and that of 1MU (CL(1MU)) were remarkably suppressed by ST pretreatment, however, renal clearance (CLr) of TP did not change. To compare the inhibitory effect of ST on TP metabolism with that of its main metabolite (M1) in vivo, a concomitant intravenous injection of AP (10 mg/kg of TP equivalent) with ST or M1 (40 mg/kg of ST equivalent) was carried out. In the M1 group, Cp and AUC of TP increased significantly, and the total body clearance of TP decreased significantly. In contrast, ST did not induce these changes. Then, the inhibitory effect of ST and M1 on TP metabolism in vitro was evaluated using rat-liver microsomes. ST and M1 suppressed DMU formation in a competitively inhibitory manner, and their equilibrium dissociation constants (Ki) were 822 and 731 microM, respectively. In conclusion, inhibition of TP metabolism by ST was demonstrated in vivo and in vitro, and the involvement of M1 and/or other metabolites in this drug interaction was suggested.

Adsorption of bile acid by chitosan-orotic acid salt and its application as an oral preparation.

The orotic acid (OT) salt of chitosan (CS), CS-OT, and that of a CS derivative, CP, were prepared, and the adsorption of primary or secondary bile acid was investigated. Calcium-induced alginate gel beads (Alg-Ca) containing CS-OT were also prepared and autoclaved, and the possibility of these beads to act as a vehicle for oral administration to prevent hyperlipidemia was investigated. When taurocholate (TCA) and glycocholate (GCA) were present together in the medium, CS-OT adsorbed identical amounts of both bile acids. This trend was seen in all CPs, although the capacity to adsorb bile acid was affected by the number and/or structure of the amino groups in the CP. On the other hand, taurodeoxycholate, a secondary bile acid was preferentially adsorbed over TCA and GCA. Alg-Ca containing CS-OT took up bile acids in a similar manner as CS-OT irrespective of the water content of the gel matrix. As all elements can be taken as a food, Alg-Ca containing CS-OT could serve as a useful dietary agent for the prevention of hyperlipidemia, which is a lifestyle-related disease.

Drug release properties of a gel bead prepared with pectin and hydrolysate.

A calcium-induced pectin gel bead (PB) containing pectin hydrolysate was prepared, and the drug release profiles and degradation properties of the PB were investigated in aqueous media. The stiff PB swelled in physiological saline and its drug release rate decreased with exposure to increasing concentrations of CaCl2 during preparation. And erosion of the PB was not observed in physiological saline. However, the PB did disintegrate in phosphate buffer (pH 6.8) and the rate of disintegration depended on the calcium chloride concentration used to prepare the PB. In addition, the drug release rate of the PB in buffer solution decreased as the rate of gel erosion declined. Consequently, it appears that the PB gel matrix is an effective medium by which to control the release of drug within the gastrointestinal tract.

Properties of an alginate gel bead containing a chitosan-drug salt.

A calcium-induced alginate gel bead (Alg-CS) containing chitosan (CS) and 2-(4-chlorophenoxy)-2-methylpropionic acid (CMP) was prepared. We then investigated (a) CMP release from Alg-CS, and (b) uptake of bile acid into the Alg-CS, within the gastrointestinal tract. Dried Alg-CS gradually swelled in taurocholate solution, while releasing CMP and taking up bile acid. The amount of bile acid taken up into the Alg-CS increased incrementally according to the degree of deacetylation of CS. Furthermore, the molecular weight of CS also affected the properties of the Alg-CS. An approximately linear relationship was observed between CMP release and bile acid uptake of Alg-CS.

Ketamine attenuates hypocapnia-induced neuronal damage in the caudoputamen in a rat model of chronic cerebral hypoperfusion.

We previously demonstrated that the caudoputamen was exclusively further damaged by hypocapnia in a rat with chronic cerebral hypoperfusion which is characterized by white matter lesions (WML) and a well-established model for patients with cerebrovascular diseases and/or dementia, and suggest that this process may be the cause of long lasting postoperative delirium or brain dysfunction in such patients. In the present study, we investigated whether ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, could attenuate the neuronal damage in the caudoputamen. Ketamine, at doses of 10 and 20 mg/kg, which was given intraperitoneally before hypocapnia induction, attenuated the aggravation of WML score, neuronal damage, and astroglial proliferation in the rat caudoputamen. These results suggest that ketamine may be beneficial for preventing postoperative brain dysfunction, especially in patients with cerebrovascular diseases and/or dementia induced by hypocapnia, which is likely to occur in the mechanical ventilation used during surgery.

[Anesthesia for laparoscopic cryptorchidpexy in a patient with congenital myopathy].

A relatively high incidence of malignant hyperthermia (MH) and an unpredicted (usually increased) sensitivity to muscle relaxants are reported in patients with congenital myopathies (CM). We present a case of anesthetic management of a patient with a clinical diagnosis of CM. An 18-month-old, 11.3-kg, male patient, who had received a diagnosis of CM, was scheduled for the laparoscopic cryptorchidpexy. Anesthesia was induced with propofol and fentanyl, and the trachea was intubated without muscle relaxants. An epidural catheter was inserted via the sacral hiatus, the tip of which was located at the second lumbar level for a purpose of obtaining not only pain relief but also muscle relaxation. Anesthesia was maintained with propofol, nitrous oxide and fentanyl, combined with epidural anesthesia. The anesthetic course was uneventful with enough pain relief and good muscle relaxation.

[NMDA receptor antagonist neurotoxicity and psychotomimetic activity].

Non-competitive NMDA receptor antagonists, in spite of their neuroprotective effects against neuronal ischemia, brain trauma, etc., cause neuronal damage in the rodent posterior cingulate and retrosplenial cortices (PC/RS), which are thought to be responsible brain regions for their psychotomimetic activity in humans. A number of anesthetics have not only GABAA receptor activating properties but also NMDA receptor antagonist properties. On the other hand, ketamine and nitrous oxide, both of which are potent non-competitive NMDA receptor antagonists and have little GABAA activating properties, are demonstrated to induce neuronal damage in the rat PC/RS. Furthermore, ketamine potentiates the neuronal damage by nitrous oxide. Although many anesthetics, such as halothane, isoflurane, barbiturates and benzodiazepines, inhibit the neuronal damage in the PC/RS by NMDA receptor antagonists, probably through GABAA receptor activation, we anesthesiologists should be aware of the risk of ketamine or nitrous oxide anesthesia, not to speak of the combined use of them, without using GABAA receptor activating agents.

Pentobarbital inhibits ketamine-induced dopamine release in the rat nucleus accumbens: a microdialysis study.

UNLABELLED: Dopamine release in the nucleus accumbens (NAC) plays a crucial role in the actions of various psychotropic and addictive drugs. Ketamine and barbiturates have psychotropic effects and addictive properties, but barbiturates prevent ketamine's psychotomimetic effects. We investigated the effects of ketamine and pentobarbital on dopamine release in the NAC. A microdialysis probe was implanted in the NAC in 35 rats, which were randomly assigned to seven groups: a normal saline intraperitoneal injection (ip) group, 50 and 100 mg/kg of ketamine ip groups, 25 and 50 mg/kg of pentobarbital ip groups, and a normal saline or 25 mg/kg of pentobarbital ip followed by 50 mg/kg of ketamine ip groups. Perfusate samples were collected every 20 min, and dopamine concentration was measured by high-performance liquid chromatography. Ketamine at doses of 50 mg/kg and 100 mg/kg significantly increased dopamine release in the NAC. Conversely, pentobarbital significantly decreased dopamine release in the NAC and inhibited the ketamine-induced dopamine release. These data suggest that the dopamine release in the NAC may be involved in ketamine-induced, but not barbiturate-induced, psychotropic effects and addiction. Inhibition of ketamine-induced dopamine release by barbiturates may be a mechanism by which they prevent ketamine emergence reactions. IMPLICATIONS: Ketamine increased dopamine release in the nucleus accumbens, which was inhibited by pentobarbital. The mesolimbic dopamine system may be involved in the psychotomimetic effects of ketamine, and the suppression of ketamine emergence reactions by barbiturates may be because of the inhibition of ketamine-induced dopamine release in the nucleus accumbens.

Ketamine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices is mediated not only via NMDA receptors but also via sigma receptors.

Ketamine induces marked c-fos expression in the posterior cingulate and retrosplenial cortices (PC/RS). We investigated whether NMDA and/or sigma receptors were involved in the c-Fos expression. The number of Fos-LI positive boutons in NMDA receptor knockout mice was significantly lower than that in wild-type mice. Rimcazole but not haloperidol significantly suppressed the c-Fos expression. The results indicate that the ketamine-induced c-Fos expression is mediated not only via NMDA receptors but also via sigma receptors.

Anticonvulsant effects of sevoflurane on amygdaloid kindling and bicuculline-induced seizures in cats: comparison with isoflurane and halothane.

PURPOSE: We compared the anticonvulsant effects of sevoflurane with those of isoflurane and halothane in amygdaloid kindling and bicuculline-induced seizures in cats. METHODS: In a crossover design, the effects of 70% nitrous oxide, and 0.3, 0.6, and 1.5 minimum alveolar concentration (MAC) of volatile anesthetics were studied in five cats in which the amygdala was electrically stimulated at the current used for establishing the kindled state. The effects of 0.6 and 1.5 MAC of volatile anesthetics were studied in another five cats, in which 0.2 mg.kg(-1) of bicuculline was administered i.v.. RESULTS: In the amygdaloid kindling model, all four anesthetics decreased the duration of after-discharge (AD), the rise of multiunit activity in midbrain reticular formation (R-MUA), and the behavior scores compared with findings without anesthetics. Halothane, at 1.5 MAC, significantly decreased the number of cats showing AD ( P < 0.05). In the bicuculline-induced seizure model, all five cats showed repetitive spikes during 1.5 MAC of sevoflurane, whereas only two and three cats, respectively, showed the repetitive spikes during 1.5 MAC of isoflurane and halothane. All three volatile anesthetics decreased the rise of R-MUA, the duration of the repetitive spikes, and the behavior scores. The suppression of the rise in R-MUA and the behavior scores with 1.5 MAC of sevoflurane was significantly less than that with 1.5 MAC of isoflurane. CONCLUSION: The anticonvulsant effects of sevoflurane were less potent than those of halothane in the amygdaloid kindling model and less potent than those of isoflurane in the bicuculline-induced seizure model.