Lasting increase in D1 dopamine receptors in the lateral part of the substantia nigra pars reticulata after subchronic methamphetamine administration

To examine the possible involvement of D₁ dopamine receptors in behavioral sensitization induced by subchronic methamphetamine (MAP) administration, regional D₁ receptors labeled with [³H]SCH 23390 were examined using binding assay and quantitative autoradiography. Rats received 4 mg/kg/day MAP (i.p.) for 14 days, and were decapitated after an abstinence period of 24 h, 7 days or 21 days. In MAP-treated rats, a significant decrease in K_d in the mesolimbic area was observed 24 h but not 7 days after the last injection. Neither K_d nor B_max changed in the striatum or medial prefrontal cortex of MAP-treated rats after any period of abstinence. Autoradiography revealed a significant increase in specific [³H]SCH 22390 binding in the lateral part of the substantia nigra pars reticulata (SNr) of MAP-treated rats. Since this increase lasted up to 21 days after cessation of subchronic MAP administration, it is suggested that lasting increase in the nigral D₁ receptors may be associated with the biological changes underlying MAP-induced behavioral sensitization.     

Successful treatment of refractory enteropathy-associated T-cell lymphoma using high-dose chemotherapy and autologous stem cell transplantation

A 65-year-old woman presented with a 6-month history of abdominal pain and watery diarrhea. Type II enteropathy-associated T-cell lymphoma (EATL) was diagnosed based on the clinical presentation and pathological examination of the tumor. The patient received combination chemotherapy but did not achieve remission. Subsequently, high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) were performed. After these therapies, she achieved complete remission, which has been sustained for 18 months. Although the role of HDT-ASCT for EATL is still controversial, the clinical course of this patient suggests that ASCT can improve the prognosis in some patients with EATL.     

CFTR-deficiency renders mice highly susceptible to cutaneous symptoms during mite infestation

Pruritus, also known as itch, is a sensation that causes a desire to scratch. Prolonged scratching exacerbates skin lesions in several skin diseases such as atopic dermatitis. Here, we identify the cystic fibrosis transmembrane conductance regulator (CFTR/Cftr), an integral membrane protein that mediates transepithelial chloride transport, as a determinant factor in mice for the susceptibility to several cutaneous symptoms during mite infestation. Mice that endogenously express dysfunctional Cftr (Cftr(ΔF508/ΔF508)) show significant increase of scratching behavior and skin fibrosis after mite exposure. These phenotypes were due to the increased expression of nerve growth factor (NGF) that augments the sensitization of peripheral nerve fibers. Moreover, protein gene product 9.5 (PGP9.5)-positive neurites were abundant in the epidermis of mite-infested Cftr(ΔF508/ΔF508) mice. Furthermore, mite-infested Cftr(+/+) mice orally administered with a chloride channel inhibitor glibenclamide had higher scratching count and increased level of NGF than vehicle-treated mice. Consistently, mite extract-exposed primary and transformed human keratinocytes, treated with CFTR inhibitor, had significantly higher level of NGF mRNA compared with vehicle-treated, mite extract-exposed cells. These results reveal that CFTR in keratinocytes plays a critical role for the regulation of peripheral nerve function and pruritus sensation, and suggest that Cftr(ΔF508/ΔF508) mice may serve as a novel mouse model that represents NGF-dependent generation of pruritus.     

Is the surgical stress associated with worse survival in patients with esophageal cancer?--Analysis of colon substitution for 37 patients with remnant stomach

BACKGROUND/AIMS: Colon substitution is a standard method of reconstruction, although an aggressive surgery, for patients with esophageal carcinoma who have remnant stomach. Presence of postoperative complication was reported to be a risk factor for worse survival in the patients with esophageal cancer. We evaluated the affect of this surgical stress on the postoperative course and long-term survival of patients with esophageal carcinoma. METHODOLOGY: Between 1980 and 2002, a total of 37 patients with primary thoracic esophageal squamous cell carcinoma, who had history of gastrectomy due to gastric ulcer, underwent R0 esophagectomy followed by colon substitution (colon group). The clinical affect of colon substitution was retrospectively evaluated in comparison with gastric substitution as the control group (stomach group). RESULTS: The postoperative hospital morbidity rate was significantly higher in the patients with remnant stomach than in the control group. Although the clinicopathological features in both groups were similar, except operative time and bleeding volume, the overall and cause-specific survival of the remnant stomach group were significantly worse than those of the control group. Multivariate analysis suggested that remnant stomach was an independent risk factor for a worse survival. CONCLUSIONS: Surgical stress and postoperative complications, resulted by colon substitution for the patients with remnant stomach, might be associated with worse survival of patients with esophageal cancer.     

Subchondral insufficiency fracture of the femoral head in younger adults

We report two cases of subchondral insufficiency fracture of the femoral head observed in younger adults without any history of overexertion. In both cases, MRI revealed an irregular, discontinuous low-intensity band on the T1-weighted images. Both patients were treated operatively, and histological examination confirmed the diagnosis of subchondral fracture. A diagnosis of subchondral insufficiency fracture needs to be put in as one of the diagnoses in younger patients with a hip pain.     

In situ cross-linkable hyaluronan hydrogels containing polymeric nanoparticles for preventing postsurgical adhesions

OBJECTIVE: To develop a combined barrier method and drug delivery system ("hybrid system") for preventing postoperative peritoneal adhesions, which could combine the biocompatibility and ease of application of in situ cross-linkable hydrogels with the controlled release features of polymeric nanoparticles. METHODS: Poly(lactic-co-glycolic acid) nanoparticles were dispersed in aldehyde- and hydrazide-modified hyaluronic acids (HA), then combined via a double-barreled syringe. The material was subjected to mechanical testing and was assayed for in vitro cytotoxicity to murine mesothelial cells. Subsequently, it was tested for biocompatibility by intraperitoneal injection in mice. The hybrid's effectiveness in preventing postsurgical adhesions was assessed using a rabbit sidewall defect-cecum abrasion model, where it was applied to both injured surfaces. RESULTS: The in situ hybrid gel system formed a flexible and durable hydrogel in less than 10 seconds. It had low in vitro cytotoxicity. In the mouse, the cross-linked HA maintained the polymeric nanoparticles in the peritoneum for 1 week, which we had previously shown would have cleared in less than 2 days, and no animals developed adhesions. Notably, the hybrid gel, even in the absence of encapsulated drug, was highly effective in preventing peritoneal adhesions in the rabbit model employed. Animals treated with the hybrid (n = 8) had no adhesions in 62.5% of cases, and none had adhesions that could only be separated by sharp dissection. In contrast, only 4.2% of untreated animals (n = 24) had no adhesions, and 58.3% developed adhesions requiring sharp dissection. CONCLUSIONS: The hybrid cross-linked HA-nanoparticle system described here appears to be a biocompatible and highly effective adhesion barrier, which could also deliver antiadhesion drugs.