[Clinical analysis of 30 cases of Castleman disease with different types of thoracic involvement].

Objective: To improve the clinical understanding of Castleman disease (CD) with different types of thoracic involvement, including their clinical features, radiological and pathological findings, diagnosis and current treatment strategies. Methods: Retrospective analysis of 30 patients diagnosed with CD with thoracic involvement and hospitalized between June 2009 and May 2019 in The First Affiliated Hospital of Guangzhou Medical University was performed. Patients were divided into three groups for subsequent analysis based on the clinical data: CD with bronchiolitis obliterans (BO) , unicentric Castleman disease (UCD) without BO, and multicentric Castleman disease (MCD) without BO. Results: Among the 30 patients, there were 5 (16.7%) patients diagnosed with BO, 18 (60.0%) patients had UCD without BO and 7 (23.3%) patients had MCD without BO. The average age of MCD without BO patients was significantly older than that of BO and UCD without BO patients[ (49.29±5.39) ys vs (27.20±3.76) ys and (37.17±2.87) ys; P=0.005 and 0.034, respectively) ]. Pulmonary symptoms were commonly seen in BO group (100%) and MCD without BO group (71.4%) . while no pulmonary symptoms were seen in UCD without BO group. Key abnormal laboratory findings were erythrocyte sedimentation rate (ESR) increase (40%in BO group and 57.1% in MCD without BO group) and hypoxia (60% in BO group and 28.6% in MCD without BO group) . Other abnormal laboratory findings seen in MCD without BO group included anemia and IgG increase (both 57.1%) . Notably, all patients in BO group had extremely severe mixed ventilation dysfunction in the lung function test. CT scan showed lung parenchyma involvement in BO group (100%) , in UCD without BO group (11.1%) featured by solitary pulmonary nodule and in MCD without BO group (57.1%) featured by diffuse lesions in bilateral lungs. The size of lymph nodes was significantly smaller in MCD without BO group comparing to that in BO group and UCD without BO group[short diameter (1.83±0.51) cm vs (4.73±1.63) cm and (3.62±0.26) cm; P=0.006 and 0.011, respectively]. All patients (100%) in the BO group had a pathological type of transparent vascular variant while the same pathological type accounts for 88.9% in UCD without BO patients. The predominantly pathological type (57.1%) was plasma cell variant in the MCD without BO group. Oral ulcers presented in all patients in BO group but were relieved after the mass resection and immunomodulatory therapy, but the pulmonary symptoms were still progressively aggravated. Thoracoscopic mass excision was the main treatment for UCD without BO patients while chemotherapy, immunomodulatory and targeted therapy were commonly used for MCD without BO treatment. Conclusion: The age, clinical symptom, laboratory finding, lung function, imaging manifestation, pathology, treatment and prognosis were different among the three groups. This classification could improve clinical understanding of the disease.

Binge-like acquisition of 3,4-methylenedioxypyrovalerone (MDPV) self-administration and wheel activity in rats.

RATIONALE: Lack of access to conventional sources of reinforcement has been proposed as a risk factor for substance abuse in lower socioeconomic populations. There is laboratory evidence that behavioral alternatives (enrichment or exercise) and alternative reinforcers (e.g., sweetened solutions) can reduce self-administration of a variety of drugs. OBJECTIVES: The objective of this study is to determine if drug self-administration could devalue wheel activity in an animal model. METHODS: Male Wistar rats were trained to self-administer 3,4-methylenedioxypyrovalerone (MDPV; "bath salts"), 0.05 mg/kg/infusion, i.v., with concurrent access to a running wheel that was either locked (LW) or unlocked (UW). RESULTS: MDPV intake steadily increased across the 20-session acquisition interval but did not differ significantly between UW and LW groups. Mean wheel rotations declined significantly across the acquisition interval in the UW group. Of the rats that acquired self-administration, 60 % engaged in a binge-like behavior at the initiation of acquisition; intake was limited only by post-reinforcement time-out. The binge rats had higher post-acquisition levels of drug intake (even after excluding the binge session), and the UW binge rats showed a precipitous post-acquisition drop in wheel activity that was not observed in the UW no-binge rats. CONCLUSIONS: These data confirm that MDPV is a powerful reward/reinforcer and show that a relatively high rate of intake at the onset of drug taking can devalue natural rewards (wheel activity) and can predict higher subsequent drug intake levels. Thus, limiting the intensity of initial drug exposure may attenuate subsequent drug abuse/addiction by preventing the devaluation of natural alternative rewards/reinforcers.

Synthetic (+)-antroquinonol exhibits dual actions against insulin resistance by triggering AMP kinase and inhibiting dipeptidyl peptidase IV activities.

BACKGROUND AND PURPOSE: The fungal product (+)-antroquinonol activates AMP kinase (AMPK) activity in cancer cell lines. The present study was conducted to examine whether chemically synthesized (+)-antroquinonol exhibited beneficial metabolic effects in insulin-resistant states by activating AMPK and inhibiting dipeptidyl peptidase IV (DPP IV) activity. EXPERIMENTAL APPROACH: Effects of (+)-antroquinonol on DPP IV activity were measured with a DPPIV Assay Kit and effects on GLP-1-induced PKA were measured in AR42J cells. Translocation of the glucose transporter 4, GLUT4, induced either by insulin-dependent PI3K/AKT signalling or by insulin-independent AMPK activation, was assayed in differentiated myotubes. Glucose uptake and GLUT4 translocation were assayed in L6 myocytes. Mice with diet-induced obesity were used to assess effects of acute and chronic treatment with (+)-antroquinonol on glycaemic control in vivo. KEY RESULTS: The results showed that of (+)-antroquinonol (100 µM ) inhibited the DPP IV activity as effectively as the clinically used inhibitor, sitagliptin. The phosphorylation of AMPK Thr(172) in differentiated myotubes was significantly increased by (+)-antroquinonol. In cells simultaneously treated with S961 (insulin receptor antagonist), insulin and (+)-antroquinonol, the combination of (+)-antroquinonol plus insulin still increased both GLUT4 translocation and glucose uptake. Further, (+)-antroquinonol and sitagliptin reduced blood glucose, when given acutely or chronically to DIO mice. CONCLUSIONS AND IMPLICATIONS: Chemically synthesized (+)-antroquinonol exhibits dual effects to ameliorate insulin resistance, by increasing AMPK activity and GLUT4 translocation, along with inhibiting DPP IV activity.

The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: self-administration and locomotor activity in rats.

Recreational use of the cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV; "bath salts") has increased worldwide in past years, accompanied by accounts of health and legal problems in the popular media and efforts to criminalize possession in numerous jurisdictions. Minimal information exists on the effects of MDPV in laboratory models. This study determined the effects of MDPV, alongside those of the better studied stimulant d-methamphetamine (METH), using rodent models of intravenous self-administration (IVSA), thermoregulation and locomotor activity. Male Wistar rats were trained to self-administer MDPV or METH (0.05 mg/kg/infusion, i.v.) or were prepared with radiotelemetry implants for the assessment of body temperature and activity responses to MDPV or METH (0-5.6 mg/kg s.c.). METH and MDPV were consistently self-administered within 10 training sessions (mg/kg/h; METH Mean = 0.4 and Max = 1.15; MDPV Mean = 0.9 and Max = 5.8). Dose-substitution studies demonstrated that behavior was sensitive to dose for both drugs, but MDPV (0.01-0.50 mg/kg/inf) showed greater potency and efficacy than METH (0.1-0.25 mg/kg/inf). In addition, both MDPV and METH increased locomotor activity at lower doses (0.5-1.0 mg/kg, s.c.) and transiently decreased activity at the highest dose (5.6 mg/kg, s.c.). Body temperature increased monotonically with increasing doses of METH but MDPV had a negligible effect on temperature. Stereotypy was associated with relatively high self-administered cumulative doses of MDPV (∼1.5 mg/kg/h) as well as with non-contingent MDPV administration wherein the intensity and duration of stereotypy increased as MDPV dose increased. Thus, MDPV poses a substantial threat for compulsive use that is potentially greater than that for METH.