Metabolic effects of D-psicose in rats: studies on faecal and urinary excretion and caecal fermentation

D-psicose (D -ribo-2-hexulose), a C-3 epimer of D-fructose, is one of the "rare sugars" present in small quantities in commercial carbohydrate complex or agricultural products. We investigated the absorption and excretion of D-psicose when orally administrated (5g/kg body weight) to Wistar rats, and the fermentation of D-psicose was measured as caecal short-chain fatty acids (SCFAs) when fed to rats in controlled diets (0, 10, 20 and 30%). Urinary and faecal excretions of D-psicose over the 24 h, following a single oral administration, were 11-15% of dosage for the former and 8-13% of dosage for the latter. Serum D-psicose concentration and D-psicose in the contents of stomach and small intestines decreased progressively after administration. D-psicose in caecum contents was detected after 3h and 7h administration, but not after 1h. Rats fed on D-psicose diets showed short-chain fatty acid production with caecal hypertrophy. These results suggest that D-psicose is partly absorbable in the digestive tract and is excreted into urine and faeces. As with other poorly absorbed dietary carbohydrates, D-psicose is fermented in the caecum by intestinal microflora.     

Vascular endothelial growth factor (VEGF-A) plasma levels in non-small cell lung cancer: relationship with coagulation and platelet activation markers

Platelet activation, commonly found in lung cancer patients, may cause the release of angiogenic factors, such as vascular endothelial growth factor (VEGF-A). The present study was designed to investigate whether plasma VEGF-A levels were associated to different stages of non-small cell lung cancer (NSCLC). Moreover, sP-selectin, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex (TATc) and D-dimer levels were measured to test the hypothesis of an involvement of platelet and coagulation activation in tumor angiogenesis. VEGF-A, sP-selectin, F1+2, TATc and D-dimer levels were elevated in 65 patients with NSCLC, particularly in metastatic patients. sP-selectin (p <0.003) and F1+2 (p <0.005) levels were independently associated to VEGF-A. In addition, patients with positive levels of both sP-selectin and F1+2 had the highest levels of VEGF-A. In conclusion, our findings support the hypothesis that thrombin generation might induce platelet activation and VEGF-A release in NSCLC.     

Practical problems and management of seating through the clinical stages of Duchenne's muscular dystrophy

OBJECTIVE: To describe seating problems in patients with Duchenne's muscular dystrophy (DMD), for the purpose of identifying management solutions that are practicable for both patient and caregiver. DESIGN: Case series. SETTING: A Japanese long-term care facility. PARTICIPANTS: Ninety-five patients with DMD (mean age, 15.9+/-4.4y; Swinyard stages: stage 5, n=17; stage 6, n=24; stage 7, n=33; stage 8, n=21). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Spinal deformity types, frequency and sites of pain, wheelchair propulsive ability, activities of daily living, and caregiving-related problems. RESULTS: Thirty-three percent of the patients belonged to the early straight group, 21% to the scoliotic group, 20% to the kyphoscoliotic group, 2% to the kyphotic group, and 24% to the extended spine group. The percentage needing support for sitting was higher in patients with spinal deformities (76% vs 0%, P<.05). Forty-one percent had pressure problems, and the percentage increased with advancing stages, with pain sites related to spinal deformity types. Self-feeding was difficult in 10 patients having spinal deformities. Four patterns of manual wheelchair propulsion were observed: upper extremity, anteroposterior trunk flexion, lateral trunk flexion, and wrist-hand patterns; and propulsion became increasingly less practical in this order. For toileting, more patients were cared for on wheelchairs with backrests reclined with stage progression. Of 60 caregivers, 58% experienced trauma related to seating systems. CONCLUSION: The seating problems that were identified enabled specific, practical suggestions to be made for better management.     

Pulmonary metastasectomy: might the type of resection affect survival?

BACKGROUND AND OBJECTIVES: Metastasectomy proved to be the choice treatment in the case of pulmonary metastasis. In this study we assessed the impact on survival of three types of resection: minimal by laser or conventional device and lobectomy. METHODS: We considered 85 patients who underwent lung metastasectomy for tumors that originated from various sites. Fifty-two minimal resections were accomplished in 34 patients by conventional (diathermy dissection or stapler suture line) device, 59 resections in 29 by Nd:YAG laser. Lobectomies were 22. Minimum follow up required was 2 years. RESULTS: The 3-year Kaplan-Meier survival rate was 63%, 44%, 53% for laser, conventional resections and lobectomy. The 5-year survival was 40%, 28%, 26% respectively. Among the groups there was no significant difference (P = 0.15). Laser patients showed shorter periods of air leakage and hospital stay. CONCLUSIONS: The type of resection did not disclose statistically significant differences on survival. Minimal surgery, especially by laser device, is recommended for less morbidity.     

The RFG oligomerization domain mediates kinase activation and re-localization of the RET/PTC3 oncoprotein to the plasma membrane

The RET/PTC3 oncogene arises from the fusion between the N-terminal encoding domain of the RFG gene and the tyrosine kinase encoding domain of RET receptor. RET/PTC3 is very frequent in papillary thyroid carcinomas, especially in children exposed to the Chernobyl accident. We have studied the functional consequences of the RFG-RET fusion. Here we show that the N-terminal coiled-coil domain of RGF mediates oligomerization and activation of the kinase and of the transforming capability of RET/PTC3. In addition, the RFG coiled-coil domain mediates a physical association between RET/PTC3 and RGF proteins, rendering RFG a bona fide substrate of RET/PTC3 kinase. Finally, we show that the coiled-coil domain of RGF is essential for the distribution of the RET/PTC3 protein at the membrane/particulate cell compartment level, where also most of the RFG protein is localized. We propose that fusion to the RFG coiled-coil domain provides RET kinase with a scaffold that mediates oligomerization and re-localization of the RET/PTC3 protein, a process that may be crucial for the signalling of this specific RET/PTC variant.     

T cell acute lymphoblastic leukemia arising from familial platelet disorder

Familial platelet disorder (FPD) is a rare autosomal dominant disorder which causes moderate thrombocytopenia with or without impaired platelet function. Patients have a propensity to develop acute myeloid leukemia (AML), and various types of second hits have been postulated in the evolution to AML. However, only a few cases of acute lymphoblastic leukemia (ALL) have been reported thus far. Here, we report a family of FPD with a germ-line hemi-allelic mutation R174X in the RUNX1 gene. The proband of the family developed AML and her son had ALL of the T cell lineage. The balanced translocation t(1;7)(p34.1;q22) was detected in the lymphoblasts from the patient with ALL. This translocation was not seen in any other affected members of the family or in the bone marrow sample of this patient in complete remission. Taken together, t(1;7)(p34.1;q22) is thought to be one of the somatic second hits that predisposes FPD to acute leukemia with T cell phenotype.     

Characteristics of polyarthritis in rabbits by hyperimmunization with attenuated Enterococcus faecalis.

To produce polyarthritis and rheumatoid factor like substance (RFLS), rabbits were hyperimmunized intravenously with 0.02% thimelosal (TMS)-treated Enterococcus faecalis (E. faecalis) as a persistent bacterial flora. Swelling of knee joints occurred at a rate of 41% (27/66), and of shoulder joints at a rate of 25% (17/66) while that of elbow joints occurred at a rate of 4.5% (3/66). On culturing of knee joint fluids, no colonies appeared while 2/4 fluid specimens from the shoulder joints gave positive colonies for 78 days after the first immunization; thereafter, no colonies appeared. On histological examination, in early stages, acute inflammatory reactions with degenerative changes of synovial tissue was observed. In later stages, chronic inflammatory changes, proliferation of synovial cells with pannus formation, destruction of articular cartilage and subchondral bone were observed. RFLS titer showed bi-phasic peaks at 11 days and 41 days after the first immunization. A high incidence of polyarthritis, particularly knee joints, occurred. Thus, hyperimmunization with attenuated E. faecalis as a normal intestinal flora may provide an animal model of chronic polyarthritis.     

Modifying Effect of Folinic Acid on Methotrexate-induced Embryotoxicity in Rats

Abstract Embryotoxicity of methotrexate (MTX) and modification of its effect by folinic acid (FA) were evaluated in rats. MTX was administered intraperitoneally to pregnant rats on day 9 of gestation (vaginal plug = day 0), and was followed by an intraperitoneal injection of FA after various time intervals (0-8 hours). Two dose combinations were used; 0.3 mg/kg of MTX and 1.0 mg/kg of FA, and 3.0 mg/kg of MTX and 10.0 mg/kg of FA. The dams were sacrificed on day 20 of gestation, and the fetuses were examined for visceral and skeletal development. The results are as follows: 1) A single dose of 0.3 mg/kg of MTX resulted in high embryolethality and growth retardation in all live fetuses and a single dose of 3.0 mg/kg of MTX showed 100% embryolethality. 2) A single dose of 1.0 or 10.0 mg/kg of FA showed no embryotoxicity. 3) The mitigating effect of FA on MTX-induced embryotoxicity was observed when FA was administered simultaneously with MTX, but was rapidly decreased as the time interval between MTX and FA dosings became longer. 4) Some live fetuses which escaped from MTX embryolethality showed growth retardation and dilation of the cerebral ventricles. The dilation of the cerebral ventricles was found even in the simultaneously treated groups, though the incidences were much lower than the belatedly treated groups.