Cellular compatibility of a gamma-irradiated modified siloxane-poly(lactic acid)-calcium carbonate hybrid membrane for guided bone regeneration

A bi-layered silicon-releasable membrane consisting of a siloxane-poly(lactic acid) (PLA)-vaterite hybrid material (Si-PVH) microfiber mesh and a PLA microfiber mesh has been developed by an electrospinning method for guided bone regeneration (GBR) application. The bi-layered membrane was modified to a three-laminar structure by sandwiching an additional PLA microfiber mesh between the Si-PVH and PLA microfiber meshes (Si-PVH/PLA membrane). In this study, the influence of gamma irradiation, used for sterilization, on biological properties of the Si-PVH/PLA membrane was evaluated with osteoblasts and fibroblasts. After gamma irradiation, while the average molecular weight of the Si-PVH/PLA membrane decreased, the Si-PVH/PLA membrane promoted cell proliferation and differentiation (alkaline phosphatase activity and calcification) of osteoblasts, compared with the poly(lactide-co-glycolide) membrane. These results suggest that the gamma-irradiated Si-PVH/PLA membrane is biocompatible with both fibroblasts and osteoblasts, and may have an application for GBR.     

A novel monoclonal antibody identified hepatic stem-like cells in rats

Both liver epithelial and oval cells are believed to be liver stem cells. We investigated the identification by producing monoclonal antibodies against liver epithelial cells. Monoclonal antibodies against hepatic stem-like cells (HSL cells) have been selected to follow the hepatic stem cells during hepatic regeneration and developmental changes in the liver. Monoclonal antibodies were induced by immunization of BALB/c mice with HSL cells established from the epithelial cells of the adult rat liver. The hybridomas were screened by indirect immunofluorescence staining of HSL cells. We produced a unique monoclonal antibody against HSL cells, MabH, which specifically recognizes liver epithelial cells. MabH did not react with liver parenchymal cells but did react with bile ductule cells under normal conditions in the adult liver. This antibody also reacted with oval cell lines and with the oval cells that appeared during liver regeneration. In addition, fetal liver cells showed immunoreactivity with MabH. Although the level of staining decreased after birth, some cells in the portal area remained highly reactive. These results suggested that liver epithelial cells, oval cells, and fetal liver cells possess a common cell marker of liver stem cells.     

HRAS mutants identified in Costello syndrome patients can induce cellular senescence: possible implications for the pathogenesis of Costello syndrome

Costello syndrome (CS) is a congenital disease that is characterized by a distinctive facial appearance, failure to thrive, mental retardation and cardiomyopathy. In 2005, we discovered that heterozygous germline mutations in HRAS caused CS. Several studies have shown that CS-associated HRAS mutations are clustered in codons 12 and 13, and mutations in other codons have also been identified. However, a comprehensive comparison of the substitutions identified in patients with CS has not been conducted. In the current study, we identified four mutations (p.G12S, p.G12A, p.G12C and p.G12D) in 21 patients and analyzed the associated clinical manifestations of CS in these individuals. To examine functional differences among the identified mutations, we characterized a total of nine HRAS mutants, including seven distinct substitutions in codons 12 and 13, p.K117R and p.A146T. The p.A146T mutant demonstrated the weakest Raf-binding activity, and the p.K117R and p.A146T mutants had weaker effects on downstream c-Jun N-terminal kinase signaling than did codon 12 or 13 mutants. We demonstrated that these mutant HRAS proteins induced senescence when overexpressed in human fibroblasts. Oncogene-induced senescence is a cellular reaction that controls cell proliferation in response to oncogenic mutation and it has been considered one of the tumor suppression mechanisms in vivo. Our findings suggest that the HRAS mutations identified in CS are sufficient to cause oncogene-induced senescence and that cellular senescence might therefore contribute to the pathogenesis of CS.     

In vitro antitrypanosomal activity of some phenolic compounds from propolis and lactones from Fijian Kawa (Piper methysticum)

During our search to discover new antitrypanosomal compounds, eight known plant compounds (three phenolic compounds and five kawa lactones) were evaluated for in vitro activity against Trypanosoma brucei brucei. Among them, we found two phenolic compounds and three kawa lactones possessing an α-pyrone influenced antitrypanosomal property. In particular, β-phenethyl caffeate, farnesyl caffeate and dihydrokawain exhibited high or moderate selective and potent antitrypanosomal activity in vitro. We detail here the antitrypanosomal activity and cytotoxicities of the compounds, in comparison with two commonly used antitrypanosomal drugs (eflornithine and suramin). Our findings represent the first report of the promising trypanocidal activity of these compounds.     

New spirostanol glycosides from Solanum nigrum and S. jasminoides

A new characteristic steroidal glycoside possessing a hydroxyl group at C-23, inunigroside A (1), was isolated from the withered berries of Solanum nigrum L. On the basis of spectroscopic analysis, the structure of 1 was characterized as (5α,22S,23S,25R)-3β,23-dihydroxyspirostane 3-O-β-lycotetraoside. Next, a major steroidal sapogenol, (22R, 25S)-3β,15α-dihydroxy-spirost-5-ene (3), was obtained from the acid hydrolysate of the methanolic extract of the aerial parts of Solanum jasminoides L. A new bisdesmoside, 3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl (22R,25S)-3β,15α-dihydroxyspirost-5-ene 15-O-α-L-rhamnopyranoside (4), named jasminoside A, was isolated from the methanolic extract of S. jasminoides.     

In vitro antitrypanosomal activity of bis(bibenzyls)s and bibenzyls from liverworts against <Emphasis Type="Italic">Trypanosoma brucei</Emphasis>

During the course of our screening program to discover new antitrypanosomal compounds, 17 known plant aromatic compounds [12 bis(bibenzyls)s and 5 bibenzyls] were evaluated for in vitro activity against Trypanosoma brucei brucei. Sixteen compounds were found to exhibit antitrypanosomal activity. In particular, three compounds, marchantin A (1), plagiochin A (5) and 2(R)-2-isopropenyl-6,7-dihydroxy-4-(2-phenylethyl)dihydrobenzofuran (16) demonstrated moderate selective and potent antitrypanosomal activities in vitro. We detail here the antitrypanosomal properties and cytotoxicities of the compounds in comparison with two commonly used therapeutic drugs, eflornithine and suramin. Our finding represents the first report of the promising trypanocidal activity of these compounds. The research also provides valuable insight into structure–activity relationships and the possible mode of action of the compounds.     

Functional and occupational characteristics associated with very early return to work after stroke in Japan

Tanaka H, Toyonaga T, Hashimoto H. Functional and occupational characteristics associated with very early return to work after stroke in Japan.

Objectives

To examine clinical, functional, and occupational factors associated with very early return to work after stroke, and to identify factors manageable through occupational arrangements, patient education, and other welfare programs.

Design

Prospective cohort study.

Setting

Acute care of the first stroke event in 21 acute care hospitals specializing in clinical and occupational health.

Participants

Consecutive patients with stroke in working age (N=335).

Interventions

Not applicable.

Main Outcome Measures

Data pertaining to demographic, clinical, functional, and occupational factors were collected from hospital records. Multiple logistic regression analysis with backward stepwise selection was used to obtain a final model to predict the likelihood of patients returning very early to work.

Results

The sample was predominantly men (80%) with a mean age ± SD of 55.2±7.2 years; 30% succeeded in very early return to work. After adjusting for age, sex, and modified Rankin scale at discharge, white-collar versus blue-collar occupation (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.00–4.21), Barthel Index at onset (OR, 1.02; 95% CI, 1.01–1.03), and employment status at discharge (OR, 17.36; 95% CI, 3.15–95.72) were selected in the final model as significant predictors of very early return to work. Patients with mild physical disability and higher cortical dysfunction found it more difficult to return to work very early compared with those without these conditions.

Conclusions

We found that patients with stroke who had mild disability at onset, were in a white collar occupation, and were employed at discharge were more likely to return to work very early, even after adjusting for functional levels at discharge. Cognitive rehabilitation is needed for those with mild physical disability and higher cortical dysfunction.     

Resting energy expenditure in patients undergoing pylorus preserving pancreatoduodenectomies for bile duct cancer or pancreatic tumors

We measured the energy expenditure weekly in patients undergoing a pylorus preserving pancreatoduodenectomy for bile duct cancer or pancreatic tumors. Twelve patients (5 women and 7 men; mean age 70.1 years) were enrolled in this study, and their resting energy expenditure levels were determined by indirect calorimetry. In these patients, a significant correlation was observed between the measured resting energy expenditures and the predicted resting energy expenditures calculated by the Harris-Benedict equation. The resting energy expenditures measured before surgery were almost the same as the predicted resting energy expenditures (measured resting energy expenditure: 22.4 ± 3.9 kcal/kg/day vs predicted resting energy expenditure: 21.7 ± 2.0 kcal/kg/day). The measured resting energy expenditure/predicted resting energy expenditure ratio, which reflects the stress factor, was 1.02 ± 0.10. After the pylorus preserving pancreatoduodenectomy, a significant increase in energy expenditure was observed, and the measured resting energy expenditure was 25.7 ± 3.5 kcal/kg/day on postoperative day 7 and 25.4 ± 4.9 kcal/kg/day on postoperative day 14. The measured resting energy expenditure/predicted resting energy expenditure ratio was 1.16 ± 0.14 on postoperative day 7, and 1.16 ± 0.18 on postoperative day 14 respectively. In conclusion, patients undergoing a pylorus preserving pancreatoduodenectomy showed a hyper-metabolic status as evaluated by their measured resting energy expenditure/predicted resting energy expenditure ratio. From our observations, we recommend that nutritional management based on 30 kcal/body weight/day (calculated by the measured resting energy expenditure×activity factor 1.2–1.3) may be optimal for patients undergoing a pylorus preserving pancreatoduodenectomy.     

Successful treatment with nilotinib after imatinib failure in a CML patient with a four-way Ph chromosome translocation and point mutations in BCR/ABL gene

Chronic myelogenous leukemia (CML) is characterized by Philadelphia (Ph) chromosome with a chimeric gene BCR–ABL created by reciprocal t(9:22) (q34;q11) translocation. Variant Ph chromosome translocations involving chromosomes other than 9 and 22 are found in 5–10% of CML cases. We here report a CML patient who carries a four-way Ph chromosome translocation, t(9;22;15;19) (q34;q11;q15;q13). The patient was diagnosed in 1997 and initially treated with hydroxyurea. In 2002, treatment with imatinib, a selective BCR–ABL tyrosine kinase inhibitor (TKI), was started but Ph-positive chromosomes remained at the levels of 42–65%, indicating imatinib failure. In 2006, the point mutations of F359I and L387M were detected in BCR/ABL gene, which may be related to imatinib failure. Treatment with nilotinib, a TKI with high target specificity, was then started which resulted in durable major molecular response. Administration of nilotinib offered an effective treatment in a CML patient with variant Ph chromosome translocations and BCR–ABL point mutations after imatinib failure.