Wound healing effect of methanolic leaf extract of Napoleona vogelii(Family:Lecythidaceae) in rats

Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.     

Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes

Using monoclonal antibodies (mAbs) specific for different natural killer (NK) receptors, we studied the lymphocyte population from 18 patients with NK-type lymphoproliferative disease of granular lymphocytes (LDGL). The analysis of both resting and cultured NK cell populations demonstrated that these patients are frequently characterized by NK cells displaying a homogeneous staining with given anti-killer Ig-like receptor (anti-KIR) mAb (11 of 18 patients). In most patients NK cells were characterized by the CD94/NKG2A+ phenotype, whereas only a minor fraction of the cases expressed CD94/NKG2C. In 7 of these patients we could also assess the function of the various NK receptors. Remarkably those KIR molecules that, in each patient, homogeneously marked the NK cell expansion were found to display an activating function as determined by cross-linking with specific anti-KIR mAb. The KIR genotype analysis performed in 13 of 18 cases revealed that in NK-type LDGL certain activating KIRs, as well as certain infrequent KIR genotypes, were detected with higher frequencies as compared to previously analyzed healthy donors. Moreover, most KIR genotypes included multiple genes coding for activating KIRs. The analysis of non-HLA-specific triggering receptors indicated that the natural cytotoxicity receptors (NKp46, NKp30) were expressed at significantly low levels in freshly drawn NK cells from most patients analyzed. However, in most instances the expression of NKp46 and NKp30 could be up-regulated on culture in interleukin 2. Our data indicate that in NK-LDGL the expanded subset is frequently characterized by the expression of a given activating KIR, suggesting a direct role for these molecules in the pathogenetic mechanisms of this disorder.     

Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady- state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.     

Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one iron chelators in overloaded and nonoverloaded mice

Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied using chemical iron quantitation (P less than .001) and with Perls' stain (P less than .01). Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to 63% with CP51, compared with 46% removal for desferrioxamine (DFO). There was no significant reduction in splenic or cardiac iron with any chelator. There were no deaths in iron-overloaded animals receiving any of the hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded groups as a whole (P less than .03). No weight loss was observed with any chelator. Significant reductions in hemoglobin and white cell count were observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies were observed in the centrilobular hepatocytes of animals administered each of the hydroxypyridin-4-ones, while the DFO-treated and control groups showed no such changes.     

Neoadjuvant chemoradiation with concomitant boost radiotherapy associated to capecitabine in rectal cancer patients

Purpose

The primary end-points were complete pathological response and local control. Secondary end-points were survivals, anal sphincter preservation, and toxicity profile.

Methods

Patients with T3/T4 and or N+ rectal cancer (n?=?65) were treated with preoperative concomitant boost radiotherapy (55 Gy/25 fractions) associated to concurrent chemotherapy with oral capecitabine.

Results

All patients completed the programmed treatment. The complete pathological response was achieved by 17 % of the patients. Anal sphincter preservation surgery was possible for 86 % of the patients with low rectal cancer (≤5 cm from the anal verge). The T-stage and N-stage downstaging were achieved by 40 and 58 % of the patients, respectively. Circumferential radial margin was involved (close/positive) in eight patients. After a median follow-up of 26 months, local and distant recurrence occurred in two and 11 patients, respectively. The 3-year overall survival and disease-free survival were 86.8 and 81 %, respectively. Non-hematological?≥?grade 3 toxicities were observed in 15 % of the patients. On univariate analysis N-downstaging and positive circumferential radial margin were significantly associated with worse overall survival (p?=?0.003 and p?=?0.023, respectively), disease-free survival (p?=?0.001 and p?=?0.036, respectively), and metastasis-free survival (MFS) (p?=?0.001 and p?=?0.038, respectively).On multivariate analysis, the N-downstaging were significantly associated with better overall survival (OS) (p?=?0.022).

Conclusions

Our data support the efficacy of preoperative treatment for rectal cancer in terms of local outcomes. Radiation treatment intensification may have a biological rationale; longer follow-up is needed.     

Novel Pancreas Organogenesis Markers Refine the Pancreatic Differentiation Roadmap of Embryonic Stem cells

The generation of pancreatic endocrine and exocrine functional precursors from embryonic stem cells (ESCs) is an intriguing opportunity to address cell therapy challenges. The main goal of cellular regeneration is to derive, in vitro, pancreatic progenitor cells (PPCs) that retain the capacity to differentiate following the in vivo developmental ontogeny. In our work, we aim to refine the pancreatic in vitro cellular transitions, through the identification of the intrinsic factors that mark the pancreas budding process at embryonic stage 10.5 (E10.5), in which pancreas precursor specification predominantly occurs. We identified a cohort of genes (Bex1, Nepn, Pcbd1, Prdxdd1, Rnf160, Slc2a1, and Tff3) that marked the pancreas budding genesis, and above all signaled ESC differentiation transitions during pancreatic lineage commitment. Noticeably, we demonstrated that the expression of Nepn marked a naïve pancreatic cellular state that resembled PPC-like specification. Our data considerably improve the comprehension of pancreatic cellular ontogeny, which could be critical for implementing pluripotent stem cells programming and reprogramming toward pancreatic lineage commitment.