Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

The Quality of Life of Family Caregivers of Eating Disorder Patients

Having a relative with an eating disorder (ED) affects the life of family caregivers and may thus affect their quality of life. To study this aspect, 40 caregivers of ED patients filled out a health-related quality of life questionnaire (Short Form-36) and a questionnaire on the impact of the ED on various areas of life domains, and on the relationship with the ED patient and the need for professional support. Quality of life of caregivers was worse than in a normal reference group. Specifically, mental health, vitality and emotional role functioning were reported to be most impaired. ED appeared to affect families’ lives substantially. In response to the ED, caregivers felt anxious, powerless, sad, or desperate. The relationship of the caregiver with the ED patient had also changed. Caregivers were more worried, lost their trust, and reported more conflicts. Seventy five percent welcomed professional support. Caregivers need practical advice, information on ED, and emotional support. Quality of life of caregivers should be addressed in the treatment of ED.     

Surrogate markers for cerebral blood flow correlate with [18F]‐fallypride binding potential at dopamine D2/3 receptors in human striatum

Positron emission tomography (PET) with the high affinity dopamine D_2/3 receptor ligand [¹⁸F]‐fallypride affords estimates of the binding potential (BP_ND) in extra‐striatal regions of low receptor abundance, but the sufficient recording time for accurate measurements in striatum has been called into question. We have earlier argued that transient equilibrium measurements are obtained in striatum with [¹⁸F]‐fallypride PET recordings of 3 h duration, which may be the practical limit for clinical investigations without interrupted scanning. However, the high extraction fraction of [¹⁸F]‐fallypride predicts flow‐dependence of tracer delivery to brain, which may be a source of variance of the apparent BP_ND in regions of high binding. To test this prediction, we conducted a retrospective analysis of [¹⁸F]‐fallypride PET data from a group of 50 healthy volunteers (age 18–58 years [mean ± SD: 32.6 ± 10.6), who had participated in clinical studies without arterial input measurements. We used the initial 120‐s integral (AUC) of the venous confluence (VC) as a surrogate marker for cerebral blood flow (CBF) and tested for correlations between regional estimates of BP_ND calculated by the simplified reference tissue model (SRTM) and the individual VC‐AUC. The magnitude of BP_ND in a high binding region (putamen), but not in a low binding region (thalamus) correlated positively with VC‐AUC, suggesting that approximately 9% of the variance in the [¹⁸F]‐fallypride BP_ND in putamen can be attributed to individual differences in this surrogate marker for CBF, a contribution equal in magnitude to the effects of age on BP_ND in putamen of the present healthy control group. Synapse, 2013. © 2012 Wiley Periodicals, Inc.     

亚麻子水提液对DPP-4及α-葡萄糖苷酶活性抑制实验研究

目的通过观察亚麻子水提液对二肽基肽酶-4（DPP-4）、α-葡萄糖苷酶抑制作用,为该药防治糖尿病提供实验依据。方法①以DPP-4酶、缓冲液、底物建立DPP-4抑制剂的体外筛选体系,对亚麻子水提液进行抑制实验,采用发色底物法测定吸光度（OD）,计算DPP-4抑制率及IC50值;②以蔗糖为底物建立α-葡萄糖苷酶活性抑制模型,采用葡萄糖氧化酶法测定亚麻子水提液对α-葡萄糖苷酶的抑制作用,计算其抑制率和IC50值。结果①亚麻子具有轻度DPP-4抑制作用,其IC50值738.20mg/L;②亚麻子具有α-葡萄糖苷酶抑制作用,其IC50值为365.9mg/mL。结论亚麻子水提液可一定程度地抑制DPP-4及α-葡萄糖苷酶活性。     

广州市荔湾区青少年脊柱侧凸患病率的调查研究

目的了解广州市荔湾区青少年脊柱侧凸的患病率。方法 2011年7月~2012年1月对荔湾区8351名7~15岁在校中小学生进行了脊柱侧凸普查,应用脊柱侧凸两检法（体检、X线照片）,体检阳性或可疑阳性者到医院照脊柱全长正侧位X片,采用Cobb法测量,Cobb角≥10°诊断为脊柱侧凸。结果一检阳性结果 175名（2.1%）,二检阳性为85名（1.02%）,男性31名,女性54名,男∶女患病率比为1∶1.76,其中特发性脊柱侧凸81名,占95.3%,先天性侧凸3名,神经肌肉源性1名。结论荔湾区中小学生脊柱侧凸发病率为1.02%,通过普查,可以早发现、早诊断青少年脊柱侧凸,及时选择适当方法进行治疗。     

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Hematopoietic defects in mice lacking the sialomucin CD34

Although the pluripotent hematopoietic stem cell can only be definitively identified by its ability to reconstitute the various mature blood lineages, a diversity of cell surface antigens have also been specifically recognized on this subset of hematopoietic progenitors. One such stem cell-associated antigen is the sialomucin CD34, a highly O-glycosylated cell surface glycoprotein that has also been shown to be expressed on all vascular endothelial cells throughout murine embryogenesis as well as in the adult. The functional significance of CD34 expression on hematopoietic progenitor cells and developing blood vessels is unknown. To analyze the involvement of CD34 in hematopoiesis, we have produced both embryonic stem (ES) cells and mice that are null for the expression of this mucin. Analysis of yolk saclike hematopoietic development in embryoid bodies derived from CD34- null ES cells showed a significant delay in both erythroid and myeloid differentiation that could be reversed by transfection of the mutant ES cells with CD34 constructs expressing either a complete or truncated cytoplasmic domain. Measurements of colony-forming activity of hematopoietic progenitor cells derived from yolk sacs or fetal livers isolated from CD34-null embryos also showed a decreased number of these precursor cells. In spite of these diminished embryonic hematopoietic progenitor numbers, the CD34-null mice developed normally, and the hematopoietic profile of adult blood appeared typical. However, the colony-forming activity of hematopoietic progenitors derived from both bone marrow and spleen is significantly reduced in adult CD34-deficient animals, and these CD34-deficient progenitors also appear to be unable to expand in liquid cultures in response to hematopoietic growth factors. Even with these apparent progenitor cell deficiencies, CD34- null animals showed kinetics of erythroid, myeloid, and platelet recovery after sublethal irradiation that are indistinguishable from wild-type mice. These data strongly suggest that CD34 plays an important role in the formation of progenitor cells during both embryonic and adult hematopoiesis. However, the hematopoietic sites of adult CD34-deficient mice may still have a significant reservoir of progenitor cells that allows for normal recovery after nonmyeloablative peripheral cell depletion.     

二氧化碳气腹对肿瘤细胞生长和播散影响的研究

目的　研究静脉使用 5 %NaHCO3 纠正CO2 气腹造成的酸中毒能否改善其对肿瘤细胞的促生长和播散作用。方法　观察静脉推注 5 %NaHCO3 的CO2 气腹组、CO2 气腹组及对照组带瘤Wister大鼠的肿瘤生长及穿刺点转移情况。结果　静脉推注 5 %NaHCO3 的CO2 气腹组、CO2 气腹组及对照组肿瘤的重量、体积和腹水体积有差异 ,但无统计学意义。穿刺点转移率无明显差异。结论　CO2 气腹影响肿瘤细胞生长和播散的机制复杂 ,不能完全以CO2 引起机体酸中毒解释。未找到通过静脉推注 5 %NaHCO3 可改善CO2 气腹对肿瘤细胞生长影响的基础理论依据。     

Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.     

Induction of proliferation of B prolymphocytic leukemia cells by phorbol ester and native or recombinant interferon-gamma

Phorbol ester phorbol myristate acetate (PMA) induces proliferation in nonmalignant human B cells and B cells from a patient with B prolymphocytic leukemia (B-PLL). Mitogen-free T cell-derived conditioned medium acts synergistically with PMA in inducing proliferation of B-PLL cells but does not enhance the PMA-stimulated outgrowth of nonmalignant B cells. Interleukin 2 (IL-2) has no effect on the outgrowth of B-PLL cells, and monoclonal antibodies against the IL-2 receptor do not influence the response to PMA and conditioned medium. Recombinant interferon-gamma (IFN-gamma), in contrast, is a potent enhancer of PMA-induced proliferation of B-PLL cells. With gel filtration techniques and with the use of anti-IFN-gamma antibodies, it is shown that IFN-gamma in the conditioned medium is responsible for the observed increase in B-PLL cell proliferation. Preincubation of B- PLL cells with IFN-gamma induces responsiveness to PMA, whereas IFN- gamma alone had no effect on these cells when pretreated with PMA. The combined data show that, in the presence of PMA, native and recombinant IFN-gamma are growth factors for B cells from a B-PLL patient and that IL-2 is not involved in this process.