The Effect of Brain-Derived Neurotrophic Factor on Periodontal Furcation Defects

This study aimed to observe the regenerative effect of brain-derived neurotrophic factor (BDNF) in a non-human primate furcation defect model. Class II furcation defects were created in the first and second molars of 8 non-human primates to simulate a clinical situation. The defect was filled with either, Group A: BDNF (500 µg/ml) in high-molecular weight-hyaluronic acid (HMW-HA), Group B: BDNF (50 µg/ml) in HMW-HA, Group C: HMW-HA acid only, Group D: empty defect, or Group E: BDNF (500 µg/ml) in saline. The healing status for all groups was observed at different time-points with micro computed tomography. The animals were euthanized after 11 weeks, and the tooth-bone specimens were subjected to histologic processing. The results showed that all groups seemed to successfully regenerate the alveolar buccal bone, however, only Group A regenerated the entire periodontal tissue, i.e., alveolar bone, cementum and periodontal ligament. It is suggested that the use of BDNF in combination with a scaffold such as the hyaluronic acid in periodontal furcation defects may be an effective treatment option.     

Application of autologous periosteal cells for the regeneration of class III furcation defects in Beagle dogs

The aim of this study was to evaluate the healing of class III furcation defects following transplantation of autogenous periosteal cells combined with β-tricalcium phosphate (β-TCP). Periosteal cells obtained from Beagle dogs’ periosteum explant cultures, were inoculated onto the surface of β-TCP. Class III furcation defects were created in the mandibular premolars. Three experimental groups were used to test the defects’ healing: group A, β-TCP seeded with periosteal cells were transplanted into the defects; group B, β-TCP alone was used for defect filling; and group C, the defect was without filling materials. Twelve weeks post surgery, the tissue samples were collected for histology, immunohistology and X-ray examination. It was found that both the length of newly formed periodontal ligament and the area of newly formed alveolar bone in group A, were significantly increased compared with both group B and C. Furthermore, both the proportion of newly formed periodontal ligament and newly formed alveolar bone in group A were much higher than those of group B and C. The quantity of cementum and its percentage in the defects (group A) were also significantly higher than those of group C. These results indicate that autogenous periosteal cells combined with β-TCP application can improve periodontal tissue regeneration in class III furcation defects.     

A clinical and radiological evaluation of DFDBA with amniotic membrane versus bovine derived xenograft with amniotic membrane in human periodontal grade II furcation defects

The purpose of the present study was to clinically and radiographically evaluate and compare the efficacy of demineralized freeze dried bone allograft (DFDBA) and bovine derived xenogenic bone graft (BDX) [Bio-Oss] with amniotic membrane (AM) as guided tissue regeneration (GTR) in the treatment of human periodontal Grade II buccal furcation defects. Ten patients suffering from chronic periodontitis, displaying bilateral Grade II buccal furcation defect, were randomly treated using DFDBA with AM (Experimental site A) or using bovine derived xenograft (BDX) with AM (Experimental site B). The clinical and radiographic parameters were recorded at baseline, 6 and 9 months. Healing was uneventful in all patients except one site which was treated with BDX + AM. At 9 months after therapy, soft tissue measurements for the DFDBA + AM group showed pocket depth (PD) reduction of 4.7 mm ± 0.58, and relative attachment level gain of 4.8 mm + 0.32, while the BDX + AM group showed a PD reduction of 4.4 mm ± 0.27, and AL gain of 5.1 mm ± 0.09. Osseous measurements showed bone fill of 2.1 mm ± 0.36 for the DFDBA + AM group and 2.43 mm ± 0.38 for the BDX + AM group. Percentage gain in bone was 76.3% for the DFDBA + AM group and 79.6% for the BDX + AM group. Statistical analysis revealed there was no statistical difference between the two materials in all measurements. Within the limits of the present study, it can be concluded that: (1) at 9 months after surgery both therapies resulted in significant PD reductions and CAL gains and (2) significant improvement was seen in bone fill and percentage gain with both the material, however, there was no significant difference between both.     

Recalcitrant abdominal wall hernias: long-term superiority of autologous tissue repair

Secondary repair of recurrent ventral hernia is difficult, and success depends on re-establishing the functional integrity of the abdominal wall. Current techniques used for closure of these defects have documented recurrence rates as high as 54 percent. The authors' 8-year experience utilizing variations of the components separation technique for autologous tissue repair of recalcitrant hernias emphasizes that recurrent or recalcitrant hernias benefit from the creation of a dynamic abdominal wall. A total of 389 patients were retrospectively identified as having abdominal wall defects, and 284 of these patients met the selection criteria. Study patients were grouped according to the type of surgical repair used. The recurrence rate was 20.7 percent over all study groups and was directly related to the extent of repair required. Group 1 patients (wide tissue undermining) had a recurrence rate of only 15 percent, while in group 2 (complete components separation), the recurrence rate was 22 percent. Group 3 patients (interpositional fascia lata graft) had a 29 percent recurrence rate. Time to recurrence was also significantly different across treatment groups, with study group 3 experiencing earlier hernia recurrence. The most frequent postoperative complication was wound infection, which was directly related to the repair performed. The relative odds of recurrence versus the risk factors of age, sex, perioperative steroid use, wound infection, defect size, and the presence of enterocutaneous fistula were studied with a logistic regression analysis. These factors did not possess statistical significance for predicting hernia recurrence. The preoperative presence of mesh was independently significant for hernia recurrence, increasing the relative odds 2.2 times (p = 0.01). Similarly, when other risk factors were controlled for, increasing the complexity of the treatment group, from study group 1 (wide tissue undermining) to study group 3 (interpositional fascia lata graft), also increased the odds of hernia recurrence 1.5-fold per group (p = 0.04). Average inpatient cost was $24,488. The length of inpatient stay ranged from 2 to 172 days (average, 12.8 days). The length of inpatient stay and costs were directly related to the extent of repair required. Using the analysis of variance test for multiple factors, the presence of an enterocutaneous fistula (p = 0.0014) or a postoperative wound infection (p = 0.008) independently increased the length of inpatient stay and hospital costs. A total of 108 successfully repaired patients were contacted by telephone and agreed to participate in a self-reported satisfaction survey. The patients noticed improvements in the appearance of their abdomen, in their postoperative emotional state, and in their ability to lift objects, arise from a chair or a bed, and exercise. These results suggest that recalcitrant hernia defects should be solved, when possible, by reconstructing a dynamic abdominal wall.     

胰岛素对糖尿病兔牙槽骨缺损修复的影响

目的：探讨胰岛素对糖尿病兔牙槽骨缺损修复治疗的效果,为糖尿病所致的牙周炎提供临床治疗的依据,方法：40只大耳白兔随机分为4组：A组制备健康兔的牙槽骨缺损;B组为胰岛素组,制备健康兔牙槽骨缺损后,用胰岛素治疗;C组为糖尿病组,制备糖尿病兔牙槽骨缺损;D组为糖尿病胰岛素治疗组,制备糖尿病兔牙槽骨缺损后,用胰岛素治疗。每组10只,缺损制备后4、8周各处死5只,对各组成骨情况进行组织学观察及测定。结果：组织学观察A、B、D组修复区可见大量新骨形成,以B组为显著;C组仅见少许成骨,多为纤维组织。新生骨面积比和成骨细胞数在4、8周时均为D组大于c组,B组大于A组,组间差异有统计学意义（P〈0．05）。证明应用胰岛素促进糖尿病兔缺损牙槽骨形成新骨的效果明显。结论：胰岛素能够促进糖尿病兔牙槽骨缺损的戍骨,为,临床上治疗糖尿病并发牙周炎提供一种新的手段。     

Streaming potential of human lumbar anulus fibrosus is anisotropic and affected by disc degeneration.

The streaming potential responses of non-degenerate and degenerate human anulus fibrosus were measured in a one-dimensional permeation configuration under static and dynamic loading conditions. The goal of this study was to investigate the influence of the changes in tissue structure and composition on the electrokinetic behavior of intervertebral disc tissues. It was found that the static streaming potential of the anulus fibrosus depended on the degenerative grade of the discs (p = 0.0001) and on the specimen orientation in which the fluid flows (p = 0.0001). For a statically applied pressure of 0.07 MPa, the ratio of streaming potential to applied pressure ranged from 5.3 to 6.9 mV/MPa and was largest for Grade I tissue with axial orientation and lowest for Grade III tissue with circumferential orientation. The dynamic streaming potential responses of anulus fibrosus were sensitive to the degeneration of the disc: the total harmonic distortion factor increased by 108%, from 3.92 +/- 0.66% (mean +/- SD) for Grade I specimens to 8.15 +/- 3.05% for Grades II and III specimens. The alteration of streaming potential reflects the changes in tissue composition and structure with degeneration. To our knowledge, this is the first reported data for the streaming potential of human intervertebral disc tissues. Knowledge of the streaming potential response of the intervertebral disc provides an understanding of potentially important signal transduction mechanisms in the disc and of the etiology of intervertebral disc degeneration.     

Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer. Blood vessel normalization was induced by two doses of thalidomide in tumor-bearing hamsters on 2 consecutive days. All studies in thalidomide-treated animals were performed 48 h after the first dose of thalidomide, previously established as the window of normalization. Biodistribution studies were performed with BPA at a dose of 15.5 mg (10)B/kg in thalidomide-treated (Th+) and untreated (Th-) tumor-bearing hamsters. The effect of blood vessel normalization prior to BPA administration on the efficacy of BNCT was assessed in in vivo BNCT studies at the RA-3 Nuclear Reactor in tumor-bearing hamsters. Group I was treated with BPA-BNCT after treatment with thalidomide (Th+ BPA-BNCT). Group II was treated with BPA-BNCT alone (Th- BPA-BNCT). Group III was treated with the beam only after treatment with thalidomide (Th+ BO), and Group IV was treated with the beam only (Th- BO). Groups I and II were given the same dose of BPA (15.5 mg (10)B/kg), and all groups (I-IV) were exposed to the same neutron fluence. Two additional groups were treated with the beam only at a higher dose to exacerbate mucositis in precancerous tissue and to explore the potential direct protective effect of thalidomide on radiation-induced mucositis in a scenario of more severe toxicity, i.e. Group V (Th+ hdBO) and Group VI (Th- hdBO). The animals were followed for 28 days. Biodistribution studies revealed no statistically significant differences in gross boron content between Th+ and Th- animals. Overall tumor control (complete response + partial response) at 28 days post-treatment was significantly higher for Group I (Th+ BPA-BNCT) than for Group II (Th- BPA-BNCT): 84 ± 3% compared to 67 ± 5%. Pretreatment with thalidomide did not induce statistically significant changes in overall tumor control induced by the beam only, i.e. 15 ± 5% in Group III (Th+ BO) and 18 ± 5% in Group IV (Th- BO), or in overall tumor control induced by the high-dose beam only, i.e. 60 ± 7% in Group V (Th+ hdBO) and 47 ± 10% in Group VI (Th- hdBO). BPA-BNCT alone (Group II) induced mucositis in precancerous tissue that reached Grades 3-4 in 80% of the animals, whereas pretreatment with thalidomide (Group I) prevented mucositis Grades 3 and 4 completely. Beam-only Group III (Th+ BO) exhibited only Grade 1 mucositis in precancerous tissue, whereas 17% of the animals in beam-only Group IV (Th- BO) reached Grade 2 mucositis. High-dose beam-only group V (Th+ hdBO) exhibited only Grade 2 mucositis, whereas high-dose beam-only group VI (Th- hdBO) reached Grade 3 mucositis in 83% of the animals. In all cases mucositis in precancerous tissue was reversible. No normal tissue radiotoxicity was observed with any of the protocols. Pretreatment with thalidomide enhanced the therapeutic efficacy of BNCT and reduced precancerous tissue toxicity.     

Repair of scalp defects using a tissue expander and Marlex mesh.

A simple technique using Marlex mesh and a tissue expander to cover scalp defects is described and two patients are presented. This technique is suitable for medium-sized defects that cannot be closed primarily. Marlex mesh is sutured to the wound edges in lieu of a temporary skin graft and to prevent enlargement of the defect during tissue expansion. The tissue expander is placed under adjacent normal scalp in a subgaleal pocket developed through the scalp defect. The scalp defect is closed secondarily using the expanded scalp flap. This technique was performed in two patients with satisfactory results. Marlex mesh obviates the need for a temporary skin graft to cover the scalp defect.     

Osteogenic ability of free perichondreal autografts in canine tibial defects: An experimental study

This study set out to establish the effect of transplanting perichondreum on bone healing at sites of tibial bone defects in an experimental dog model. Transplantation of free, autologous, non-vascularised, perichondreal grafts to the distal of right anteromedial plane side of the tibia was compared with non-transplantation on the proximal side of the same bone.

In experimental dogs (n = 7), a 5 cm piece segment of perichondreum, that has been excised from the thirteenth rib of the same animal, was transplanted to the middle defect fracture site of bone, but not to the control proximal defect fracture site.

The dogs were allowed to recover from the operation and were kept 21 days in cages, with free-range. On days 30 (Group I) and 45 (Group II) after operations, the dogs were euthanatized. Histopathologically, defects in 30 days treated perichondreum group were filled by new ossified tissue while control defects in the same period were not fully resurfaced. The new ossified tissue consisted of a thin and inadequate trabeculae. In 45 days treated groups, defects with transplanting perichondreum were filled by thick trabeculae converting into a compact bone tissue. The control defects of this group, however, were filled by an extreme callus overflowing to medulla and bone surface.

This study has provided evidence to show that autologous, non-vascularized perichondreum retains an osteogenic ability when transplanted to tibial bone defect sites. It appears that callus formation occurred within the perichondreum grafting which resembles that of enchondral and intramembranous ossification.     

骨碎补结合组织工程软骨促进软骨再生的实验研究

目的:评估骨碎补结合组织工程软骨治疗对实验兔软骨缺陷模型软骨再生的疗效。方法:将h IGF-1基因转染MSCs,并与脱细胞真皮基质(ADM)构建组织工程软骨。24只新西兰白兔随机分为A、B、C、D四组,A、C组进行自体软骨移植,B、D组进行改建的细胞-ADM移植。C、D组用40%骨碎补汤喂养4周,150 m L/d。第12周处死实验动物,分离缺损关节软骨部位,蜡块包埋染色,通过总体形态评价软骨再生组织。采用组织学评分评估再生软骨质量。采用甲苯胺蓝染色评价缺损部位产生软骨糖胺聚糖的情况。结果:与B组比较,C组和D组的新生软骨覆盖度、新骨髓的颜色、缺损边缘和表面粗糙度均显著提高(P0.05);再生软骨的组织学评分软骨表面评分显著改善(P0.05)。C组与D组具有比其他组更好的基质、细胞分布和表面指数。并且有较厚的透明样软骨组织,具有正常的糖胺聚糖产生。表明该治疗方法可以通过再生透明样软骨且没有不良事件来减少软骨缺陷。结论:工程软骨结合骨碎补治疗可显著改善兔膝关节软骨缺损修复的质量,为临床治疗软骨病变提供重要理论依据。     

Impaired processing and presentation by MHC class II proteins in human diabetic cells

The biochemical processing of and Ag presentation by MHC class II molecules were examined in B cell lines derived from pairs of identical twins discordant for type 1 diabetes. MHC class II defects detected exclusively in cells derived from the twins with autoimmunity included increased rates of transport to and subsequent turnover at the cell surface, inadequate glycosylation, and a reduced display at the cell surface of antigenic peptides. These defects appeared to be secondary to a decreased abundance of the p35 isoform of the invariant chain (Ii), a human-specific chaperone protein for MHC class II normally generated by use of an alternative translation start site. Stable transfection of diabetic B cell lines with an Ii p35 expression vector corrected the defects in MHC class II processing and peptide presentation. A defect in the expression of Ii p35 may thus result in impairment of Ag presentation by MHC class II molecules and thereby contribute to the development of type 1 diabetes in at-risk genotypes.     

Composite hyaluronate-type I collagen-fibrin scaffold in the therapy of osteochondral defects in miniature pigs

The potential of novel scaffold containing sodium hyaluronate, type I collagen, and fibrin was investigated in the regeneration of osteochondral defects in miniature pigs. Both autologous chondrocyte-seeded scaffolds and non-seeded scaffolds were implanted into two defects located in the non-weight-bearing zone of the femoral trochlea (defect A was located more distally and medially, defect B was located more proximally and laterally). Control defects were left untreated. Twelve weeks after the operation, the knees were evaluated in vivo using MRI. Six months after the implantation, the defects were analyzed using MRI, histological, and immunohistochemical analysis. In the A defects of chondrocyte-seeded scaffold group, hyaline cartilage and fibrocartilage was formed, containing type II collagen, acidic and neutral glycosaminoglycans while the non-seeded scaffold group was predominantly filled with fibrocartilage. Defects in the control group were predominantly filled with fibrous tissue. Histomorphometric analysis of photomicrographs revealed a significantly higher amount of hyaline cartilage in the cell-seeded scaffold group in A defects than in other groups. Both scaffold groups in A defects showed significantly less fibrous tissue than cell-seeded defects B and the control group. Both histological and MRI analysis proved that the novel composite scaffold has a potential to regenerate osteochondral defects within six months.     

Karl Fischer titration and coulometry for measurement of water content in small cartilage specimens.

This study evaluated the efficiency of Karl Fischer titration and coulometry for measurement of water content in small intact and defective cartilage specimens. Cartilage from the main weight-bearing zone of the medial condyle of 38 fresh sheep knees was used. Of these, 20 condyles had an intact cartilage, while defects (14 grade I and 4 grade II) were found in the rest. The mechanical hardness was determined as Shore A. Cartilage specimens of approximately 5 mg were analyzed in special devices for moisture measurement and then continuously heated up to 105 degrees C. The actual measurement was performed in an electric cell (coulometry). An electrode was laminated with hygroscopic phosphorus pentoxide. In the electrochemical reaction, H and O are liberated from the electrode. The requirement for electric energy correlates with the amount of water in the specimen. The water content in intact cartilage was 66.9%. Grade I (72.6%) and grade II (77.8%) defects had significantly higher water content. Significantly higher and faster spontaneous evaporation was observed in cartilage defects at room temperature. The water content and spontaneous water evaporation correlated with significantly lower mechanical hardness. The experimental design (combined method of thermogravimetry, Karl Fischer titration, and coulometry) was sufficient for evaluating the water content in small cartilage specimens. It is also possible to measure the temperature-dependent water liberation from cartilage specimens.     

Cathepsins B and L and their inhibitors stefin B and cystatin C as markers for malignant progression of benign meningiomas

Meningiomas are, in general, slowly growing benign tumors attached to the dura mater and composed of neoplastic meningothelial (arachnoidal) cells. They have a wide range of histopathological appearances and are classified, according to the aggressiveness of their growth and the risk of recurrence, as WHO grade I (benign) meningiomas, WHO grade II (atypical) meningiomas and WHO grade III anaplastic (malignant) meningiomas. As invasion of normal tissue may occur in all grades, independent biological markers are needed to identify the more aggressive and recurrent meningiomas. The lysosomal cysteine proteinases, cathepsins B and L, have been associated with tumor invasiveness and the aim of this study was therefore to evaluate them, together with their endogenous inhibitors stefin B and cystatin C, as potential markers for the aggressiveness of meningiomas. The expression of cathepsins B and L and their inhibitors stefin B and cystatin C in 21 benign (grade I) and 9 atypical (grade II) meningiomas has been compared by immunohistochemical staining, QRT-PCR and Northern blot analysis. The protein levels of cathepsins B (p=0.050) and L (p=0.019) were found to be significantly higher in atypical than in benign meningiomas. In contrast, their mRNA levels did not differ, indicating that the synthesis of cathepsins was accelerated at the translational level. Protein and mRNA levels of stefin B (p= 0.007), but not cystatin C, were significantly lower in atypical compared with benign meningiomas. The expression of cathepsins and inhibitors was not different between central and peripheral meningioma tissue or between histological subtypes of meningiomas, with the exception of cathepsin L, the level of which was significantly lower in transitional meningiomas. We conclude that higher protein levels of cathepsins B and L and lower mRNA levels of stefin B are potential diagnostic markers for invasive and aggressive behavior of meningiomas. The diagnostic and prognostic value for relapse of meningioma needs to be confirmed in a larger population of patients.     

Effect of the duration of infusion of urogastrone on intestinal regeneration in rabbits

Urogastrone (UG) increases the rate of mucosal regeneration on patched intestinal defects. Our aim was to determine the effect of the duration of UG administration on regeneration of serosa patched ileal defects in rabbits. Group I (n = 18) were controls. Group II (n = 15), Group III (n = 10) and Group IV (n = 5) received UG 1.5 micrograms/kg/h subcutaneously for 7 days, 14 days or 21 days respectively. Animals were sacrificed at 7 day intervals up to 21 days after patching. Neomucosal growth was significantly greater in the animals receiving UG and was greatest in Group IV. Group II and III animals had less contraction of the patched defect and greater neomucosal surface area than Group I animals at each interval but had a lesser effect than animals receiving UG continuously. Crypt cell production rate was significantly greater in UG treated animals at 7 and 14 days but fell to control levels at 21 days. Prolonging the duration of UG infusion increased the quantity of neomucosa produced by intestinal regeneration. However, UG stimulation of mucosal cell migration and proliferation occurred transiently within 14 days after patching.     

Improvement on in vitro maturation, fertilization and development of minke whale (Balaenoptera acutorostrata) oocytes

The aims of the present study were to improve in vitro maturation, fertilization and subsequent development of minke whale oocytes. We investigated the effects of different concentrations (0, 10 and 20%) of fetal whale serum (FWS) in maturation medium on nuclear maturation, morphological grade (A or B) of cumulus-oocyte complexes (COC) obtained from prepubertal and adult minke whales. Grade A (> or = 5 layers of cumulus cells) COC collected from the adult whales and cultured in the medium with 20% FWS had a higher (P < 0.05) maturation rate (31.8%) than those in the medium without FWS (0%). Adding FWS to the maturation medium significantly (P < 0.01) improved the proportion of oocytes at Metaphase II (M-II): without FWS (7.9%), with 10% (19.4%) and 20% (21.4%) FWS. However, sexual maturity of whales and COC grades were not significantly affected by M-II oocytes. When in vitro fertilization of matured oocytes was performed in the presence of 20% FWS or 0.6% BSA in the fertilization medium, the proportions of sperm penetration and two-pronuclei formation in matured oocytes were not significantly different. Grade A COC cultured in a culture medium supplemented with 10% FWS cleaved at a higher rate (15.4%, P < 0.05) than did Grade A and B COCs cultured in the medium without FWS (0%). Neither Grade A nor B COCs cleaved when the medium was without FWS. The proportions of cleaved oocytes increased (P < 0.05) with FWS supplementation (6.9% and 8.1% for 1.0% FWS and 20% FWS, respectively). Grade A COC was significantly (P < 0.05) superior in its ability to cleave (14.5%) and develop to morula (4.2%) compared with that of the oocytes from Grade B COC (2.5% and 0%). Coculture with granulosa cells during in vitro culture did not significantly affect cleavage and development to the morula stage. These results indicate that FWS addition in the maturation medium improved the rate of in vitro maturation and cleavage after insemination of minke whale oocytes. The BSA supplementation in fertilization medium was as effective as FWS supplementation for in vitro fertilization of matured oocytes. In vitro embryo production beyond the morula stage of minke whale oocytes could be possible, if Grade A COC was selected and cultured in the maturation medium supplemented with 10% or 20% FWS.     

Clinical Evaluation of Irradiated, Freeze-Dried Dura Mater Allograft as a Collagen-Based Barrier in Periodontal Osseous Defects

The objective of this study was to clinically evaluate freeze-dried dura mater allograft (FDDMA) provided by the Tata Memorial Hospital Tissue Bank, in various periodontal osseous defects and to observe any unwanted healing pattern or adverse reaction.Eleven systemically healthy patients with one infrabony/furcation defect and at least 6 mm or more loss of attachment at selected sites, were scheduled for surgery. At base-line, patients had a good maintenance regime, minimal gingival inflammation and mobility not more than 1 mm in the buccolingual plane (grade 2). The measurements taken were probing pocket depth, clinical attachment level, intrasurgical level of bone and radiographic level of bone. Instead of surgical re-entry, transgingival probing was performed after 12 months of surgery. After debridement the defects were filled with demineralised freeze-dried bone allograft and covered with FDDMA barrier. The results after 12 months were satisfactory (mean gain of attachment 4.33 mm and mean defect fill 3.91 mm). No adverse reaction, infection or delayed wound healing was noted throughout the study.     

Effect of urogastrone on intestinal regeneration is dose-dependent

Urogastrone (UG) increases the rate of intestinal regeneration in intestinal defects patched with adjacent serosal surfaces by increasing the rate of epithelial cell migration and proliferation. It also inhibits contraction of the patched intestinal defect. The purpose of this study was to determine the effect of the dose of UG on these processes. Twenty male New Zealand white rabbits (1.9-2.9 kg) had 2 x 5 cm ileal defects patched with adjacent caecal serosal surface. Group I (n = 6) served as the control group. Group II (n = 5), Group III (n = 5) and Group IV (n = 4) received UG 0.15, 1.5 and 4.5 micrograms/kg/h i.v. via mini-osmotic pumps. Seven days after patching, both epithelialization of the patched defect and neomucosal surface area were significantly increased by UG and the increases were dose-dependent. Contraction was not inhibited by the lowest dose of UG but was diminished by 1.5 micrograms/kg/h. Proliferative activity in both neomucosa and adjacent normal mucosa were increased in UG-treated animals with the greatest increase in rabbits receiving 1.5 and 4.5 micrograms/kg/h UG. The effect of UG on both epithelialization and contraction of patched intestinal defects is dose-dependent. Since the lowest dose of urogastrone increased epithelialization without increasing proliferative activity, stimulated cell migration appears to be the earliest effect of UG.     

Left ventricular markers of global dyssynchrony predict limited exercise capacity in heart failure, but not in patients with preserved ejection fraction

ABSTRACT: BACKGROUND: The aim of this study was to prospectively examine echocardiographic parameters that correlate and predict functional capacity assessed by 6 min walk test (6-MWT) in patients with heart failure (HF), irrespective of ejection fraction (EF). METHODS: In 147 HF patients (mean age 61 +/- 11 years, 50.3% male), a 6-MWT and an echo-Doppler study were performed in the same day. Global LV dyssynchrony was indirectly assessed by total isovolumic time - t-IVT [in s/min; calculated as: 60 -- (total ejection time + total filling time)], and Tei index (t-IVT/ejection time). Patients were divided into two groups based on the 6-MWT distance (Group I: <=300 m and Group II: >300 m), and also in two groups according to EF (Group A: LVEF >= 45% and Group B: LVEF < 45%). RESULTS: In the cohort of patients as a whole, the 6-MWT correlated with t-IVT (r = -0.49, p < 0.001) and Tei index (r = -0.43, p < 0.001) but not with any of the other clinical or echocardiographic parameters. Group I had lower hemoglobin level (p = 0.02), lower EF (p = 0.003), larger left atrium (p = 0.02), thicker interventricular septum (p = 0.02), lower A wave (p = 0.01) and lateral wall late diastolic myocardial velocity a' (p = 0.047), longer isovolumic relaxation time (r = 0.003) and longer t-IVT (p = 0.03), compared with Group II. In the patients cohort as a whole, only t-IVT ratio [1.257 (1.071-1.476), p = 0.005], LV EF [0.947 (0.903-0.993), p = 0.02], and E/A ratio [0.553 (0.315-0.972), p = 0.04] independently predicted poor 6-MWT performance (<300 m) in multivariate analysis. None of the echocardiographic measurements predicted exercise tolerance in HFpEF. CONCLUSION: In patients with HF, the limited exercise capacity, assessed by 6-MWT, is related mostly to severity of global LV dyssynchrony, more than EF or raised filling pressures. The lack of exercise predictors in HFpEF reflects its multifactorial pathophysiology.