Suramin inhibits bone resorption and reduces osteoblast number in a neonatal mouse calvarial bone resorption assay.

The antineoplastic properties of suramin, a polyanionic agent with demonstrated antigrowth factor activity, are under evaluation in vitro, in vivo, and in clinical trials. Suramin has been shown to have antitumor activity in patients with advanced, hormone refractory prostate cancer. During these trials, significant resolution of osseous pain was observed in nearly three quarters of the patients treated with suramin. To evaluate the effect of suramin on bone cells, we studied the effect of suramin on bone resorption in a neonatal mouse calvarial assay. Suramin inhibited bone-resorbing activity in a dose-related fashion and had an additive effect with calcitonin. Calvaria pretreated with suramin had less bone-resorbing activity, fewer attached osteoblasts, and less medium alkaline phosphatase activity than control calvaria. Suramin also inhibited osteoclastic release of tritiated proline from labeled bone in a dose-dependent fashion. The effect of metastatic prostate carcinoma on bone is incompletely understood, but may be moderated by tumor-produced factors and/or cytokines. The effects of several such agents, therefore, were examined in combination with suramin. Bone resorption induced by PTH, epidermal growth factor, tumor necrosis factor, and a tumor-produced factor, PTH related-protein, was blocked by suramin. The ability of suramin to inhibit the bone-resorbing effects of several cytokines suggests that its mechanism may involve direct action on bone metabolism. Autoradiography performed on calvaria treated with labeled suramin demonstrated heavy deposition of suramin on the outer surface of the matrix, adjacent to osteoblasts and osteoclasts lining the outer table, suggesting that bone cells may be subject to high local concentrations of the drug, in keeping with this hypothesis.     

Selection for Streptococcus mutans with an altered xylitol transport capacity in chronic xylitol consumers

The effect of long-term consumption of refined xylitol on the natural populations of S. mutans in the human oral cavity has been investigated. Fifty-four S. mutans strains were isolated from adults and children who had been consuming commercial food products containing xylitol for a period of from 1 1/2 to 10 years. Twenty isolates were also obtained from control subjects who had never consumed xylitol-containing commercial food products. The inhibitory effect of xylitol on the isolated strains was determined by monitoring growth on glucose in the presence or absence of xylitol. This was used to define the sensitivity of each isolate to xylitol. Phosphoenolpyruvate:sugar phosphotransferase (PEP-PTS) activities were measured by means of the soluble and membrane fractions prepared from strains from both study populations. It was found that 87% of the fresh isolates from xylitol consumers were xylitol-resistant (XR), compared with only 10% of the strains isolated from the control subjects. The XR strains had low constitutive fructose PTS activity and very low xylitol-phosphorylating capacity. The xylitol-sensitive (XS) strains, however, had much higher levels of constitutive fructose PTS activity and phosphorylated xylitol 16 times more rapidly than did the XR strains. Evidence for the phosphorylation of xylitol by a fructose PEP-PTS in the XS strains was obtained. The growth inhibition by the intracellular accumulation of non-metabolizable toxic xylitol phosphate and its prevention by the presence of fructose are discussed.     

Serous papillary carcinoma of the endometrium arising from endometrial polyps: a clinical, histological, and immunohistochemical study of 13 cases

Serous papillary carcinoma is an aggressive tumor. Point mutations in the p53 suppressor gene might explain in part the rapid growth of this malignant tumor and its unfavorable outcome. The aims of this study were to evaluate the behavior of serous papillary carcinoma developing in endometrial polyps and to assess the p53 protein overexpression. Patients included in this study were treated in our institution between 1982 and 2003. All clinical and pathological materials were examined. A p53 protein immunohistochemical analysis was performed on paraffin-embedded tissues. Thirteen serous papillary carcinomas arising from benign polyps of the endometrium were identified. The patients' age averaged 73 years. All patients were treated surgically. After an average follow-up of 22 months, 54% of the patients were dead or alive with disease. Of 10 serous papillary carcinomas, 8 (80%) for which paraffin blocks were available overexpressed the p53 protein. A serous papillary carcinoma arising from benign polyps of the endometrium remains a malignant neoplasia with an unfavorable outcome even if the primary tumor is limited to the polyp. The high rate of protein p53 overexpression suggests that a p53 gene mutation occurs early in the disease and might explain the rapid growth of the tumor.     

Effect of nutritional constraints on the biosynthesis of the components of the phosphoenolpyruvate: sugar phosphotransferase system in a fresh isolate of Streptococcus mutans.

A procedure for the purification of enzyme I (EI) and the protein HPr, the general components of the phosphoenolpyruvate:sugar phosphotransferase system, from Streptococcus mutans serotype c is presented. The method was also applied successfully to the purification of EI and HPr from Streptococcus salivarius, Streptococcus sobrinus, and Streptococcus sanguis. Using specific antibodies obtained against the proteins purified from S. mutans DR0001, we determined quantitatively by rocket electrophoresis the cellular levels of EI and HPr in a freshly isolated strain of S. mutans grown under various conditions in continuous culture. The activity of a few specific EIIs was also determined by an in vitro phosphorylation test. Results indicated that maximum EII activities for glucose, mannose, and 2-deoxyglucose were obtained under conditions of glucose limitation, at pH 7.0 and low dilution rate (D = 0.057/h). Increasing the amount of glucose or the dilution rate (D = 0.40/h) or decreasing the pH from 7.0 to 5.5 resulted in a 1.4- to 24-fold decrease in these activities. The EII activity for fructose was not influenced by the growth conditions in the same way as the other EIIs. The fructose EII was highest at pH 5.5 and at high dilution rate under conditions of glucose or nitrogen limitation and was always repressed at pH 7.0 and at low dilution rates. The intracellular levels of EI were also dependent on the growth conditions. The highest concentration (0.65 nmol/mg of protein) was observed in cells grown under glucose limitation at pH 7.0 and high dilution rate, and the lowest concentration (0.12 nmol/mg of protein) was found in cells grown under glucose excess at pH 7.0 and high dilution rate. The other general component of the phosphoenolpyruvate:sugar phosphotransferase system, the protein HPr, was not influenced significantly by varying growth conditions.     

Fischer 344 rats display age-related memory deficits in trace fear conditioning

A functional hippocampus is required for trace fear conditioning, which involves learning the association of a tone and shock that are separated over time. Young and aged rats received 10 trace conditioning trials. Twenty-four hours later, rats were tested for fear to the tone in a novel chamber by measuring freezing. The results showed significantly lower levels of freezing in aged rats as compared with young rats, which provides evidence of age-related memory impairments. Pseudorandom conditioning groups showed low levels of freezing, indicative of no associative memory. Age-related memory deficits were not found with delay conditioning, which suggests no age-related sensory-motor deficits. These data suggest that aging hinders the ability of the hippocampus to process information separated over time.     

Cardiovascular effects of hemoglobin response in patients receiving epoetin alfa and oral iron in heart failure with a preserved ejection fraction

Background Previous data from a recently conducted prospective, single blind randomized clinical trial among community dwelling older patients with heart failure with a preserved ejection fraction （HFPEF） and anemia randomized to treatment with epoetin alfa （erythro-poiesis-stimulating agents, ESA） vs. placebo did not demonstrate significant benefits of therapy regarding left ventricular （LV） structure, functional capacity, or quality of life （QOL）. However, several patients randomized to the treatment arm were non-responders with a subop-timal increase in hemoglobin. All patients in the trial also received oral ferrous gluconate, which could have contributed to increases in he-moglobin observed in those receiving placebo. Accordingly, we performed an analysis separating patients into responders vs. non-responders in order to determine if measured improvement in anemia would have any effect on clinical endpoints. Methods A total of 56 patients （age 77 ± 11 years, 68%female） were recruited who had anemia defined as a hemoglobin of≤12 g/dL （average, 10.4 ± 1 g/dL） with HFPEF defined as having NHANES-CHF （National Health And Nutrition Examination Survey：Congestive Heart Failure） criteria score of≥3 and an ejection fraction of＆gt;40%（average EF=63%±15%）. Patients were randomly allocated to receive either ESA and ferrous gluconate or ferrous gluconate only. In this analysis, a responder was defined as a patient with an increase of 1 g/dL in the first 4 weeks of the trial. Re-sults Nineteen subjects were classified as responders compared to 33 non-responders. While the average hemoglobin increased signifi-cantly at the end of 6 months for responders （1.8 ± 0.3 vs. 0.8 ± 0.2 g/dL, P = 0.004）, 50% of the subjects assigned to ESA were non-responders. Left ventricular function including ejection fraction （P=0.32） and end diastolic volume （P=0.59） was unchanged in res-ponders compared to non-responders. Responders also showed no significant improvements in New York Heart Association （NYHA） class, Six Minute Walk Test （6 MWT） and peak VO2. Though QOL improved significantly within each group, there was no difference between the two. Conclusions A significant hemoglobin response to anemia treatment with ESA and oral iron does not lead to differences in LV re-modeling, functional status, or QOL. Additionally, a significant percent of older adults with HFPEF and anemia do not respond to ESA ther-apy. Given the results of this small trial, it appears as though using objective improvements in anemia as a marker in older adult subjects with HFPEF does not have significant clinical utility.     

Gunshot wounds to the spine in post-Katrina New Orleans

Background

Gunshot wounds (GSW) to the spine represent a major health concern within today's society. Our study assessed the epidemiologic characteristics of patients with GSW to the spine treated in New Orleans.

Patients and methods

A retrospective chart review was performed from January 2007 through November 2011 on all the patients who were seen in the emergency room and diagnosed with a gunshot wound to the spine. Epidemiologic factors, as well as the results of admission toxicology screening, were noted. Outcome analysis was performed on patients undergoing conservative versus operative management for their injuries. Clinical outcomes were assessed using the ASIA classification system. Complications related to initial injury, neurosurgical procedures, and hospital stay were noted.

Results

A total of 147 patients were enrolled. Of those diagnosed with a GSW to the spine, 88 (59.8%) received an admission toxicology screen. Seventy-three (83%) patients out of those tested had a positive screen, with the most common substances detected being cannabis, cocaine, and alcohol. In regards to management, 127 (87%) patients were treated conservatively and only one (0.7%) patient improved clinically from ASIA D to E. Of the 20 patients who underwent surgery, one (5%) patient had clinical improvement post-operatively from ASIA C to D.

Conclusions

This study evaluates the largest number of patients with GSW to the spine per year treated in a single centre, illustrating the violent nature of New Orleans. In this urban population, there was a clear correlation between drug use and suffering a GSW to the spine. Surgical intervention was seldom indicated in these patients and was predominately used for fixation of unstable fractures and decompression of compressive injuries, particularly below T11. Minimally invasive techniques were used successfully at our institution to minimize the risk of post-operative CSF leak.     

Effect of adhesion boosters on indirect bracket bonding

Objective:To determine the influence of two adhesion boosters on shear bond strength and on the bond failure location of indirectly bonded brackets.Materials and Methods:Sixty bovine incisors were randomly divided into three groups (n  =  20), and their buccal faces were etched using 37% phosphoric acid. In group 1 (control), brackets were indirectly bonded using only Sondhi adhesive. In groups 2 and 3, the adhesion boosters Enhance Adhesion Booster and Assure Universal Bonding Resin, respectively, were applied before bonding with Sondhi. Maximum bond strength was measured with a universal testing machine, and the location of bond failure was evaluated using the Adhesive Remnant Index (ARI). One-way analysis of variance followed by the Tukey test (P < .05) was used to compare the shear bond strength among groups, and the differences in ARI scores were evaluated using the Kruskal-Wallis test (P < .05). The Pearson correlation coefficient was calculated to determine whether there was any correlation between bond strength and ARI scores.Results:The mean shear bond strength in group 3 was significantly higher (P < .01) than in the other groups. Evaluation of the locations of bond failure revealed differences (P < .05) among the three groups. There was a moderate correlation between bond strength and ARI scores within group 3 (r  =  0.5860, P < .01).Conclusion:In vitro shear bond strength was acceptable in all groups. The use of the Assure adhesion booster significantly increased both the shear bond strength of indirectly bonded brackets and the amount of adhesive that remained on the enamel after bracket debonding.     

Analysis of gender effects upon verbal and visual memory performance in adults

This study investigated gender effects on verbal and visual memory performance in normal adults (age range 18-91 years). The subjects were 140 volunteers (70 male, 70 female). Individuals in each male-female pair were matched within three years on age and two years on education. Shipley Vocabulary scores for the groups also were equivalent. Subjects were administered the Continuous Visual Memory Test (CVMT), Visual Reproduction subtest (VR), Verbal Selective Reminding Test (VSRT), and Expanded Paired Associate Test (EPAT). Results revealed no differences between males and females for either the Acquisition or Delayed phases of the CVMT and EPAT. Differences for the Delayed VR task also were not significant. Male-female differences for the Immediate VR task were marginally significant, although the mean difference was less than one point, females consistently outperformed males on the VSRT, particularly in the Acquisition phase. Differences on the Delayed task, while statistically significant, averaged only 12 point.