Alternative sources of neurons and glia from somatic stem cells

Stem cell populations have been shown to be extremely versatile: they can generate differentiated cells specific to the tissue in which they reside and descendents that are of different germ layer origin. This raises the possibility of obtaining neuronal cells from new biological source of the same adult human subjects. In this study, we found that epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) cooperated to induce the proliferation, self-renewal, and expansion of neural stem cell-like population isolated from several newborn and adult mouse tissues: muscle and hematopoietic tissues. This population, in both primary culture and secondary expanded clones, formed spheres of undifferentiated cells that were induced to differentiate into neurons, astrocytes, and oligodendrocytes. Brain engraftment of the somatic-derived neural stem cells generated neuronal phenotypes, demonstrating the great plasticity of these cells with potential clinical application.     

Oral streptococcal strains isolated from odontogenic infections and their susceptibility to antibiotics

The aim of this study was to identify at species level and to investigate the antibiotic susceptibility of oral streptococcal strains isolated from 100 pus samples collected from Romanian patients with different odontogenic infections. The isolates were identified at species level using the Rapid ID 32 STREP system and their susceptibility was testing by the Etest, against: penicillin G, ampicillin, erythromycin, clindamycin and tetracycline. For the investigation of erythromycin resistance phenotype the disk diffusion test was used. The isolates belonged to several species, with Streptococcus anginosus and Streptococcus oralis predominating. Reduced susceptibility to beta-lactam antibiotics was found only among the isolates belonging to S. mitis and S. sanguinis groups. Resistance to erythromycin was detected among all species, except for: S. constellatus, S. intermedius and S. gordonii, and the M phenotype was established, while resistance to tetracycline was detected within all species but S. gordonii. In contrast, clindamycin was fully active. As most odontogenic infections are mixed infections, often involving strictly anaerobic bacteria, which are frequently beta-lactamase producers, the association of a penicillin and a beta-lactamase inhibitor, like Amoxiclav, is recommended when the antimicrobial treatment is necessary.     

Cam morphology and inguinal pathologies: is there a possible connection?

Background

To analyse the prevalences of the cam and pincer morphologies in a cohort of patients with groin pain syndrome caused by inguinal pathologies.

Materials and methods

Forty-four patients (40 men and 4 women) who suffered from groin pain syndrome were enrolled in the study. All the patients were radiographically and clinically evaluated following a standardised protocol established by the First Groin Pain Syndrome Italian Consensus Conference on Terminology, Clinical Evaluation and Imaging Assessment in Groin Pain in Athlete. Subsequently, all of the subjects underwent a laparoscopic repair of the posterior inguinal wall.

Results

The study demonstrated an association between the cam morphology and inguinal pathologies in 88.6% of the cases (39 subjects). This relationship may be explained by noting that the cam morphology leads to biomechanical stress at the posterior inguinal wall level.

Conclusions

Athletic subjects who present the cam morphology may be considered a population at risk of developing inguinal pathologies.

Level of evidence

Level IV, Observational cross-sectional study.

     

Intravenous iron increases labile serum iron but does not impair forearm blood flow reactivity in dialysis patients

BACKGROUND: There are concerns about adverse vascular effects of intravenous iron by inducing oxidative stress. We therefore examined the effect of a single high dose of intravenous iron on endothelial function and biochemical markers of iron homeostasis. METHODS: In a randomized, placebo-controlled, double-blind, parallel-group study, forearm blood flow (FBF) was assessed by strain-gauge plethysmography in 38 peritoneal dialysis patients before and after a single intravenous infusion of 300 mg iron sucrose. RESULTS: Iron infusion increased total (Delta 601 microg/100 mL, CI 507, 696) and non-transferrin-bound iron (Delta 237.2 micromol/L, CI 173.6, 300.8) approximately 10-fold, as well as redox-active iron nearly five-fold (Delta 0.76 micromol/L, CI 0.54, 0.98). After iron infusion basal FBF was 59% higher than after placebo. FBF response to acetylcholine before and after iron infusion was 263 +/- 32% and 310 +/- 33%, corresponding to 304 +/- 43% and 373 +/- 29% in the placebo group, respectively. Before and after iron or placebo infusion, glyceryl-trinitrate increased resting FBF to 232 +/- 22% and 258 +/- 21% in the iron group, and to 234 +/- 18% and 270 +/- 30% in the placebo group. L-N-monomethyl-arginine decreased FBF to 70 +/- 4% and 72 +/- 3% before and after iron, and to 74 +/- 4% and 73 +/- 4% before and after placebo infusions, respectively. Despite higher basal FBF after iron infusion, absolute and relative FBF changes in response to vasoactive substances were not significantly different between iron and placebo groups. CONCLUSION: Our data suggest that 300 mg intravenous iron sucrose has a vasodilatory effect, but does not impair vascular reactivity in dialysis patients, despite a significant increase in non-transferrin-bound and redox-active iron.     

Bone repair following bone grafting hydroxyapatite guided bone regeneration and infra-red laser photobiomodulation: a histological study in a rodent model

The aim of the investigation was to assess histologically the effect of laser photobiomodulation (LPBM) on a repair of defects surgically created in the femurs of rats. Forty-five Wistar rats were divided into four groups: group I (control); group II (LPBM); group III (hydroxyapatite guided bone regeneration; HA GBR); group IV (HA GBR LPBM). The animals in the irradiated groups were subjected to the first irradiation immediately after surgery, and it was repeated every day for 2 weeks. The animals were killed 15 days, 21 days and 30 days after surgery. When the groups irradiated with implant and membrane were compared, it was observed that the repair of the defects submitted to LPBM was also processed faster, starting from the 15th day. At the 30th day, the level of repair of the defects was similar in the irradiated groups and those not irradiated. New bone formation was seen inside the cavity, probably by the osteoconduction of the implant, and, in the irradiated groups, this new bone formation was incremental. The present preliminary data seem to suggest that LPMB therapy might have a positive effect upon early wound healing of bone defects treated with a combination of HA and GBR.     

Effect of cervical dynamics on adjacent segment degeneration after anterior cervical fusion with cages

The objective of this study is to evaluate the effect of anterior cervical discectomy and fusion (ACDF) on the motion of the cervical spine and dynamic stress (tendency to kyphosis) on adjacent segments and on the overall spinal alignment which may predispose to symptomatic disc diseases at other levels. Twenty consecutive patients underwent ACDF with a mean follow-up of 28 months (range 13-38). Preoperative and postoperative clinical assessments were done by using the neck disability index (NDI) and the Japanese Orthopedic Association (JOA) score. In all cases, at the last follow-up control, a neuro-radiographic assessment [cervical spine static and dynamic X-ray and magnetic resonance imaging (MRI)] was done. The angle of the operated disc space, the disc space angle of contiguous segments, and their range of motion (ROM) and the kyphotic Cobb angle (C2-7) were measured by computer software. The study was done at Sant'Andrea Hospital, Rome, Italy in the period from November 2003 to November 2005. We observed that: the mean Cobb angle improved significantly (p < 0.001) from 3.4 degrees (kyphosis) to postoperative 14.5 degrees . This normalization of angle showed a direct effect on improvement of myelopathic patients, but it had a statistically nonsignificant effect on adjacent segments degeneration (ASD). The mean segmental ROM of adjacent segments did not show significant instability. The mean was 11.1 degrees at upper and 10.2 degrees at lower levels (close to normal). In six cases, the ROM was higher than normal: five of these patients demonstrated symptomatic adjacent segment pathology. Postoperative improvement of mean JOA and NDI scores was statistically significant (p < 0.001). Anyway, symptomatic ASD was observed in five patients (20%): in four of them, the higher disc spaces and in one, the lower disc spaces were involved. In four cases, the preoperative MRI showed slight and asymptomatic disc degeneration at the same levels involved subsequently. This ASD was significantly related to the increased ROM at the segments involved. Follow-up X-rays showed solid fusion with absence of movement in all but one case (at 13-month follow-up), who showed slight movement in the operated level in spite of clinical improvement. The follow-up MRI showed, in all cases, good decompression in the treated levels. Compensatory increase in ROM of the contiguous motion segments in patients subjected to ACDF may lead to ASD especially in those cases with asymptomatic adjacent subclinical degenerative disease. If these preliminary results will be confirmed by larger series, it could be reasonable in young selected patients with soft disc herniation to adopt total disc arthroplasty instead of fusion after cervical micro-discectomy.     

Metabolic consequences of physical inactivity.

Physical inactivity is associated with alteration of normal physiologic processes leading to muscle atrophy, reduced exercise capacity, insulin resistance, and altered energy balance. Bed rest studies in human beings using stable isotopes of amino acids indicate that muscle unloading decreases the turnover rates of muscle and whole-body proteins, with a prevailing inhibition of protein synthesis. In the fasting state, muscle and whole-body nitrogen loss was not accelerated during bed rest. In experimental postprandial states, the amino acid-mediated stimulation of protein synthesis was impaired, whereas the ability of combined insulin and glucose infusion to decrease whole-body proteolysis was not affected by muscle inactivity. Thus, an impaired ability of protein/amino acid feeding to stimulate body protein synthesis is the major catabolic mechanism for the effect of bed rest on protein metabolism. This suggests that a protein intake level greater than normal could be required to achieve the same postprandial anabolic effect during muscle inactivity. Metabolic adaptation to muscle inactivity also involves development of resistance to the glucoregulatory action of insulin, decreased energy requirements, and increased insulin and leptin secretion. These alterations may lead to the development of the metabolic syndrome that is defined as the association of hyperinsulinemia, dyslipidemia, hypertension, hyperglycemia, and abdominal obesity. This cluster of metabolic abnormalities is a risk factor for coronary artery disease and stroke. Evidence indicates that exercise training programs may counteract all of these abnormalities both in healthy sedentary subjects and in patients affected by a variety of chronic disease states.     

Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B in kidney transplant recipients

BACKGROUND: Currently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B(12), folate, or total homocysteine (tHcy). METHODS: In a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B(12), folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes. RESULTS: The allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N= 72) or homozygosity (N= 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B(12) (P= 0.33) or tHcy (P= 0.70), but a borderline association with higher folate concentrations was detected (Deltafolate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P= 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B(12) concentrations. CONCLUSION: Higher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B(12) in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes.     

p16 Is upregulated in proliferative inflammatory atrophy of the prostate

BACKGROUND: Proliferative inflammatory atrophy (PIA) of the prostate is a common histological finding that has been postulated to be associated with prostate cancer. We examine PIA lesions for the expression of p16/CDKN2, a cyclin-dependent kinase inhibitor frequently altered in prostate cancer. METHODS: Within tissues from two independent patient populations ("Test Set" and "Validation Set") undergoing radical prostatectomy, PIA lesions were identified and subjected to immunohistochemical staining for p16. Atrophic epithelial cells and regional normal epithelium were scored for the extent of p16 staining. In the Test Set, staining was also performed for the proliferation marker Ki-67. Double label immunofluorescence was employed to co-localize staining for p16 and Ki-67. RESULTS: p16 expression was elevated in PIA in both data sets compared to normal epithelium (mean percent of cells staining positive in PIA = 11.1%-16.2%; mean percent of cells staining positive in normal = 0.6%-1.3%) (P = 0.0001). As expected from prior studies, the mean Ki-67 index was higher in PIA lesions (mean 8.2% staining positive) versus normal epithelium (mean 1.9% staining positive) (P = 0.0001), and the extent of staining for p16 correlated with Ki-67 (r = 0.7, P < 0.0001). However, co-localization immunofluorescent studies did not demonstrate staining for nuclear p16 and Ki-67 in the same cells. CONCLUSIONS: Increased p16 expression accompanies increased cell proliferation in PIA lesions of the prostate. Yet, on the individual cell level, the upregulation of p16 in PIA lesions appears to represent a non-proliferative stress response, possibly to oxidative damage.