Periodontal parameters and BANA test in patients with chronic renal failure undergoing hemodialysis

Objectives

The aim of this study was to analyze the periodontal parameters of patients with chronic renal failure.

Material and Methods

The periodontal status of 16 Brazilian patients aged 29 to 53 (41.7±7.2) years with chronic renal failure (CRF) and another matched group of 14 healthy controls with periodontitis was assessed clinically and microbiologically. Probing pocket depth (PPD), gingival recession (GR), dental plaque index (PLI), gingival index (GI), and dental calculus index (CI) were the clinical parameters recorded for the entire dentition (at least 19 teeth), while the anaerobic periodontopathogen colonization in four sites with the highest PPD was evaluated using the BANA test (“PerioScan”; Oral B).

Results

The results for the CRF group and control group, respectively were: PPD: 1.77±0.32 and 2.65±0.53; GR: 0.58±0.56 and 0.51±0.36; PLI: 1.64±0.56 and 1.24±0.67; GI: 0.64±0.42 and 0.93±0.50; CI: 1.17±0.54 and 0.87±0.52. Comparison between groups using the "t" test revealed a significantly increased PPD (p<0.001) in the control group. Comparison of the other clincial parameters by the Mann-Whitney test showed differences only for PLI, which was significantly higher (p<0.05) in the CRF group. Spearman''s test applied to each group showed a positive correlation among all clinical parameters, except for GR (p<0.05). None of the groups showed any correlation between GR and GI, while a significant negative correlation between GR and PPD was observed for the CRF group. The percentage of BANA-positive sites was 35.9% for the CRF group and 35.7% for the control group. The BANA test correlated positively with PPD only in the control group and with GR only in the CRF group.

Conclusions

In spite of a higher PLI and dense anaerobic microbial population even in shallow PPD, patients with CRF exhibited better periodontal conditions than periodontitis patients, which is an evidence of altered response to local irritants.     

Neuroprotective potential of CB1 receptor agonists in an in vitro model of Huntington's disease

Background and purpose:

The therapeutic potential of cannabinoids in Huntington''s disease (HD) has been investigated by several groups with complex and sometimes contrasting results. We sought to examine key points of intersection between cannabinoid receptor 1 (CB₁) signalling, survival and the formation of mutant huntingtin aggregates in HD.

Experimental approach:

Using a simplified pheochromocytoma (PC12) cell model of HD expressing exon 1 of wild-type or mutant huntingtin, we assayed cell death and aggregate formation using high-throughput cytotoxicity and image-based assays respectively.

Key results:

CB₁ activation by HU210 conferred a small but significant level of protection against mutant huntingtin-induced cell death. Pertussis toxin uncoupled HU210 from the inhibition of cAMP, preventing rescue of cell death. Phosphorylation of extracellular signal-regulated kinase (ERK) was also critical to CB₁-mediated rescue. Conversely, treatments that elevated cAMP exacerbated mutant huntingtin-induced cell death. Despite opposing effects on HD cell survival, both HU210 and compounds that elevated cAMP increased the formation of mutant huntingtin aggregates. The increase in aggregation by HU210 was insensitive to Pertussis toxin and UO126, suggesting a G-protein alpha subtype s (G_s)-linked mechanism.

Conclusions and implications:

We suggest that the CB₁ receptor, through G-protein alpha subtype i/o (G_i/o)-linked, ERK-dependent signal transduction, is a therapeutic target in HD. However the protective potential of CB₁ may be limited by promiscuous coupling to G_s, the stimulation of cAMP formation and increased aggregate formation. This may underpin the poor therapeutic efficacy of cannabinoids in more complex model systems and suggest that therapies that are selective for the G_i/o, ERK pathway may be of most benefit in HD.This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x     

生物标志物与非小细胞肺癌治疗结局相关

血管内皮生长因子（VEGF）和可溶性VEGF受体2（sVEGFR-2）由VEGF通路抑制因子所调控,化疗、VEGFR抑制剂或两者联合治疗是否可引起细胞因子和血管生成因子（CAFs）的改变,而这些改变是否又能预示临床获益？     

Femoral Neck Trabecular Bone: Loss With Aging and Role in Preventing Fracture

Hip fracture risk rises 100‐ to 1000‐fold over six decades of age, but only a minor part of this increase is explained by declining BMD. A potentially independent cause of fragility is cortical thinning predisposing to local crushing, in which bone tissue's material disintegrates at the microscopic level when compressed beyond its capacity to maintain integrity. Elastic instability or buckling of a much thinned cortex might alternatively occur under compression. In a buckle, the cortex moves approximately at right angles to the direction of load, thereby distorting its microstructure, eventually to the point of disintegration. By resisting buckling movement, trabecular buttressing would protect the femoral neck cortex against this type of failure but not against crushing. We quantified the effect of aging on trabecular BMD in the femoral neck and assessed its contribution to cortical elastic stability, which determines resistance to buckling. Using CT, we measured ex vivo the distribution of bone in the midfemoral necks of 35 female and 33 male proximal femurs from cases of sudden death in those 20–95 yr of age. We calculated the critical stress σ_cr, at which the cortex was predicted to buckle locally, from the geometric properties and density of the cortical zone most highly loaded in a sideways fall. Using long‐established engineering principles, we estimated the amount by which stability or buckling resistance was increased by the trabecular bone supporting the most stressed cortical sector in each femoral neck. We repeated these measurements and calculations in an age‐ and sex‐matched series of femoral necks donated by women who had suffered intracapsular hip fracture and controls, using histological measurements of cortical thickness to improve accuracy. With normal aging, trabecular BMD declined asymmetrically, fastest in the supero‐lateral one‐half (in antero‐posterior projection) of the trabecular compartment. When viewed axially with respect to the femoral neck, the most rapid loss of trabecular bone occurred in the posterior part of this region (supero‐posterior [S‐P]), amounting to a 42% reduction in women (34% in men) over five decades of adult age. Because local cortical bone thickness declined comparably, age had no significant effect on the relative contributions of cortical and trabecular bone to elastic stability, and trabecular bone was calculated to contribute 40% (in men) and 43% (in women) to the S‐P cortex of its overall elastic stability. Hip fracture cases had reduced elastic stability compared with age‐matched controls, with a median reduction of 49% or 37%, depending on whether thickness was measured histologically or by CT (pQCT; p < 0.002 for both). This effect was because of reduced cortical thickness and density. Trabecular BMD was similar in hip fracture cases and controls. The capacity of the femur to resist fracture in a sideways fall becomes compromised with normal aging because cortical thickness and trabecular BMD in the most compressed part of the femoral neck both decline substantially. This decline is relatively more rapid than that of femoral neck areal BMD. If elastic instability rather than cortical crushing initiates the fracture event, interventions that increase trabecular bone in the proximal femur have great potential to reduce fracture risk because the gradient defining the increase in elastic stability with increasing trabecular BMD is steep, and most hip fracture cases have sufficient trabecular bone for anabolic therapies to build on.     

Foxp3 expression in lesions of the different clinical forms of American tegumentary leishmaniasis

As the diversity in clinical presentation of American tegumentary leishmaniasis (ATL) is determined mainly by the immune response of host, our aim was to evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in lesions of the different clinical forms of ATL. Foxp3⁺ cells were observed in 39·5% (32/81) of the samples and the number of positive cells was low in all the clinical forms. Even presenting a significantly lower number of CD4⁺ T cells, diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). In LCL and MCL, the number of Foxp3⁺ cells correlated positively with the number of apoptotic cells (active caspase-3⁺ cells). A positive correlation was also observed between the expression of active caspase-3 and FasL in these clinical forms. Our data suggest that increased number of Treg cells may be associated to the hyporesponsiveness observed in DCL and also indicate that the apoptosis may be a possible mechanism of action of Foxp3⁺ Treg cell in LCL and MCL. However, further studies are required to better understand the mechanism of action of Treg cell.     

Continent urinary diversions: review of current surgical procedures and radiologic imaging

Continent urinary diversions are currently gaining wide acceptance as alternatives to the ileal conduit following cystectomy for neoplasm or bladder dysfunction. Clean, intermittent catheterization of the reservoir (pouch) at regular intervals obviates the inconvenience of wearing an external stomal appliance. A variety of surgical techniques have been described for continent pouches. These techniques make use of the small bowel alone (Camey and Kock techniques) or a combination of cecum and terminal ileum (Indiana, Mainz, Penn, and King techniques). The optimum pouch protects the upper tracts by prevention of reflux, provides urinary continence, and has sufficient capacity to require catheterization no more frequently than every 3-6 hours. Simplified construction techniques for the commonly encountered pouches are graphically presented, and a method is suggested for the study of continent diversions.     

Increased IL-10 production by stimulated whole blood cultures in primary IgA nephropathy

Most patients with primary IgA nephropathy (IgAN) have a significantly higher memory repertoire of IgA1-producing B lymphocytes in their bone marrow together with high plasma levels of IgA1. The connection between the mucosal immune system and the bone marrow compartment is probably based on traffic of either antigen-presenting cells (APC) or antigen-specific lymphocytes. Cytokines play an important role in the proliferation and differentiation of lymphoid cells. In order to mimic the in vivo situation as much as possible, we assessed cytokine production profiles ex vivo in 23 IgAN patients and matched controls, using lipopolysaccharide (LPS)- or phytohaemagglutinin (PHA)-stimulated whole blood (WB) cultures. Interferon-gamma (IFN-γ), IL-2, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-α) production in culture supernatants were determined by cytokine-specific ELISAs. Compared with controls, PHA-stimulated cultures resulted in significantly higher IL-10 (P < 0.001), IL-2 (P < 0.005) and IFN-γ (P < 0.001) levels in IgAN patients, but no significant differences in TNF-α or IL-6 levels were found. In LPS-stimulated cultures, the only significant difference (P < 0.001) between the two groups was the increased IL-10 production in IgAN patients. The enhanced cytokine production in stimulated WB cultures suggests altered monocyte-related T cell responses in patients with IgAN. Increased IL-10 production may eventually result in an increased number of IgA-producing B lymphocytes in the bone marrow. In addition, high levels of endogenous IL-10 may down-regulate the effector functions of monocytes, or possibly APC in general, and consequently the IgA response at the mucosal level.     

Bisphosphonate associated osteomyelitis of the jaw in patients with bony exposure: prevention,a new way of thinking

Objective

There is strong evidence of a link between the use of systemic bisphosphonates (BPs) and osteonecrosis of the jaw, especially in cancer patients. Among risk factors for BRONJ, tooth extraction and immune suppressive drugs seem to have significant role on bone healing. Therefore, the importance of these parameters in development of BRONJ was reviewed in this retrospective study in two maxillofacial surgery units.

Material and Methods

From 2007 to 2012, 46 patients on bisphosphonate who had developed oral bony lesions participated in this study. The pharmacological exposure, comorbidities, maxillofacial findings, types of treatment and outcome data were collected from clinical and radiological records.

Results

The most frequently used BP was alendronate (67%). Tooth extraction was reported in 61% of patients with BRONJ. Systemic corticosteroids were prescribed in 35 cases (76%) as an adjuvant for BP. Patients on corticosteroids had a lower probability of bony lesion healing (p<0.05) than patients without corticosteroids. Of the 46 patients who underwent conservative treatments, only ten were completely healed (21%).

Conclusions

Beside tooth extraction, corticosteroids were shown to be an implant risk factor for low rate of bone healing and hence the development of BRONJ. The outcome of conservative treatment was uncertain and this emphasizes the importance of prevention.