Association Between VDR FokI Polymorphism and Intervertebral Disk Degeneration

Intervertebral disk degeneration(IDD) is strongly associated with genetic predisposition and environmental susceptibility. Several studies been conducted to investigate the potential association between IDD and Fok I polymorphism located in the gene encoding the vitamin D receptor(VDR), and inconsistent conclusions had been reached among different ethnic populations. In order to assess the association between the Fok I polymorphism and the risk of IDD, we performed a comprehensive and systematic meta-analysis. Candidate articles were retrieved from Pub Med,EMBASE, China National Knowledge Infrastructure(CNKI), and China Biology Medical(CBM) with strict inclusion criteria in January 2015. Among the 54 articles that were retrieved, only eight studies met the inclusion criteria. The pooled data analysis based on allele contrast, homozygote, heterozygote, dominant, and recessive models revealed no significant correlation between the Fok I polymorphism and the risk of IDD. However, when stratified by ethnicity, significant associations were detected for Hispanics based on allele contrast(OR = 1.395, 95% CI = 1.059–1.836,P = 0.018), homozygote(OR = 1.849, 95% CI = 1.001–3.416, P = 0.049), heterozygote(OR = 1.254, 95% CI = 1.049–1.498, P = 0.013), and dominant(OR = 1.742, 95%CI = 1.174–2.583, P = 0.006) models, and for Asians using the dominant model(OR = 1.293,95% CI = 1.025–1.632, P = 0.030), whereas there is no significant association detected for Caucasians. In conclusion, Fok I polymorphism is not generally associated with IDD, but there is increased risk for IDD in Hispanics and Asians carrying Fok I allele T.     

Copeptin as an Indicator of Hemodynamic Derangement and Prognosis in Liver Cirrhosis

Background

Advanced liver cirrhosis is associated with systemic hemodynamic derangement leading to the development of severe complications associated with increased mortality. Copeptin is a stable cleavage product of the precursor of arginine vasopressin, a key-regulator in hemodynamic homeostasis. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. The present study aimed to assess copeptin, both experimentally and clinically, as a potential biomarker of hemodynamic derangement and to evaluate its prognostic significance in cirrhosis.

Materials and Methods

Two studies were executed: 1) in 18 thioacetamide-induced cirrhotic rats and 5 control rats, plasma copeptin and hemodynamic measurements were performed, 2) in 61 cirrhotic patients, serum copeptin concentration was measured in samples collected at time of registration at the waiting list for liver transplantation. In 46 patients, also a second copeptin measurement was performed during follow-up while registered at the waiting list for liver transplantation. To determine the association of serum copeptin and clinical data with outcome, Cox proportional hazard regression analysis and Kaplan Meier analysis were performed.

Results

Plasma copeptin concentration was significantly higher in cirrhotic rats than in controls (1.6 ± 0.5 vs. 0.9 ± 0.1 pmol/L, p< 0.01) and was negatively correlated to the mean arterial blood pressure (r = -0.574, p = 0.013). In cirrhotic patients, serum copeptin concentration was high [11.0 (5.2–24.0) pmol/L] and increased significantly during the time of registration at the waiting list for liver transplantation. MELD and MELD-sodium score were significantly correlated to serum copeptin [MELD: (r = 0.33, p = 0.01), MELD-sodium: (r = 0.29, p = 0.02)], also at time of the second copeptin measurement [MELD and MELD-sodium: r = 0.39, p< 0.01]. In cirrhotic humans, serum copeptin concentration was significantly associated with outcome, independently of the MELD and MELD-sodium score. Patients with a low serum copeptin concentration at time of registration at the liver transplant waiting list had significantly better transplant-free survival rates at 3, 6 and 12 months of follow-up as compared to those with a high serum copeptin concentration (Log-rank: p< 0.01, p< 0.01 and p = 0.02 respectively).

Conclusions

Circulating copeptin levels are elevated in rats and humans with cirrhosis. Copeptin is independently associated with outcome in cirrhotic patients awaiting liver transplantation.     

Time-Resolved Tryptophan Fluorescence as an Indicator of Alterations in Serum Proteins in Melancholic Depression

Biophysics - Abstract—The goal of this work was to search for blood serum parameters that would be associated with the state of patients with mental disorders. Such indicators are needed for...     

Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration

Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol) injected immediately after lesion were analyzed acutely (2 days) by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.     

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

Disc degeneration is the most common cause of back pain in adults and has enormous socioeconomic implications. Conservative management is ineffective in most cases, and results of surgical treatment have not yet reached desirable standards. Biologic treatment options are an alternative to the above conventional management and have become very attractive in recent years. The present review highlights the currently available biologic treatment options in mild and moderate disc degeneration, where a potential for regeneration still exists. Biologic treatment options include protein-based and cell-based therapies. Protein-based therapies involve administration of biologic factors into the intervertebral disc to enhance matrix synthesis, delay degeneration or impede inflammation. These factors can be delivered by an intradiscal injection, alone or in combination with cells or tissue scaffolds and by gene therapy. Cell-based therapies comprise treatment strategies that aim to either replace necrotic or apoptotic cells, or minimize cell death. Cell-based therapies are more appropriate in moderate stages of degenerated disc disease, when cell population is diminished; therefore, the effect of administration of growth factors would be insufficient. Although clinical application of biologic treatments is far from being an everyday practice, the existing studies demonstrate promising results that will allow the future design of more sophisticated methods of biologic intervention to treat intervertebral disc degeneration.     

Trace Element Concentration in Hair Samples as an Indicator of Exposure of Population in the Negev, Israel

The concentration of the toxic elements Ag, As, Cd, Co, Mn, Mo, Pb, Se, and U and the elements Al, Mg, Cu, Fe, and Zn in human hair samples of population living in the north of the Negev Desert in Israel was determined. The study population consisted of three subgroups: Jewish urban population, Bedouin urban population, and Bedouins living in unrecognized villages (the “dispersion”). The main focus is on the differences between these subgroups in an attempt to explore factors responsible for the variation in trace metal contents in hair samples. The results show that the level of several elements, particularly Ag, Mn, and Pb, in the female Bedouin group significantly differed from the other groups in the study. Exploring the reasons for these differences, we concluded that the lifestyle of those women is the main cause. The female Bedouin subgroup is exposed to heavy metals from kitchen utensils, jewelry, and makeup. Therefore, differences in the heavy metal concentration in the hair samples of this group were attributed to the traditional unique lifestyle and social behavior of the females in the Bedouin society.     

氧化应激介导的NF-kB 信号转导通路在椎间盘退变中的作用

椎间盘位于两个椎体之间,在脊柱中发挥着连接、减震和固定作用,其发生退变可以引起一系列椎间盘退变性疾病,是多数 脊柱疾病发病的根本原因,探索椎间盘的退变机制是寻找其治疗措施的前提。椎间盘退变机制十分复杂,其最主要的病理基础是 椎间盘活性细胞减少以及其引起的细胞外基质合成减少和成分的改变,而NF-kB 作为一种普遍存在在真核细胞中的多向性转录 因子,通过多种途径在细胞增殖、分化及凋亡方面起着关键的作用,研究表明,抑制NF-kB信号通路可以有效的缓解椎间盘退变; 而引起NF-kB信号通路的异常激活的因素很多,其中氧化应激是一个重要的因素,同时研究证实在椎间盘退变中存在着氧化损 伤。因此,当年龄、营养、外伤等因素引起的椎间盘细胞中发生氧化应激,进而导致NF-资B信号通路的激活,从而使其转录活性增 高,触发凋亡信号,引起髓核细胞的大量凋亡,使其参与到椎间盘退变中。     

The Nucleus of the Intervertebral Disc from Development to Degeneration

The nucleus of the intervertebral disc in humans shows the mostdramatic changes with age of any cartilaginous tissue. It originatesfrom the notochord. In the foetus and infant, the nucleus containsactively dividing and biosynthetically active notochordal cells.The proteoglycans and other matrix components produced havea high osmotic pressure, imbibe water and maintain a hydratedstructure which, though it has little mechanical strength, hasa high swelling pressure which maintains disc turgor. In somespecies, the notochordal cells and the mucoid nucleus pulposuspersist throughout adult life. However by about 4 yr of agein humans, the notochordal cells have disappeared to be replacedby those of chondrocytic appearance but of unknown origin. Thesecells continue to produce proteoglycans but also synthesizesignificant amounts of collagen. The nucleus becomes firmerand less hydrated and loses its transparent appearance. Thecell density of the adult nucleus is very low with cells occupyingless than 0.5% of tissue volume; each cell thus has to turnover and maintain a large domain of extracellular matrix. Thedensity of living cells decreases with age, possibly becauseof problems with nutrient supply to this large avascular tissue.Proteoglycan concentration also falls, and nucleus hydrationdecreases markedly, the disc discolours and in many cases cleftsand fissures form. In most adults, the disc nucleus degenerateseventually to a stage where it can no longer fulfil its mechanicalrole.     

High YKL-40 Serum Concentration Is Correlated with Prognosis of Chinese Patients with Breast Cancer

This study aimed to investigate the association between serum YKL-40 and prognosis of breast cancer in a Chinese population. Expression of YKL-40 of 120 Chinese patients with breast cancer and 30 controls (benign breast lesions) was measured in tumor tissue by immunohistochemistry and in serum by ELISA. Differences in YKL-40 positivity grouped by specific patients’ characteristics were compared using Pearson Chi-square test for rates of intratumoral staining, one-way ANOVA with a Bonferroni post-hoc comparison, or two-sample t-test for mean YKL-40 serum concentrations. Factors associated with overall survival were identified by univariate and multivariate cox-regression analyses. YKL-40 was elevated in approximately 75% of Chinese patients with breast cancer. A significantly higher percentage of patients with YKL-40 positive tumors had larger tumor size, higher TNM stage, and/or lymph node metastasis. Significantly higher mean YKL-40 serum concentrations were observed in patient subgroups with invasive lobular carcinoma (P<0.0167), higher TNM stage (P<0.001), and positive lymph node metastasis (P<0.001). The estimated mean survival time of patients with YKL-40 positive tumors was significantly shorter than for patients with YKL-40 negative tumors (55.13 months vs 65.78 months, P = 0.017). Multivariable Cox-regression analysis identified a significant association of overall survival time with YKL-40 serum concentration. Patients with YKL-40 positive tumors had significantly shorter disease free survival times than those with YKL-40 negative tumors. We propose that the potential utility of YKL-40 intratumoral staining or serum concentration as a biomarker for breast cancer is greatest within 5 years of diagnosis.     

Calcium as an environmental variable

Abstract. The chemical state of calcium in the soil and the effects, both direct and indirect, which this can have on the growth and distribution of plants are considered. Recent advances in knowledge refer mainy to interactions (between nitrogen source, aluminium and pH, for example) for which there is now experimental evidence and which themselves are influenced by calcium. The impact of physical variables is less marked than first thought although seasonal effects of waterlogging and drought can be critical. It is emphasized that the terms 'calcicole' and 'calcifuge' are generally acceptable in classifying plants according to the degree of calcareousness of the soils in which they occur but only if the wider implications are appreciated.     

Sesn2 Serves as a Regulator between Mitochondrial Unfolded Protein Response and Mitophagy in Intervertebral Disc Degeneration

Mitochondrial unfold protein response (UPR^mt) can induce mitophagy to protect cell from unfold protein. However, how UPR^mt induces mitophagy to protect cell is not yet clear. Herein, Sesn2 was considered to be a key molecule that communicated UPR^mt and mitophagy in the intervertebral disc. Silencing of Sesn2 was able to reverse the protective effects of Nicotinamide riboside (NR) on nucleus pulposus (NP) cells and inhibit mitophagy induced by UPR^mt. UPR^mt upregulated Sesn2 through Eif2ak4/eIF2α/Atf4, and further induced mitophagy. Sesn2 promoted the translocation of cytosolic Parkin and Sqstm1 to the defective mitochondria respectively, thereby enhancing mitophagy. The translocation of cytosolic Sqstm1 to the defective mitochondria was dependent on Parkin. The two functional domains of Sesn2 were necessary for the interaction of Sesn2 with Parkin and Sqstm1. The cytosolic interaction of Sesn2 between Parkin and Sqstm1 was independent on Pink1 (named as PINK1 in human) but the mitochondrial translocation was dependent on Pink1. Sesn2-/- mice showed a more severe degeneration and NR did not completely alleviate the intervertebral disc degeneration (IVDD) of Sesn2-/- mice. In conclusion, UPR^mt could attenuate IVDD by upregulation of Sesn2-induced mitophagy. This study will help to further reveal the mechanism of Sesn2 regulating mitophagy, and open up new ideas for the prevention and treatment of IVDD.     

Basic Fuchsin as an Indicator in Endo's Medium

The writer has made an investigation of various samples of basic fuchsin for use in the Endo medium for differentiating the bacteria of the colon-typhoid group. Various different concentrations of the fuchsin samples have been used in making the media. The conclusions are as follows:

American made fuchsins differ markedly in their alcohol solubility properties. They contain materials which are very readily soluble in 95% alcohol, but which are precipitated by sodium sulphite.

This precipitation may be prevented by increasing the dilution of the fuchsin in alcohol.

In order to secure more dependable results in the use of decolorized basic fuchsin as an indicator in Endo Agar, it is advisable to test the fuchsin in different dilutions in alcohol in order to secure a completely decolorized solution. It is also advisable to carefully test those fuchsins which decolorize only in high dilutions with a known organism in Endo agar before relying on it as a satisfactory indicator for the presence of sewage organisms.     

Fecal Nitrogen Concentration as a Nutritional Quality Indicator for European Rabbit Ecological Studies

Measuring the quality of the nutritional resources available to wild herbivores is critical to understanding trophic regulation processes. However, the direct assessment of dietary nutritional characteristics is usually difficult, which hampers monitoring nutritional constraints in natural populations. The feeding ecology of ruminant herbivores has been often assessed by analyzing fecal nitrogen (FN) concentrations, although this method has been less evaluated in other taxa. This study analyzed the suitability of FN as an indicator of ingesta quality in the European rabbit (Oryctolagus cuniculus), which is a keystone lagomorph species in Mediterranean ecosystems and of great conservation interest. Firstly, domestic O. cuniculus were used to evaluate under experimental conditions the accuracy of total FN and the metabolic FN as diet quality indicators of forages with characteristics similar to those available under natural conditions. Secondly, the accuracy of Near-Infrared Spectroscopy (NIRS) to calculate FN was tested using partial least squares regression. Thirdly, a pilot field study was conducted to monitor FN dynamics from wild O. cuniculus in three different habitats during wet and drought periods. A strong association was found between diet type and total FN and metabolic FN (Pseudo-R² ≥ 0.89). It was also found that NIRS calibrations were accurate for depicting nitrogen concentrations (R² > 0.98 between NIRS and chemical results). Finally, the seasonal FN dynamics measured in the field were consistent with current knowledge on vegetation dynamics and forage limitations in the three habitats. The results support the use of NIRS methods and FN indices as a reliable and affordable approach to monitoring the nutritional quality of rabbit habitats. Potential applications include the assessment of the mechanistic relationships between resource limitations and population abundance, e.g., in relation to natural drought cycles and to habitat interventions aimed at reinforcing rabbit populations.     

Calcium Intake and Serum Concentration in Relation to Risk of Cardiovascular Death in NHANES III

Background

Evidence for an association between calcium intake and risk of cardiovascular death remains controversial. By assessing dietary intake, use of supplements, and serum levels of calcium, we aimed to disentangle this link in the third National Health and Nutrition Examination Survey (NHANES III).

Methods

Mortality linkage of NHANES III to death certificate data for those aged 17 years or older (n = 20,024) was used to estimate risk of overall cardiovascular death as well as death from ischemic heart disease (IHD), acute myocardial infarction (AMI), heart failure (HF), and cerebrovascular disease (CD) with multivariate Cox proportional hazards regression analysis.

Results

About 10.0% of the population died of cardiovascular disease and the majority (5.4%) died of IHD. There was increased risk of overall CVD death for those in the bottom 5% of serum calcium compared to those in the mid 90% (HR: 1.51 (95% CI: 1.03–2.22)). For women there was a statistically significant increased risk of IHD death for those with serum calcium levels in the top 5% compared to those in the mid 90% (HR: 1.72 (95%CI: 1.13–2.61)), whereas in men, low serum calcium was related to increased IHD mortality (HR: 2.32 (95% CI 1.14–3.01), P_interaction: 0.306). No clear association with CVD death was observed for dietary or supplemental calcium intake.

Conclusions

Calcium as assessed by serum concentrations is involved in cardiovascular health, though differential effects by sex may exist. No clear evidence was found for an association between dietary or supplementary intake of calcium and cardiovascular death.