Insulinemic and Inflammatory Dietary Patterns and Risk of Prostate Cancer

BackgroundHyperinsulinemia and inflammation are inter-related pathways that link diet with the risk of several chronic diseases. Evidence suggests that these pathways may also increase prostate cancer risk.ObjectiveTo determine whether hyperinsulinemic diet and inflammatory diet are associated with prostate cancer incidence and mortality.Design, setting, and participantsWe prospectively followed 41 209 men in the Health Professionals Follow-up Study (1986–2014). Scores for two validated dietary patterns were calculated from food frequency questionnaires at baseline and updated every 4 yr.Outcome measurements and statistical analysisTotal, advanced, and lethal prostate cancer outcomes were assessed. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were determined for associations between two empirical hypothesis-oriented dietary patterns—empirical dietary index for hyperinsulinemia and empirical dietary inflammatory pattern—and prostate cancer risk estimated using Cox proportional hazard regression.Results and limitationsDuring 28 yr of follow-up, 5929 incident cases of total prostate cancer, including 1019 advanced and 667 fatal, were documented. In multivariable-adjusted models, there was a 7% higher risk of advanced prostate cancer (HR: 1.07; 95% CI: 1.01–1.15) and a 9% higher risk of fatal prostate cancer (HR: 1.09; 95% CI: 1.00–1.18) per standard deviation (SD) increase in the hyperinsulinemic diet. When stratified by age, the hyperinsulinemic diet was associated with only earlier-onset aggressive prostate cancer (men under 65 yr), with per SD HRs of 1.20 (95% CI: 1.06–1.35) for advanced, 1.22 (1.04–1.42) for fatal, and 1.20 (1.04–1.38) for lethal. The inflammatory diet was not associated with prostate cancer risk in the overall study population, but was associated with earlier-onset lethal prostate cancer (per SD increase HR: 1.16; 95% CI: 1.00–1.35).ConclusionsHyperinsulinemia and inflammation may be potential mechanisms linking dietary patterns with the risk of aggressive prostate cancer, particularly earlier-onset disease.Patient summaryAvoiding inflammatory and hyperinsulinemic dietary patterns may be beneficial for the prevention of clinically relevant prostate cancer, especially among younger men.     

Interaction between COMT haplotypes and cannabis in schizophrenia: a case-only study in two samples from Spain

Cannabis use is one of the environmental factors with more solid evidence contributing to schizophrenia risk, especially in genetically susceptible individuals. One of the genes that may interact with cannabis is COMT, although available data are scarce. Here, we present a case-only study of the putative COMT-cannabis interaction in schizophrenia. Two Spanish samples from Santiago de Compostela and Valencia were screened for cannabis use. One hundred and fifty five individuals from a total of 748 patients were identified as cannabis users. Five SNPs in COMT, defining three common functional haplotypes with different enzymatic activities, were genotyped and analyzed for association at the SNP, haplotype and genotype levels. An association was detected between cannabis use and low activity variants (P<0.01) in the joint analysis and results were consistent between the two samples. Schizophrenic subjects homozygous for the Met allele at rs4680 doubled the probability of lifetime prevalence of cannabis use in comparison to Val homozygous (Mantel-Haenszel OR=2.07, 95% CI: 1.27-3.26, P=0.0031, in the combined sample). These data are in contrast to those from Caspi et al. (Biol. Psychiatry 57 (2005)1117-1127) who found association between schizophrenia/schizophreniform disorder and homozygosity at the high activity Val variant of rs4680. The results of our study are discussed in the context of previous findings, suggesting the involvement of COMT polymorphisms in the association between cannabis use and schizophrenia as well as the existence of additional factors mediating this association. However, further research is needed to confirm the COMT-cannabis interaction.     

Critical diameter of apical foramen and of file size using the Root ZX apex locator: an in vitro study

Introduction

An evaluation was made of the accuracy of the Root ZX apex locator (J. Morita Corp, Tokyo, Japan) in widened foramina, considering the existing controversy over this issue in the literature.

Methods

Ten single-root teeth were embedded in an alginate mold. The foramina were widened from 0.6 mm to 1.0 mm. The measurements were taken with all possible file sizes ≥#10. The statistical accuracy of the Root ZX was calculated for the different diameters and for the influence of file size.

Results

The accuracy of the Root ZX apex locator with a range of error of ±0.5 mm was 87% in an apical foramen size of 0.6 mm and 84% using files size 45 or larger in an apical foramen size of 0.7 mm. With a tolerance of ±1 mm, the accuracy was 99% in an apical foramen size of 0.6 mm, 98% using files size 45 or larger in an apical foramen size of 0.7 mm, and 95% using files size 70 or larger in an apical foramen size of 0.8 mm. In the rest, accuracy was not certain. The measurements taken with smaller files were shorter. There were no cases of overestimation of the working length.

Conclusions

The Root ZX apex locator was accurate for an apical size of 0.6 mm, independently of the file size; between 0.7 to 0.8 mm, we should adjust the files to the foramen, whereas above size 0.9 mm the locator is not accurate. The results show that the accuracy of this electronic apex locator is gradually lost as the foramen widens. Considering the stable conditions of in vitro studies, our findings advise caution in clinical application of the locator.     

Vitamin D deficiency in South Europe: effect of smoking and aging

The main source of vitamin D is synthesis in the skin during exposure to ultraviolet radiation. The existence of photoaggravated diseases and the increasing incidence of skin cancer have prompted recommendations to avoid the sun. Here, we study the status of vitamin D in a healthy population and its relation to their habits of sun exposure. To do so, we designed a cross-sectional study that included 177 healthy people. We analyzed parameters about demographic data, sun exposure, and protection habits and estimated vitamin D dietary intake. We performed blood tests to measure serum 25-hydroxyvitamin D [25(OH)D], calcium, phosphorus, and intact parathyroid hormone. Mean levels (± standard deviation) of 25(OH)D were 24.0 (± 8.5) ng/ml. Seventy-six percent of the population did not reach recommended levels of vitamin D (30 ng/ml), including 4.5% who were vitamin D deficient (< 10 ng/ml). Levels were higher in young people (P = 0.04) and those with more sun exposure (P = 0.04). Smoking was associated with an increased risk of hypovitaminosis D (odds ratio, 1.8; 95% confidence interval, 1.00-3.35). On the basis of our findings, we should consider the risk of hypovitaminosis when we recommend sun avoidance, especially in some risk groups, because the sun is the most important source of this vitamin.     

Comparison of the Cozart DDS 801 on-site drug test device and gas chromatography/mass spectrometry (GC/MS) confirmation results of cannabis and cocaine in oral fluid specimens

Driving under the influence of drugs (DUID) is a problem around the world. The objective of this study is to assess the reliability of the oral fluid screening device the Cozart DDS 801 by comparing the on-site results with confirmatory gas chromatography/mass spectrometry (GC/MS) oral fluid analysis. The study was carried out in Catalonia (Spain) with a sample of 2180 oral fluid specimens taken from subjects suspected of driving under the influence of drugs of abuse, and collected by police officers during 2009–2010. Statistical parameters of the tests were determined for cannabis and cocaine. The sensitivity, specificity, predictive positive value, predictive negative value, likelihood positive ratio and likelihood negative ratio for cocaine were 92%, 90%, 95%, 85%, 9.44, and 0.09 respectively. Sensitivity, specificity, predictive positive value, predictive negative value, likelihood positive ratio and likelihood negative ratio for cannabis were 87%, 86%, 94%, 73%, 6.15 and 0.6 respectively. Accuracy was 91% for cocaine and 86% for cannabis. The Cozart DDS 801 drug test system is a simple to use screening tool for cocaine and cannabis in oral fluid, at initial screening cut-off established by the manufacturer, confirmed with a GC/MS analysis. The system has demonstrated its acceptable performance.     

Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients

Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2–20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 ± 0.39 g/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2–4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatemnt of CMV retinitis.Abbreviations AIDS acquired immunodeficiency syndrome - AZT zidovudine - CMV cytomegalovirus - GCV ganciclovir     

Promising results of the chaperone effect caused by iminosugars and aminocyclitol derivatives on mutant glucocerebrosidases causing Gaucher disease

Gaucher disease is an autosomal recessive disorder. It is characterized by the accumulation of glucosylceramide in lysosomes of mononuclear phagocyte system, attributable to acid β-glucosidase deficiency. The main consequences of this disease are hepatosplenomegaly, skeletal lesions and, sometimes, neurological manifestations. At sub-inhibitory concentrations, several competitive inhibitors act as chemical chaperones by inducing protein stabilization and increasing enzymatic activity. Here we tested two iminosugars (NB-DNJ and NN-DNJ) and four aminocyclitols with distinct degrees of lipophilicity as pharmacological chaperones for glucocerebrosidase (GBA). We report an increase in the activity of GBA using NN-DNJ, NB-DNJ and aminocyclitol 1 in stably transfected cell lines, and an increment with NN-DNJ and aminocyclitol 4 in patient fibroblasts. These results on specific mutations validate the use of chemical chaperones as a therapeutic approach for Gaucher disease. However, the development and analysis of new compounds is required in order to find more effective therapeutic agents that are active on a broader range of mutations.     

The action of Lonomin V (Lonomia achelous) on fibronectin functional properties

Lonomia achelous caterpillar, Lepidoptera distributed along some South American countries, induces a hemorrhagic syndrome in people who come into contact with its bristles. A clinical characteristic in these patients is that fresh healed wounds are re-opened and bleed. In order to explain this symptomatology, we evaluated the effect of Lonomin V (a protein isolated from L. achelous hemolymph), on some functional properties of fibronectin, which in turn plays an important role in the hemostasis. The effect of Lonomin V on fibronectin was studied by SDS-PAGE in reduced condition, binding to gelatin and heparin, crosslinking to fibrin and platelet adhesion. Formation of degradation products of 120, 66, 50, 40 and 29 kDa, some of which retain affinity to heparin and gelatin were observed; however, the fibronectin degradation fragments presented a significant decrease of crosslinking capacity to fibrin and platelet adhesion, suggesting that the proteolysis of fibronectin by Lonomin V induces changes in its crosslinking sites and on platelet receptors. These findings might partially explain the wound dehiscence observed in the patients. Due to its effect on adhesive proteins with concomitant impairment of some functional properties, Lonomin V might be useful for cellular adhesion studies involved in hemostasis such as platelet adhesion.     

The AT₁ angiotensin II receptor blockade attenuates the development of amphetamine-induced behavioral sensitization in a two-injection protocol

It has been shown that a single exposure to amphetamine is sufficient to induce long‐term behavioral, neurochemical, and neuroendocrine sensitization in rats. Dopaminergic neurotransmission in the nucleus accumbens and the caudate‐putamen plays a critical role in the addictive properties of drugs of abuse. Angiotensin (Ang) II receptors are found on the soma and terminals of mesolimbic dopaminergic neurons and it has been shown that Ang II acting through its AT₁ receptors facilitates dopamine release. The hypothesis was tested that Ang II AT₁ receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine and that such changes are related to the development of behavioral and neurochemical sensitization. For this purpose, the study examined the expression of amphetamine‐enhanced (0.5 mg kg⁻¹ i.p.) locomotor activity in animals pretreated with candesartan, an AT₁ blocker, (3 mg kg⁻¹ p.o × 5 days), 3 weeks after an amphetamine injection (5 mg kg⁻¹ i.p.). Dopaminergic hyperreactivity was tested by measuring the 3H‐DA release in vitro from caudate‐putamen and nucleus accumbens slices, induced by K⁺ stimulus. It was confirmed the behavioral sensitization in the two‐injection protocol and candesartan pretreatment attenuate this response. It was also found that AT₁ blockade pretreatment did not affect the locomotor response to dopamine agonists. In respect to the neurochemical sensitization tested using ex vivo 3H‐DA release experiments it was found that AT₁ receptor pretreatment blunted the enhanced response induced by K⁺ stimulus. The results support the idea that the development of neuroadaptive changes induced by amphetamine involves brain AT₁ Ang II receptor activation. Synapse, 2011. © 2010 Wiley‐Liss, Inc.