Comparison of biochemical effects of statins and fish oil in brain: the battle of the titans

Neural membranes are composed of glycerophospholipids, sphingolipids, cholesterol and proteins. The distribution of these lipids within the neural membrane is not random but organized. Neural membranes contain lipid rafts or microdomains that are enriched in sphingolipids and cholesterol. These rafts act as platforms for the generation of glycerophospholipid-, sphingolipid-, and cholesterol-derived second messengers, lipid mediators that are necessary for normal cellular function. Glycerophospholipid-derived lipid mediators include eicosanoids, docosanoids, lipoxins, and platelet-activating factor. Sphingolipid-derived lipid mediators include ceramides, ceramide 1-phosphates, and sphingosine 1-phosphate. Cholesterol-derived lipid mediators include 24-hydroxycholesterol, 25-hydroxycholesterol, and 7-ketocholesterol. Abnormal signal transduction processes and enhanced production of lipid mediators cause oxidative stress and inflammation. These processes are closely associated with the pathogenesis of acute neural trauma (stroke, spinal cord injury, and head injury) and neurodegenerative diseases such as Alzheimer disease. Statins, the HMG-CoA reductase inhibitors, are effective lipid lowering agents that significantly reduce risk for cardiovascular and cerebrovascular diseases. Beneficial effects of statins in neurological diseases are due to their anti-excitotoxic, antioxidant, and anti-inflammatory properties. Fish oil omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have similar anti-excitotoxic, antioxidant and anti-inflammatory effects in brain tissue. Thus the lipid mediators, resolvins, protectins, and neuroprotectins, derived from eicosapentaenoic acid and docosahexaenoic acid retard neuroinflammation, oxidative stress, and apoptotic cell death in brain tissue. Like statins, ingredients of fish oil inhibit generation of beta-amyloid and provide protection from oxidative stress and inflammatory processes. Collective evidence suggests that antioxidant, anti-inflammatory, and anti-apoptotic properties of statins and fish oil contribute to the clinical efficacy of treating neurological disorders with statins and fish oil. We speculate that there is an overlap between neurochemical events associated with neural cell injury in stroke and neurodegenerative diseases. This commentary compares the neurochemical effects of statins with those of fish oil.     

Oral Specific Desensitization in Food-Allergic Children

The possibility of obtaining oral desensitization in patients with food allergy is still a matter of debate. We decided to evaluate the safety and efficacy of standardized protocols for oral desensitization with the most common food allergens. Forty-two children (ages up to 16 years) diagnosed as affected by food allergy (on the basis of clinical history, skin prick tests, measurement of specific IgE, and double-blind, placebo-controlled food challenge) underwent a sublingual-oral desensitizing treatment according to new standardized protocols. The control group consisted of 10 patients who followed an elimination diet. The treatment was successfully completed by 85.7% of the patients. Specific IgE showed a significant decrease, while specific IgG₄ showed a significant increase, in all treated patients. The immunological modifications observed in our patients lead us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory and insect sting allergy.     

Glial cell line-derived neurotrophic factor in Purkinje cells of adult zebrafish: An autocrine mode of action?

Glial cell line-derived neurotrophic factor (GDNF) has a neuroprotective role in Purkinje cells of cerebellum, promoting the survival and the differentiation of these cells. Its signalling is mediated by a receptorial complex GFRalpha1/RET. In the brain of adult zebrafish (Danio rerio) we previously investigated GDNF expression and localization, but no data exist regarding GFRalpha1 and RET presence. Thus, the present study was designed to clarify the morphological relation between GDNF and its receptorial complex GFRalpha1/RET immunoreactivity in the cerebellum of adult zebrafish. The expression of gdnf, GFRalpha1 and ret genes was demonstrated in adult zebrafish cerebellum by a standard RT-PCR. The distribution of GDNF and its receptorial complex GFRalpha1/RET was examined by single and double immunocytochemical stainings. In the valvula and corpus cerebelli GDNF, GFRalpha1 and RET immunoreactivity was seen co-localized in Purkinje cells, identified morphologically and by using an antiserum against a specific marker for these cells, aldolase C enzyme. In the vestibulolateralis lobe, Purkinje neurons were lacking in both the eminentiae granulares and medial caudal lobe. These results demonstrated the expression of the GDNF receptorial complex in adult zebrafish cerebellum and suggest an autocrine mode of action of GDNF in Purkinje cells.     

Characterization of three novel β-defensin antimicrobial peptides in rainbow trout (Oncorhynchus mykiss)

An initial bioinformatics investigation followed by cloning and sequencing analysis, has led to the identification of three novel members (omDB-2, omDB-3, omBD-4) of the β-defensin family in rainbow trout (Oncorhynchus mykiss). The contiguous sequences could be translated to give predicted peptides of 62 (omDB-2), 63 (omDB-3) and 68 (omDB-4) amino acids (aa) in length, with mature peptides of 43 (omDB-2), 39 (omDB-3) and 42 (omDB-4) aa, with no obvious proregion present. Analysis of the gene organization found that all three new genes contained three exons divided by two introns, as seen in defensin genes of other fish species. Constitutive expression of all the trout defensins was detected by RT-PCR in a wide range of mucosal and systemic tissues from healthy fish, with omDB-3 and omDB-4 showing the highest expression levels. Following bacterial challenge in vivo, the defensin genes were induced at the three mucosal sites examined (skin, gill, gut), with levels of omDB-2 and omDB-3 increased some 16-fold in gut and gill respectively. Using polyinosinic polycytosinic RNA (polyI:C) as a viral mimic, all of the four trout β-defensin genes were induced in head kidney primary leucocyte cultures at 4 h post-stimulation, with omDB-1 and omDB-3 particularly highly expressed. These data suggest that β-defensins are likely an important component of the innate defences of fish, and reveal an added level of antimicrobial peptide complexity in fish to that known previously.     

Molecular and pharmacological characterization of the melanocortin type 1 receptor in the sea bass

Melanocortin 1 receptor (MC1R) plays a key role in the physiology of the vertebrate pigment system. Point mutations producing hyperactive or inactive receptors result in darkening or paling effects, respectively. We report the molecular and pharmacological characterization, as well as the tissue expression pattern, of the sea bass Mc1r. Similar to other MC1Rs, the sea bass gene is highly polymorphic and nine DNA polymorphisms, seven of them involving an amino acid substitution, were detected. SbMc1r is mainly expressed in the testis, fat and liver with moderate levels in the ventral and dorsal skin. The sea bass receptor was activated by all the melanocortins tested, with ACTH showing the lowest efficiency. The acetylation level of the MSH isoforms seems to be critical for the effectively of the agonist. Agouti-related protein (AGRP) drastically inhibited the basal activity of the receptor in vitro, as an inverse agonist does, but only in the presence of phosphodiesterase inhibitors. This observation suggests that sbMc1r is constitutively activated and inversely regulated by AGRP, which is expressed in the skin of different fish species.     

Heavy Metal Contaminants in Tissues of the Garfish, <Emphasis Type="Italic">Belone belone</Emphasis> L., 1761, and the Bluefish, <Emphasis Type="Italic">Pomatomus saltatrix</Emphasis> L., 1766, from Turkey Waters

Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. Fish samples were collected through the coastal waters of Turkey and the contents of cadmium, cobalt, chrome, copper, iron, manganese, nickel, zinc and lead in the liver and muscle tissues were determined. Among the metals analyzed, copper, zinc and iron were the most abundant in the different tissues while cadmium and lead were the least abundant both in Belone belone and Pomatomus saltatrix. Metal concentrations in muscles of fish species were found 0.01–0.38 mg kg⁻¹ for cadmium, 0.01–0.53 mg kg⁻¹ for cobalt, 0.05–1.87 mg kg⁻¹ for chromium, 0.21–5.89 mg kg⁻¹ for copper, 9.99–43.3 mg kg⁻¹ for iron, 0.14–1.33 mg kg⁻¹ for manganese, 0.06–4.70 mg kg⁻¹ for nickel, 0.09–0.81 mg kg⁻¹ for lead, 3.85–15.9 mg kg⁻¹ for zinc, respectively. Regional changes in metal concentration were observed in the tissues of both species, but these variations may not influence consumption advisories.     

Fish and shellfish consumption estimates and perceptions of risk in a cohort of occupational and recreational fishers of the Chesapeake Bay

Exposure to persistent, bioaccumulating substances, through the consumption of contaminated fish is of concern in human populations. Consumption may be particularly high for subsistence, commercial, and recreational fishers, so it is important to obtain accurate consumption estimates to assess risks in these groups. The objectives of the work reported here were: to obtain estimates of fish and shellfish consumption (meals and portion size) in an occupational cohort; to determine what percentage of the consumption was from local fish; to evaluate reliability of two methods of reporting fish and shellfish consumption; and to examine risk perceptions in relation to consumption. Subjects included 99 recreational and occupational fishers in the Chesapeake Bay area, Virginia, who were recruited for a cohort study of estuary-associated syndrome. Subjects reported average fish and shellfish consumption (all species) on a weekly, monthly or yearly basis, and were asked species-specific information, which was summed. The median number of fish meals consumed a year was significantly different depending on the method used, 52 (interquartile range, IQR:24-104) (average method) and 65 (IQR:30-117) (sum of species-specific), respectively. Shellfish estimates were 24 (IQR:12-52) (average) and 47 (IQR:31-84) (sum) meals a year. Of those who consumed fish, participants reported an average meal size of 8.9±3.38 oz. (median 8 oz, range 4-16) with close to 70% of fish consumed self-caught and 50% from Virginia waters. Using multiple regression, occupation, and risk perceptions were found to be significantly correlated with fish consumption levels, and consumption of fish from locations under advisory.     

Temporal changes in PCB and DDE levels among a cohort of frequent and infrequent consumers of Great Lakes sportfish

A variety of environmentally persistent contaminants of the Great Lakes Basin are able to bioaccumulate in the aquatic food chain and pose a threat to the health and reproductive success of people and wildlife that depend on locally caught fish as a source of dietary protein. Exposure to polychlorinated biphenyls (PCBs) and 1,1-bis(4-chlorophenyl)-2,2-dichloroethene (DDE) has been linked to higher rates of cancer, reproductive problems, and endocrine disorders. To investigate the effects of exposure to persistent contaminants of the Great Lakes Basin, the health departments of five Great Lakes states formed a health-assessment consortium. Between 1988 and 1994, the consortium collected demographic and fish consumption information from 2548 licensed charter boat captains, 182 anglers, and 1667 referents. Between 1994 and 1995, a subset of 619 participants in this study provided additional fish consumption information and donated blood samples that were analyzed for PCBs and DDE. Follow-up studies conducted between 2001 and 2005 re-assessed fish consumption rates and blood levels of PCBs and DDE in 293 of these individuals. While there was a trend for increasing overall fish consumption among most participant groups, sportfish and Great Lakes sportfish consumption decreased significantly in the captains over the study period. Serum DDE concentrations, which were highest in men in the captain and angler groups, declined in 90% of study participants. Mean DDE levels fell from 5.6 to 3.2 μg/L. Total PCB levels declined in 80% of participants with the mean concentration falling from 4.2 to 2.8 μg/L. Annual declines in serum DDE and PCB concentrations averaged 4.6% and 3.5%, respectively.     

ω-3脂肪酸对脓毒症病人治疗的影响

目的:探讨ω-3脂肪酸对脓毒症病人的免疫调节和抗炎作用。方法:将18例病人随机分为鱼油治疗组和常规治疗组。鱼油治疗组病人为常规治疗加鱼油,并于治疗前和治疗后第5天用流式细胞仪检测单核细胞HLA-DR表达率,同时检测炎症反应指标,包括C反应蛋白(CRP)、IL-6和肿瘤坏死因子α(TNF-α),观察病情严重程度(APACHEⅡ评分)和氧合指数(PaO2/FiO2)的变化。结果:相对于常规治疗组,鱼油治疗组病人血清CRP、IL-6和TNF-α均明显下降;氧合指数改善;单核细胞HLA-DR表达率、APACHEⅡ评分较常规治疗组无显著性差异。结论:应用ω-3脂肪酸可使脓毒症病人血清炎症介质表达减少,但对单核细胞HLA-DR的表达未见调节作用。