Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end‐stage renal disease (ESRD) patients treated by hemodialysis (HD). Although traditional risk factors are common in dialysis patients, they may not alone be sufficient to account for the unacceptable high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor that is commonly observed in HD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The cause(s) of inflammation in HD patients is multifactorial and includes both dialysis‐related (such as graft and fistula infections, bioincompatibility, impure dialysate, and back‐filtration) and dialysis‐unrelated factors. Although inflammation may reflect underlying CVD, an acute‐phase reaction may also be a direct cause of vascular injury. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there is not yet any recognized, or even proposed, targeted treatment for ESRD patients with chronic inflammation; it would be of considerable interest to study the long‐term effect of various anti‐inflammatory treatment strategies on nutritional and cardiovascular status as well as outcome in these patients.     

Clinical adolescent psychology: What it is, and what it needs to be.

This commentary on the special section on clinical adolescent psychology (G. Holmbeck & P. Kendall, 2002) reviews and critiques the conceptual and empirical articles that this compilation comprises. As articulated in the conceptual contributions to this collection, two fundamental principles should guide research on the etiology, prevention, and treatment of psychological disorder and dysfunction during adolescence: First, drawing on the field of developmental psychopathology, the study of clinical adolescent psychology should focus on the trajectories of disorder that precede, characterize, and follow adolescence. Second, drawing on the literature on normative adolescent development, the study of clinical adolescent psychology must proceed with an explicit recognition of the unique biological, cognitive, psychosocial, and contextual features that define adolescence as a developmental period. Although the study of clinical adolescent psychology, as evidenced by this collection of articles, is appropriately grounded in the broader enterprise of developmental psychopathology, less progress has been made with respect to die integration of the study of clinical phenomena in adolescence with the study of normative adolescent development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reading difficulty--a psycho-educational analysis of a cognitive dysfunction.

Although much progress has been achieved in the field of education in the last half-century, it is still a fact that a great number of our children are not achieving their full learning potential, and we are facing an ever growing number of children with reading difficulties. According to a recent survey in a big urban centre in U.S.A., 28 per cent of all sixth-graders were found to read two or more grades below the expected grade level, which is the conventional definition of severe reading retardation. And yet this state of affairs seems paradoxical because reading is considered, and known to be, a very easy learning task. It is a psychologically and educationally known fact that from age 4-5 reading can be acquired at any age as proven by educational movements against illiteracy throughout the world. Although, in essence, reading is a purely educational problem-reading difficulty, its nature, its varieties of expression and its causality, extend far beyond the reaches and comprehension of an educational system. This is why education found itself suddenly embracing confusingly a multitude of professions, each one pulling in its own direction. In our opinion, the problem can be solved only if a sound functional interaction is established between education, psychology and medicine. This interaction was achieved in the Children's Service of Douglas Hospital, where teachers, psychologists and psychiatrists work together. The result of this cooperation is a different approach towards the understanding of reading difficulty and the remedial-corrective measures to be developed. We conceive of reading difficulty primarily as a symptom of a cognitive-dysfunction. Following this basic assumption we are developing a new "Thematic-sequential" reading-primer which will not only give the teacher an educationally conceived method, but also takes into consideration the nature of the reading difficulties on a background of impaired cognitive development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Structural identification of a new acetildenafil analogue from pre-mixed bulk powder intended as a dietary supplement

An analogue of acetildenafil was detected in an extract of pre-mixed bulk powder. To our knowledge, the powder was destined to be encapsulated and sold as a dietary supplement. The structure was identified by NMR, HR-ESI-MS, ESI-MSⁿ and FTIR analyses. Owing to the inclusion of a hydroxyl group in acetildenafil, the detected compound was called 'hydroxyacetildenafil'. With increasing use of dietary supplements marketed for penile erectile dysfunction, the detection of analogues of sexual performance enhancers is important and timely.     

Review of Sexuality and chronic illness: A comprehensive approach.

Reviews the book, Sexuality and chronic illness: A comprehensive approach by Leslie R. Schover and Soren Buus Jensen (see record 1988-98146-000) as well written and carefully organized. Part 1 covers an integrative model of sexuality assessment and treatment, Part 2 covers specific illnesses and sexuality, and Part 3 discusses training and ethical issues. The text is designed for clinicians addressing sexuality concerns of patients with chronic illness as well as health care professionals. The authors assume that readers will need basic information about sexuality and, therefore include reviews of theoretical approaches to sexuality and sexual dysfunction, the sexual response cycle, and intervention strategies used with people with sexual dysfunction. The medical information provided allows the non-physician to understand the physiological bases of sexual response and dysfunction, and the medical interventions described in the text is comprehensive and easy to understand. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Role of TRPM2 in Endothelial Function and Dysfunction

The transient receptor potential (TRP) melastatin-like subfamily member 2 (TRPM2) is a non-selective calcium-permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best-known mechanism of TRPM2 activation is related to the binding of ADP-ribose to the nudix-box sequence motif (NUDT9-H) in the C-terminal domain of the channel. In cells, the production of ADP-ribose is a result of increased oxidative stress. In the context of endothelial function, TRPM2-dependent calcium influx seems to be particularly interesting as it participates in the regulation of barrier function, cell death, cell migration, and angiogenesis. Any impairments of these functions may result in endothelial dysfunction observed in such conditions as atherosclerosis or hypertension. Thus, TRPM2 seems to be an attractive therapeutic target for the conditions connected with the increased production of reactive oxygen species. However, before the application of TRPM2 inhibitors will be possible, some issues need to be resolved. The main issues are the lack of specificity, poor membrane permeabilization, and low stability in in vivo conditions. The article aims to summarize the latest findings on a role of TRPM2 in endothelial cells. We also show some future perspectives for the application of TRPM2 inhibitors in cardiovascular system diseases.     

Lacticaseibacillus paracasei K71 Alleviates UVB-Induced Skin Barrier Dysfunction by Attenuating Inflammation via Increased IL-10 Production in Mice

Scope

Ultraviolet B (UVB) radiation causes skin barrier dysfunction, leading to decreased water-holding capacity, impaired epidermal barrier function, and increased skin thickness. This study investigates the protective effects of oral administration of Lacticaseibacillus paracasei K71 against skin barrier dysfunction in UVB-irradiated mice.

Methods and results

Mice are fed diets with or without K71 and irradiated with UVB three times a week for 12 weeks. Oral administration of K71 suppresses UVB-induced decrease in stratum corneum water content, mitigates the increase of transepidermal water loss, and decreases epidermal thickness of the dorsal skin. Treatment with K71 reverses the upregulation of inflammatory cytokines and the activation of nuclear factor-κB induced by UVB irradiation and upregulates the expression of anti-inflammatory IL-10 in the dorsal skin. Notable upregulation of IL-10 is observed in the spleens of K71-treated mice. K71 treatment enhances IL-10 production in J774.1 macrophages; however, this enhancement is diminished by inhibiting K71 phagocytosis and TLR3. Furthermore, transfection using K71 RNAs significantly increases IL-10 production.

Conclusion

These results indicate that K71 may alleviate UVB-induced skin barrier dysfunction by attenuating inflammation via increasing IL-10 production and that K71 RNAs may induce IL-10 production in macrophages. Therefore, K71 may be beneficial for preventing skin barrier dysfunction.     

Effects of hindgut acidosis on production,metabolism, and inflammatory biomarkers in previously immune-activated lactating dairy cows

Previous stressors and systemic inflammation may increase the intestine's susceptibility to hindgut acidosis (HGA). Therefore, our experimental objectives were to evaluate the effects of isolated HGA on metabolism, production, and inflammation in simultaneously immune-activated lactating cows. Twelve rumen-cannulated Holstein cows (118 ± 41 d in milk; 1.7 ± 0.8 parity) were enrolled in a study with 3 experimental periods (P). Baseline data were collected during P1 (5 d). On d 1 of P2 (2 d), all cows received an i.v. lipopolysaccharide (LPS) bolus (0.2 µg/kg of body weight; BW). During P3 (4 d), cows were randomly assigned to 1 of 2 abomasal infusion treatments: (1) control (LPS-CON; 6 L of H₂O/d; n = 6) or (2) starch infused (LPS-ST; 4 kg of corn starch + 6 L of H₂O/d; n = 6). Treatments were allocated into 4 equal doses (1.5 L of H₂O or 1 kg of starch and 1.5 L of H₂O, respectively) and administered at 0000, 0600, 1200, and 1800 h daily. Additionally, both treatments received i.v. LPS on d 1 and 3 of P3 (0.8 and 1.6 µg/kg of BW, respectively) to maintain an inflamed state. Effects of treatment, time, and their interaction were assessed. Repeated LPS administration initiated and maintained an immune-activated state, as indicated by increased circulating white blood cells (WBC), serum amyloid A (SAA), and LPS-binding protein (LBP) during P2 and P3 (29%, 3-fold, and 50% relative to P1, respectively) for both abomasal infusion treatments. Regardless of abomasal treatment, milk yield and dry matter intake were decreased throughout P2 and P3 but with lesser severity following each LPS challenge (54, 44, and 37%, and 49, 42, and 40% relative to baseline on d 1 of P2, d 1 and d 3 of P3, respectively). As expected, starch infusions markedly decreased fecal pH (5.56 at nadir vs. 6.57 during P1) and increased P3 fecal starch relative to LPS-CON (23.7 vs. 2.4% of dry matter). Neither LPS nor starch infusions altered circulating glucose, insulin, nonesterified fatty acids, or β-hydroxybutyrate, although LPS-ST cows had decreased blood urea nitrogen throughout P3 (16% relative to LPS-CON). Despite the striking reduction in fecal pH, HGA had no additional effect on circulating WBC, SAA, or LBP. Thus, in previously immune-activated dairy cows, HGA did not augment the inflammatory state, as indicated by a lack of perturbations in production, metabolism, and inflammatory biomarkers.