Do Soluble Cell Adhesion Molecules Play a Role in Endometriosis?

PROBLEM: Endometriosis is a chronic inflammatory disease associated with diverse immunologic disturbances. Cell adhesion molecules are essential for the development of immune and inflammatory reactions. This study was conducted to investigate whether or not serum and peritoneal levels of soluble cell adhesion molecules are altered in women with endometriosis. METHOD OF STUDY: The study group comprised five women with moderate-to-severe endometriosis. Eight healthy women with a normal diagnostic laparoscopy served as controls. Serum and peritoneal fluid samples from both groups were analyzed for the soluble isoform of intercellular cell adhesion molecule-1 (sICAM-1). vascular cell adhesion molecule-1 (sVCAM-1), endothelial selectin (sES), and platelet selectin (sPS). RESULTS: Serum levels of sICAM-1 were significantly increased in women with endometriosis (median levels: 410.4 ng/mL; range: 233.9 ng/mL 598.4 ng/mL vs. 235.7 ng/mL; range: 187.4 ng/mL -323.7 ng/mL; P = 0.02). Although the levels of sVCAM-1, sES, and sPS in both samples were higher in the study group, the differences did not reach significance. CONCLUSIONS: Our results suggest a role of ICAM-1 in the pathophysiology of endometriosis. However. the role of other investigated cell adhesion molecules should be confirmed by further studies.     

Do Regulatory T Cells Play a Role in the Control of Homeostatic Proliferation?

The control of peripheral lymphocyte numbers is a fundamental aspect of the immune system. Regulatory T cells are involved in the suppression of autoimmune, antitumor, allergic, and other inflammatory responses, as well as in facilitating graft acceptance. In this paper, we discuss whether the control of homeostatic proliferation is another facet of the immune system that is controlled by regulatory T cells. A review of the published data connecting regulatory T cells with the control of homeostatic proliferation indicates that several key questions remain open. One of these relates to the stage at which regulatory T cells could play a role (i.e., T-cell proliferation vs. survival).     

MicroRNAs Are Aberrantly Expressed in Hypertrophic Heart: Do They Play a Role in Cardiac Hypertrophy?

MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate gene expression. Although miRNAs are highly expressed in the heart, their roles in heart diseases are currently unclear. Using microarray analysis designed to detect the majority of mammalian miRNAs identified thus far, we demonstrated that miRNAs are aberrantly expressed in hypertrophic mouse hearts. The time course of the aberrant miRNA expression was further identified in mouse hearts at 7, 14, and 21 days after aortic banding. Nineteen of the most significantly dysregulated miRNAs were further confirmed by Northern blot and/or real-time polymerase chain reaction, in which miR-21 was striking because of its more than fourfold increase when compared with the sham surgical group. Similar aberrant expression of the most up-regulated miRNA, miR-21, was also found in cultured neonatal hypertrophic cardiomyocytes stimulated by angiotensin II or phenylephrine. Modulating miR-21 expression via antisense-mediated depletion (knockdown) had a significant negative effect on cardiomyocyte hypertrophy. The results suggest that miRNAs are involved in cardiac hypertrophy formation. miRNAs might be a new therapeutic target for cardiovascular diseases involving cardiac hypertrophy such as hypertension, ischemic heart disease, valvular diseases, and endocrine disorders.     

Do fish thrombocytes play an immunological role? Their cytoenzymatic profiles and function during an accidental piscine candidiasis in aquarium

Fish (F) thrombocytes (THRs) from healthy trouts were studied in terms of cytoenzyme expression. FTHRs were positive to acid periodic of shiff (PAS) and acid phosphatase (ac. phos.) without tartaric acid (-TA) stainings, as well to alkaline phosphatase. However, when compared with autologous macrophages (M psi's), they were negative to naphthol cloroacetate esterase (AS-D), alpha-naphthyl acetate esterase (Anae), peroxidase (perox) and control ac. phos. with tartaric acid (+TA) stainings, thus indicating a lack of typical lysosomial enzymes. This evidence supports the notion that FTHRs are not true digesting cells. Quite interestingly, trouts and human M psi's were positive for PAS, AS-D, Anae, and perox stainings, thus confirming that cellular cytochemistries are maintained across evolution as their phagocytic functions. Additionally, blood films from trouts, accidentally infected with Candida albicans in aquarium, were morphologically analyzed. Actually, FTHRs interact with erythrocytes, potentiating the formation of rosettes around a central Mpsi. Polymorph nuclear cells and lymphocytes are present in these cellular aggregates, thus suggesting that FTHRs may represent a link between innate and adaptive immunity.     

MicroRNA: Could It Play a Role in Bovine Endometritis?

Inflammation - Endometritis in dairy cows is a major economic problem worldwide; without advances in lifestyle management and drug treatment, it causes high morbidity and death. Micro ribonucleic...     

Success in Weight Management Among Patients with Type 2 Diabetes: Do Perceived Autonomy Support,Autonomous Motivation,and Self-Care Competence Play a Role?

Based on self-determination theory (SDT), this study investigated whether the three central SDT variables—perceived autonomy support (from a physician), autonomous motivation and self-care competence—were associated with success in weight management (SWM) among primary care patients with type 2 diabetes when the effect of other important life-context factors was controlled for. Patients participated in a mail survey in 2011. Those who had tried to change their health behavior during the past two years in order to lose weight, either with or without success (n = 1433, mean age 63 years, 50% men), were included in this study. The successors were more autonomously motivated and energetic than the non-successors. Moreover, male gender, younger age, taking oral medication only, and receiving less social support in diabetes care predicted better success. Autonomous motivation predicted SWM; self-care competence also played a role by partly mediating the effect of autonomous motivation on SWM. These results support the idea of SDT that internalizing the value of weight management and its health benefits is necessary for long-term maintenance of health behavior change. Perceived autonomy support was not directly associated with SWM. However, physicians can promote patients' weight management by supporting their autonomous motivation and self-care competence.     

Does Thrombin Play a Role in the Pathogenesis of Brain Damage After Periventricular Hemorrhage?

Neonatal periventricular hemorrhage (PVH) is a devastating complication of prematurity in the human infant. Based upon observations made primarily in adult rodents and the fact that the immature brain uses proteolytic systems for cell migration and growth, we hypothesized that thrombin and plasmin enzyme activities contribute to the brain damage after PVH. The viability of mixed brain cells derived from newborn rat periventricular region was suppressed by whole blood and thrombin, but not plasmin. Following injection of autologous blood into the periventricular region of newborn rat brain, proteolytic activity was detected in a halo around the hematoma using membrane overlays impregnated with thrombin and plasmin fluorogenic substrates. Two-day old rats received periventricular injection of blood, thrombin, and plasminogen. After 2 days, thrombin and blood were associated with significantly greater damage than saline or plasminogen. Two-day old mice received intracerebral injections of blood in combination with saline or the proteolytic inhibitors hirudin, alpha2macroglobulin, or plasminogen activator inhibitor-1. After 2 days, hirudin significantly reduced brain cell death and inflammation. Two-day-old mice then received low and high doses of hirudin mixed with blood after which behavioral testing was conducted repeatedly. At 10 weeks there was no statistically significant evidence for behavioral or structural brain protection. These results indicate that thrombin likely plays a role in neonatal periventricular brain damage following PVH. However, additional factors are likely important in the recovery from this result.     

Can the First Addition of Alkyl Radicals Play a Role in the Fate of NMP?

Values of k_d for the C? ON bond homolysis were measured for alkoxyamines based on imidazoline and imidazole nitroxides. They were analyzed in terms of polar/stabilization, steric, and entropic effects. k_d decreased with increasing electron‐withdrawing capacities of the groups attached to the nitroxide, but increasing with both the bulkiness of the group attached to the nitroxide and the presence of substituents on the ring. With three alkoxyamines, it was shown that the fate of the NMP of styrene depended on the type of initiating alkyl radical: successful for initiating 1‐phenylethyl radicals and unsuccessful for initiating p‐nitrophenyloxycarbonyl‐2‐prop‐2‐yl radicals.

     

Induction of TLR Tolerance in Human Macrophages by Adiponectin: Does LPS Play a Role?

Obesity is regarded as a pro-inflammatory state. It is associated with low circulating levels of the adipokine, adiponectin, which is considered to be an anti-inflammatory. However, adiponectin knockout mice do not consistently demonstrate pro-inflammatory phenotypes, suggesting more complexity in the in vivo immunomodulatory effects of adiponectin than originally anticipated. Moreover, adiponectin exerts pro-inflammatory effects in some experimental systems. This contradiction has been resolved by hypothesizing that adiponectin induces tolerance to inflammatory stimuli, notably Toll-like receptor (TLR) ligands. We noticed that this effect resembled lipopolysaccharide (LPS) tolerance and therefore tested adiponectin from a variety of sources for LPS contamination. All adiponectin tested carried low levels of LPS in the range of 1–30 pg/μg of adiponectin, sufficient to produce final LPS concentrations in the pg/ml range under experimental conditions. We found that induction of tolerance to TLR ligands by adiponectin in human monocyte-derived macrophages could be reproduced by such LPS concentrations. Moreover, the LPS antagonist, polymixin B, substantially inhibited induction of tolerance by adiponectin. Furthermore, polymixin B and a naturally occurring antagonist LPS were able to partially attenuate induction of tumour necrosis factor-α and interleukin-6 in human monocyte-derived macrophages by adiponectin. Polymixin B also inhibited nuclear factor-κB and mitogen-activated protein kinase signalling elicited by adiponectin. We therefore propose that some of adiponectin's immunomodulatory effects, in particular, its TLR-tolerising actions in human monocyte-derived macrophages, may be confounded by induction of tolerance by contaminating LPS.     

Is there an Inflammation Role for MYD88 in Rheumatoid Arthritis?

Inflammation - Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease with strong genetic influence, especially upon immune response components. Several cytokines from the toll-like...     

Do ATP and NO interact in the CNS?

Enzymatically derived NO and extracellular ATP are receiving greater attention due to their role as messengers in the CNS during different physiological and pathological processes. Ionotropic (P2XR) and metabotropic (P2YR) purinergic receptors mediate ATP effects and are present throughout the body. Particularly P2XR are crucial for brain plasticity mechanisms, and are involved in the pathogenesis of different CNS illnesses. NO does not have a specific receptor and its actions are directly dependent on the production on demand by different nitric oxide synthase isoforms. NO synthesizing enzymes are present virtually in all tissues, and NO influences multifarious physiological and pathological functions. Interestingly, various are the tissue and organs modulated by both ATP and NO, such as the immune, brain and vascular systems. Moreover, direct interactions between purinergic and nitrergic mechanisms outside the CNS are well documented, with several studies also indicating that ATP and NO do participate to the same CNS functions. In the past few years, further experimental evidence supported the physiological and pathological relevance of ATP and NO direct interactions in the CNS. The aim of the present review is to provide an account of the available information on the interplay between purinergic and nitrergic systems, focussing on the CNS. The already established relevance of ATP and NO in different pathological processes would predict that the knowledge of ATP/NO cross-talk mechanisms would support pharmacological approaches toward the development of novel ATP/NO combined pharmacological agents.     

Do we need dissection in an integrated problem-based learning medical course? Perceptions of first- and second-year students

BACKGROUND: The introduction of a problem-based learning (PBL) curriculum at the School of Medicine of the University of Melbourne has necessitated a reduction in the number of lectures and limited the use of dissection in teaching anatomy. In the new curriculum, students learn the anatomy of different body systems using PBL tutorials, practical classes, pre-dissected specimens, computer-aided learning multimedia and a few dissection classes. The aims of this study are: (1) to assess the views of first- and second-year medical students on the importance of dissection in learning about the anatomy, (2) to assess if students' views have been affected by demographic variables such as gender, academic background and being a local or an international student, and (3) to assess which educational tools helped them most in learning the anatomy and whether dissection sessions have helped them in better understanding anatomy. METHODS: First- and second-year students enrolled in the medical course participated in this study. Students were asked to fill out a 5-point Likert scale questionnaire. Data was analysed using Mann-Whitney's U test, Wilcoxon's signed-ranks or the calculation of the Chi-square value. RESULTS: The response rates were 89% for both first- and second-year students. Compared to second-year students, first-year students perceived dissection to be important for deep understanding of anatomy (P < 0.001), making learning interesting (P < 0.001) and introducing them to emergency procedures (P < 0.001). Further, they preferred dissection over any other approach (P < 0.001). First-year students ranked dissection (44%), textbooks (23%), computer-aided learning (CAL), multimedia (10%), self-directed learning (6%) and lectures (5%) as the most valuable resources for learning anatomy, whereas second-year students found textbooks (38%), dissection (18%), pre-dissected specimens (11%), self-directed learning (9%), lectures (7%) and CAL programs (7%) as most useful. Neither of the groups showed a significant preference for pre-dissected specimens, CAL multimedia or lectures over dissection. CONCLUSIONS: Both first- and second-year students, regardless of their gender, academic background, or citizenship felt that the time devoted to dissection classes were not adequate. Students agreed that dissection deepened their understanding of anatomical structures, provided them with a three-dimensional perspective of structures and helped them recall what they learnt. Although their perception about the importance of dissection changed as they progressed in the course, good anatomy textbooks were perceived as an excellent resource for learning anatomy. Interestingly, innovations used in teaching anatomy, such as interactive multimedia resources, have not replaced students' perceptions about the importance of dissection.     

Why Do Boys Engage in More Risk Taking Than Girls? The Role of Attributions, Beliefs, and Risk Appraisals

Objective: Assessed for age and sex differences in school-agechildren's reporting of injury-risk behaviors, ratings of injury-riskin various play situations, attributions for injuries (self,other, bad luck), and beliefs about their vulnerability to injuryin comparison to their peers (more, less, comparable vulnerability). Methods: We used a structured interview and drawings that depictedchildren showing wary or confident facial expressions when engagedin injury-risk play activities. Results: Children's reported risk taking could be predictedfrom their risk appraisals, beliefs about the likelihood ofinjury, and attributions of injuries to bad luck, and thesefactors resulted in 80% correct assignment of cases by sex ina discriminant analysis. The wary affect display resulted inhigher injury-risk ratings than the confident display, withthis effect being greater for girls than boys. Conclusions: Cognitive-based factors differentiate boys fromgirls and contribute to sex differences in children's injury-riskbehaviors.     

Do chemokines spark autoimmunity in juvenile and adult rheumatic disease?

The recent increase in knowledge on chemokines contributes substantially to the understanding of autoimmune inflammatory diseases, as cell migration is an essential prerequisite for the local immune reaction. The purpose of this review is to summarize the essential functions of chemokines in immune activation and to examine their role(s) in the initiation and perpetuation of autoimmunity in juvenile idiopathic arthritis and adult rheumatic disease. The possible relevance of chemokines as therapeutical targets will be discussed.     

Do Deductive and Probabilistic Reasoning Abilities Decline in Older Adults?

This present study investigated whether older adults' ability to accurately discriminate between deductive and probabilistic reasoning tasks declines with age, and whether this ability correlates with cognitive ability as measured by the Montreal Cognitive Assessment (MoCA) test. Seventy‐eight adults (65–92 years) were tested for their abilities to carry out deductive and probabilistic reasoning. Pearson correlations were conducted to determine the relationships among age, MoCA, deductive reasoning, probabilistic reasoning, and overall discrimination ability. Separate single‐factor analyses of variance were used to determine differences across age groups (65–74, 75–84, 85–94) on the MoCA, deductive and probabilistic reasoning, and overall discrimination ability. Ability to discriminate between the two tasks did not decline with age, nor did they correlate with scores of cognitive ability as measured by the MoCA. Furthermore, those with MoCA scores showing mild cognitive impairment appeared to retain all of these abilities. This leads to the conclusion that reasoning abilities may be retained while general cognitive skills decline. This in turn supports the notion that reasoning, both deductive and probabilistic, may be more domain specific than they are often considered to be.