Parahippocampal corpora amylacea and neuronal lipofuscin in human aging

The aim of this research was to quantify the number of corpora amylacea and lipofuscin-bearing neurons in the parahippocampal region of the brain. Right parahippocampal gyrus specimens of 30 cadavers were used as material for histological and morphometric analyses. A combined Alcian Blue and Periodic Acid-Schiff technique was used for identification and quantification of corpora amylacea and lipofuscin-bearing neurons. Immunohistochemistry was performed using S100 polyclonal, neuron-specific enolase and glial fibrillary acidic protein monoclonal antibodies for differentiation of corpora amylacea and other spherical inclusions of the aging brain. Cluster analysis of obtained data showed the presence of three age groups (median age: I = 41.5, II = 68, III = 71.5). The second group was characterized by a significantly higher numerical density of subcortical corpora amylacea and number of lipofuscin-bearing neurons than other two groups. Values of the latter cited parameters in the third group were insignificantly higher than the first younger group. Linear regression showed that number of parahippocampal lipofuscin-bearing neurons significantly predicts numerical density of subcortical corpora amylacea. The above results suggest that more numerous parahippocampal region corpora amylacea and lipofuscin-bearing neurons in some older cases might represent signs of its’ neurons quantitatively-altered metabolism.     

Comparison of two nutritional assessment methods in gastroenterology patients

AIM:To investigate and compare efficacy and differences in the nutritional status evaluation of gastroenterology patients by application of two methods:subjective global assessment(SGA) and nutritional risk index(NRI).METHODS:The investigation was performed on 299 hospitalized patients,aged 18-84 years(average life span 55.57 ± 12.84),with different gastrointe-stinal pathology,admitted to the Department of Gastroenterohepatology,Clinical and Hospital Center “Bezanijska Kosa“ during a period of 180 d.All the...     

An exploratory study of systemic administration of the toll-like receptor-7 agonist 852A in patients with refractory metastatic melanoma.

PURPOSE: A topical Toll-like receptor 7 (TLR7) agonist induces regression of cutaneous melanocytic neoplasms. We explored antitumor activity of a systemically administered TLR7 agonist, 852A, in patients with metastatic melanoma. EXPERIMENTAL DESIGN: We undertook a phase II, multicenter, open-label study in patients with chemotherapy-refractory metastatic melanoma. Patients received i.v. 852A, starting at 0.6 mg/m(2) and increasing to 0.9 mg/m(2) based on tolerance, thrice per week for 12 weeks. Clinical response was determined by Response Evaluation Criteria in Solid Tumors. Immune effects of 852A were monitored by measuring serum type I IFN and IP-10 together with assessment of immune cell markers in peripheral blood. RESULTS: Twenty-one patients were enrolled. Thirteen patients completed the initial 12-week treatment cycle, with two discontinuing for adverse events considered to be possibly related to study drug. Four (19%) patients had disease stabilization for >100 days. One patient had a partial remission after two treatment cycles, but progressed during the third. Dose-limiting toxicity was observed in two patients. Serum type I IFN and IP-10 increased in most patients on 852A administration. Serum type I IFN increases were greater after dosing with 852A 0.9 mg/m(2) than after 0.6 mg/m(2) (P = 0.009). The maximal increase in IP-10 compared with baseline correlated with the maximal increase in type I IFN (P = 0.003). In the eight patients with immune cell marker data, CD86 expression on monocytes increased significantly post-first dose (P = 0.007). CONCLUSION: Intravenous 852A was well tolerated and induced systemic immune activation that eventually resulted in prolonged disease stabilization in some patients with stage IV metastatic melanoma who had failed chemotherapy.     

Correlation between age-related changes in open field behavior and plaque forming cell response in DA female rats

We investigated the relationship between immunological and behavioral changes during ageing in Dark Agouti female rats. Results showed that ageing was associated with decreased exploratory behavior and increased emotionality (open field test) and decreased pain perception (writhing assay), but not with altered depression-like behavior (forced swim test). The observed behavioral changes were paralleled with decreased innate immunity in middle-aged and old rats, as revealed by reduced peroxide production of peritoneal macrophages; and decreased specific immunity, measured by the plaque-forming cell response, in old rats in comparison with young rats. Correlation analyses between behavioral and immune parameters demonstrated a significant correlation between the lines crossed in the open field test and the plaque-forming cell response. Taken together, the demonstrated age-dependent association between exploratory behavior and specific immune response suggests a senescent decline of a common neuroimmune regulatory mechanism.     

The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations

Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric syndrome, affecting human infants and adolescents. Two main behavioural features are reported: (1). impaired attention and (2). an impulsive-hyperactive behavioural trait. The latter has been studied in a series of experiments, using the spontaneously hypertensive-rat (SHR) strain (which is regarded as a validated animal model for ADHD) in operant tasks. Food-restricted SHRs and their Wistar-Kyoto (WKY) controls were tested during adolescence (i.e. post-natal days 30-45), in operant chambers provided with two nose-poking holes. Nose-poking in one hole (H1) resulted in the immediate delivery of a small amount of food, whereas nose-poking in the other hole (H5) delivered a larger amount of food after a delay, which was increased progressively each day (0-100 s). As expected, all animals showed a shift in preference from the large (H5) to the immediate (H1) reinforcer as the delay length increased. Impulsivity can be measured by the steepness of this preference-delay curve. The two strains differed in home-cage circadian activity, SHRs being more active than WKYs at several time-points. During the test for impulsivity, inter-individual differences were completely absent in the WKY strain, whereas a huge inter-individual variability was evident for SHRs. On the basis of the median value of average hole-preference, we found an 'impulsive' SHR subgroup, with a very quick shift towards the H1 hole, and a flat-slope ('non-impulsive') SHR subgroup, with little or no shift. The impulsive subpopulation also presented reduced noradrenaline levels in both cingulated and medial-frontal cortex, as well as reduced serotonin turnover in the latter. Also, cannabinoid CB1 receptor density resulted significantly lower in the prefrontal cortex of impulsive SHRs, when compared to both the non-impulsive subgroup and control WKYs. Interestingly, acute administration of a cannabinoid agonist (WIN 55,212, 2 mg/kg s.c.) normalized the impulsive behavioural profile, without any effect on WKY rats. Thus, two distinct subpopulations, differing for impulsive behaviour and specific neurochemical parameters, were evidenced within adolescent SHRs. These results support the notion that a reduced cortical density of cannabinoid CB1 receptors is associated with enhanced impulsivity. This behavioural trait can be positively modulated by administration of a cannabinoid agonist. Present results confirm and extend previous literature, indicating that adolescent SHRs represent a suitable animal model for the preclinical investigation of the early-onset ADHD syndrome.     

Behavior of sunbed users in Switzerland

OBJECTIVES: A constant rise in the number of skin cancer cases has been observed during the last few years. An important reason for this trend is that exposure of the population to UV radiation is higher. Although natural UV radiation is the major source, exposure due to use of sunbeds must be considered from the point of view of prevention. METHODS: 151 sunbed users in Bern and Basel were questioned on their reasons for visiting a solarium, their behaviour when using a sunbed and their awareness of risks resulting from UV radiation. RESULTS: It was shown that young women are the most frequent sunbed users. Also, sunbeds are often used regularly, not only for cosmetic reasons but also from a desire for relaxing and well-being in the warmth and light. Although most of the persons questioned were aware of certain health risks resulting from UV radiation, this knowledge hardly influenced their behaviour. Thus, more than half the people questioned use sunbeds longer and more often than advised by international recommendations. CONCLUSIONS: In view of a continuing increase in the number of skin cancer cases the improvement of preventive strategies for sunbed users is of major importance. Another urgent requirement is informing the public and increasing the general awareness of possible adverse health effects caused by UV radiation.     

Aminopeptidase inhibitors bestatin and actinonin inhibit cell proliferation of myeloma cells predominantly by intracellular interactions

Dimethylarsinic acid (DMA), a major metabolite of inorganic arsenics, and arsenic exposure is associated with tumor development in a wide variety of human tissues. In the present study, we examined whether DMA has tumor-promoting activity on rat lung carcinogenesis initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Male, 8-week-old, F344 rats were treated with DHPN at a concentration of 0.1% in drinking water for 1 week, and starting 1 week thereafter, DMA was administered at concentrations of 0, 100, 200 or 400 ppm in the drinking water for 30 weeks. Induction of epithelial lesions, classified as alveolar epithelial hyperplasia, adenoma, and adenocarcinoma was evident in the lungs of DHPN-initiated animals, but no significant differences were found between DMA-treated groups and control groups. Furthermore, no significant differences in 5-bromo-2'-deoxyuridine labeling indices, as a marker of cell proliferation were observed among the groups. An additional group treated with DMA at concentrations of 200 ppm alone, without prior DHPN initiation was found to develop no epithelial lesions in the lung. There was no significant gain in 8-hydroxydeoxyguanosine formation, as a marker of oxidative stress, in the lungs of rats treated with DMA in their drinking water. In conclusion, oral-administered DMA does not exert promoting effects on rat lung carcinogenesis initiated with DHPN.     

Effect of neuropeptide Y on inflammatory paw edema in the rat: involvement of peripheral NPY Y1 and Y5 receptors and interaction with dipeptidyl-peptidase IV (CD26)

Several lines of evidence suggest that neuropeptide Y (NPY) may exert regulatory effects in local inflammatory responses. Here, we show that intraplantarly (i.pl.) applied NPY, peptide YY (PYY), and an NPY Y5 receptor-selective agonist dose-dependently potentiate concanavalin A (Con A)-induced paw edema in the rat. The NPY Y1 receptor antagonist BIBO 3304 abolishes the pro-inflammatory action of both NPY and PYY while the dipeptidyl-peptidase IV (CD26) inhibitor Ile-thiazolidide exerted synergistic and potentiating effects in vivo. Taken together, the present data reveal an NPY Y1/Y5 receptor interplay and an involvement of CD26 in the NPY-induced potentiation of paw edema in the rat.     

Rabies treatment of health care staff

This article deals with post-exposure treatment of contacts of human cases of rabies. Experience suggests that rabies is hardly ever transmitted from person to person if at all. With the modern generation of vaccines against rabies, the use of post-exposure treatment is more widespread. A lot of contacts of patients with rabies in developed countries are treated, most of them being health care workers. This treatment is however not practised so often in developing countries where the supply of highly protective vaccines with a few side effects is low. According to reports good hygienic practice in nursing these patients is well established.