Effect of HFA-flunisolide on peripheral lung inflammation in asthma

BACKGROUND: New hydrofluoroalkane (HFA) formulations of glucocorticoids have been shown to effectively control asthma. HFA glucocorticoids are deposited across all sizes of airways, including the small ones. However, it is not clear whether they can suppress peripheral airway inflammation. OBJECTIVE: We sought to determine whether HFA-flunisolide could suppress peripheral inflammation in asthma. METHODS: Twelve patients with mild to moderate asthma received HFA-flunisolide for 6 weeks. Transbronchial and endobronchial biopsy specimens were obtained before and after treatment, and spirometry was performed. Changes in inflammatory cells (eosinophils, neutrophils, lymphocytes, macrophages, basophils) and IL-5 and eotaxin were measured by using immunocytochemistry and in situ hybridization. RESULTS: Lung function significantly improved after treatment (P <.05). HFA-flunisolide significantly reduced eosinophils, IL-5, and eotaxin in both peripheral and central airways (P <.01). Neutrophils significantly increased after treatment in peripheral and central airways (P <.05). The numbers of lymphocytes remained unchanged. CONCLUSIONS: These results show that HFA-flunisolide effectively suppressed eosinophilic inflammation in peripheral and central airways. These changes were accompanied by improvement in lung function.     

Chitinases and chitinase-like proteins in T(H)2 inflammation and asthma

Chitin is the second most abundant biopolymer in nature, where it protects crustaceans, parasites, fungi, and other pathogens from the adverse effects of their environments, hosts, or both. Because chitin does not exist in mammals, it had been assumed that the chitinases that degrade it are also restricted to lower life forms. However, chitinases and chitinase-like proteins have recently been noted in mice and human subjects. The prototypic chitinase, acidic mammalian chitinase, was also noted to be induced during T(H)2 inflammation through an IL-13-dependent mechanism. It was also shown to play an important role in the pathogenesis of T(H)2 inflammation and IL-13 effector pathway activation and demonstrated to be expressed in an exaggerated fashion in human asthmatic tissues. The finding that chitinases contribute to host anti-parasite responses and asthmatic T(H)2 inflammation support the concept that asthma might be a parasite-independent anti-parasite response.     

Evidence for increased expression of eotaxin and monocyte chemotactic protein-4 in atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with tissue eosinophilia and the activation of T lymphocytes. The novel eosinophil chemoattractants, eotaxin and monocyte chemotactic protein (MCP)-4, are up-regulated at sites of allergic inflammation, yet their contribution to the pathophysiologic mechanisms of AD remains to be determined. OBJECTIVE: We sought to investigate the expression of eotaxin and MCP-4 in acute and chronic lesions from patients with AD and to determine their relationship to the numbers of resident inflammatory cells. METHODS: With use of in situ hybridization, the expression of eotaxin and MCP-4 messenger RNA (mRNA) in skin biopsy specimens from patients with acute and chronic AD skin lesions was compared with that of uninvolved skin from these patients and skin from healthy volunteers. RESULTS: There was a constitutive expression of eotaxin and MCP-4 mRNA in skin biopsy specimens from healthy subjects. Positive signal for chemokine mRNA was observed both within the epidermis and inflammatory cells (macrophages, eosinophils, and T cells) of the subepidermis in AD skin lesions. Within the subepithelium acute and chronic skin lesions exhibited a significant increase in the numbers of eotaxin and MCP-4 mRNA-positive cells compared with uninvolved skin (P <.01), whereas the numbers of eotaxin and MCP-4 mRNA-positive cells were significantly higher in chronic AD compared with acute AD skin lesions (P <.005, P <.001, respectively). Correlations were observed between the expression of eotaxin and MCP-4 mRNA and the presence of eosinophils and macrophages, respectively, in AD lesions (r(2) = 0.84, r(2) = 0.94). CONCLUSION: There is an increased expression of eotaxin and MCP-4 in acute and chronic lesions, suggesting that these chemotactic factors play a major role in the pathophysiologic mechanisms of AD.     

Seroprevalence of HBsAg, anti-HCV, and anti-HIV among haemophiliac patients in Shiraz, Iran

A study was performed during 1999-2000 on multi-transfused patients with haemophilia who are registered by the Shiraz Haemophilia Society. HBsAg, anti-HCV, and anti-HIV were checked using a second-generation enzyme-linked immunosorbent assay (ELISA). Positive tests for anti-HCV and anti-HIV were confirmed by a western blot test. Healthy blood donors were used for the control group. HBsAg, anti-HCV, and anti-HIV were positive in two (0.71%, 95% CI = 0.12-2.33), 44 (15.65%, 95% CI = 11.76-20.26), and one (0.36%, 95% CI = 0.02-1.74) of the patients, respectively. Positive sera for HBsAg, anti-HCV, and anti-HIV were found in 85 (1.07%), 47 (0.59%), and 27 (0.34%) of the control group, respectively. The rate of anti-HCV was significantly higher in the patients than in the control group (p < 0.0001). The rate of positive anti-HCV was significantly higher than that of positive HBsAg in the patients (p < 0.0001). The reverse was correct for the control group (p = 0.0008). It is concluded that HCV is the current major problem in multi-transfused haemophiliac patients and more careful pre-transfusion screening of blood for anti-HCV must be introduced in all blood banks.     

Genetic and biochemical characterization of Malassezia pachydermatis with particular attention to pigment-producing subgroups.

The aim of the study was the characterization of Malassezia pachydermatis and its pigment-producing subgroup using biochemical tests and RAPD. It was of interest to determine whether particular RAPD patterns could be used to indicate pigment production, as well as a close genetic relatedness to Malassezia furfur. Therefore, 210 strains of M. pachydermatis were examined for morphology, catalase and ss-glucosidase activity, lipid and carbohydrate assimilation and the tryptophan-dependent synthesis of pigments. Of these, 114 strains were subjected to RAPD analyses. A multivariate logistic regression model was applied to classify M. pachydermatis isolates regarding their pigment production by using genetic and biological parameters. Biological and RAPD findings showed a high biological and genetic diversity within the species M. pachydermatis and within pigment producers. RAPD analysis revealed 28 genotypes within 114 strains tested. Pigment producing strains could not be assigned to a common RAPD profile, but a genetic relatedness of pigment-producing M. pachydermatis with M. furfur can be assumed. A particular RAPD pattern allowed statistically significant probability of pigment production (P<0.001) and might be used as a tool to rapidly detect pigment producing M. pachydermatis, e.g. in Malassezia-associated pityriasis versicolor. The reported method is useful for identification of pigment producing M. pachydermatis isolates and has advantages over established tests.     

Phenotype-genotype characterization of 10 families with severe a subunit factor XIII deficiency

Factor XIII (FXIII) deficiency is a very rare severe autosomal bleeding disorder with a frequency of 1:2,000,000 in the general population and only a few patients have been genetically characterized so far. We report a phenotype-genotype characterization of 10 unrelated Iranian patients. Two FXIII (transglutaminase) activity assays showed no FXIII activity, except a conserved residual activity in patients receiving prophylactic substitution treatment. FXIII antigen concentrations measured by two immunoassays were comparable. Genotype characterization identified four novel mutations (2 missense and 2 small deletions) and two previously reported missense mutations in the FXIII A subunit gene (F13A). Molecular modeling was carried out to reveal the structural consequences of the missense mutations, that caused the replacement of an arginine residue involved in the formation of structurally important extensive hydrogen-bonded network. The replacements [c.320G>A (p.Arg77His) in the beta-sandwich, c.868C>T (p.Arg260Cys), c.869G>A (p.Arg260His) and c.1236G>T (p.Arg382Ser) in the core domain] resulted in the loss or impairment of such H-bonded network. Energy decomposition analysis demonstrated that this situation leads to the instability and perhaps to the incorrect folding of the A subunit, that would explain the development of severe FXIII deficiency.     

The human lumbar anterior epidural space: morphological comparison in adult and fetal specimens

To increase our understanding of the clinical anatomy of the epidural space, the human lumbar anterior epidural space was studied morphologically and developmentally. Histological transverse sections of human lumbar spines were taken at the level of the intervertebral disc and the vertebral body in adult specimens and in fetuses aged 13, 15, 21, 32 and 39 weeks (menstrual age). At 13 weeks, connective tissue filled the epidural space. The dura mater was attached anteriorly to the posterior longitudinal ligament (PLL). The PLL was attached to the vertebral body beside the midline, whereas it adhered to the posterior edge of intervertebral disc. The anterior internal vertebral venous plexus was located anterolaterally and anteromedially. The vertebral canal was lined with connective tissue that differentiated in a periosteum in contact with the ossification centers. At 15 weeks, the PLL was composed of deep and superficial layers. At 21 weeks, the attachment between the dura mater and PLL was ligament-like at the level of the vertebral body. At 32 weeks, the dura mater was adherent to the superficial layer of PLL. At 39 weeks, groups of adipocytes were identified, and the dura mater was attached to the PLL by some ligaments. There were many more similarities between the adult and the 39-week fetus. In conclusion, some differences in the anatomy of the epidural space exist at each fetal stage studied. The structures of the epidural space are already formed in the fetus of 13 weeks, but they differentiate progressively within the connective tissue.     

Daily running promotes spatial learning and memory in rats.

Previous studies on exercise have shown that physical activity improves learning and memory. Present study was performed to determine the effects of acute, chronic and continuous exercise with different periods on spatial learning and memory recorded as the latency and length of swim path in the Morris water maze testing in subsequent 8 days. Four rat groups were included as follows: (1) group C, controls which did not exercise; (2) group A, 30 days treadmill running before and 8 days during the Morris water maze testing period; (3) group B, 30 days exercise before the Morris water maze testing period only; (4) group D, 8 days exercise only during the Morris water maze testing period. The results showed that chronic (30 days) and continuous (during 8 days of Morris water maze testing days) treadmill training produced a significant enhancement in spatial learning and memory which was indicated by decreases in path length and latency to reach the platform in the Morris water maze test (p<0.05). The benefits in these tests were lost in 3 days, if the daily running session was abandoned. In group D with acute treadmill running (8 days exercise only) the difference between the group A disappeared in 1 week and benefit seemed to be obtained in comparison with the controls without running program. In conclusion the chronic and daily running exercises promoted learning and memory in Morris water maze, but the benefits were lost in few days without daily running sessions in adult rats.     

Barriers of Adherence among Palestinian Healthcare Professionals towards the Protocol of Health Education and Counselling on Healthy Behaviours for Non-Communicable Diseases

BackgroundDespite the huge numbers of the universally produced and employed protocols, the adherence with them is still low to moderate in the healthcare settings. This study was employed to assess the attitudes of Palestinian healthcare professionals in Gaza Strip to health education and counseling on healthy behaviours protocol (WHO-PEN Protocol 2), for patients with non-communicable diseases in the Ministry of Health primary healthcare centers.MethodsThis cross-sectional study was conducted with a census sample of all governmental family physicians and nurses (n=175). The study questionnaire was developed based on Cabana theoretical framework. The Arabic version questionnaire was developed based on the cross-cultural adaptation framework. The psychometric properties of the Arabic version questionnaire was finally evaluated.ResultsThe psychometric properties of the Arabic version questionnaire showed good construct validity and internal consistency reliability. The overall adherence level to WHO-PEN Protocol 2 was 70.0, SD=6.9. The main perceived barriers were lack of incentive, patients'' factors, and lack of time. In general, most of healthcare professional respondents had a positive attitude toward the protocol, but this attitude was not predictor to protocol adherence.ConclusionThe good validity and reliability of the questionnaire can provide support for the accuracy of the study results. Varied implementation strategies targeting the major barriers derived from the study are extremely required for addressing the lack of incentives, patients'' factors and time constraints.     

Solution of a specific class of nonlinear fractional optimal control problems including multiple delays

This research provides a new framework based on a hybrid of block‐pulse functions and Legendre polynomials for the numerical examination of a special class of scalar nonlinear fractional optimal control problems involving delay. The concepts of the fractional derivative and the fractional integral are employed in the Caputo sense and the Riemann‐Liouville sense, respectively. In accordance with the notion of the Riemann‐Liouville integral, we derive a new integral operator related to the proposed basis called the operational matrix of fractional integration. By employing two significant operators, namely, the delay operator and the integral operator connected to the hybrid basis, the system dynamics of the primal optimal control problem converts to another system involving algebraic equations. Consequently, the optimal control problem under study is reduced to a static optimization one that is solved by existing well‐established optimization procedures. Some new theoretical results regarding the new basis are obtained. Various kinds of fractional optimal control problems containing delay are examined to measure the accuracy of the new method. The simulation results justify the merits and superiority of the devised procedure over the existing optimization methods in the literature.