Hafnium (IV) oxide obtained by atomic layer deposition (ALD) technology promotes early osteogenesis via activation of Runx2-OPN-mir21A axis while inhibits osteoclasts activity.

BACKGROUND: Due to increasing aging of population prevalence of age-related disorders including osteoporosis is rapidly growing. Due to health and economic impact of the disease, there is an urgent need to develop techniques supporting bone metabolism and bone regeneration after fracture. Due to imbalance between bone forming and bone resorbing cells, the healing process of osteoporotic bone is problematic and prolonged. Thus searching for agents able to restore the homeostasis between these cells is strongly desirable. RESULTS: In the present study, using ALD technology, we obtained homogeneous, amorphous layer of hafnium (IV) oxide (HfO2). Considering the specific growth rate (1.9Å/cycle) for the selected process at the temperature of 90 °C, we performed the 100 nm deposition process, which was confirmed by measuring film thickness using reflectometry. Then biological properties of the layer were investigated with pre-osteoblast (MC3T3), pre-osteoclasts (4B12) and macrophages (RAW 264.7) using immunofluorescence and RT-qPCR. We have shown, that HfO2 (i) enhance osteogenesis, (ii) reduce osteoclastogenesis (iii) do not elicit immune response and (iv) exert anti-inflammatory effects. CONCLUSION: HfO2 layer can be applied to cover the surface of metallic biomaterials in order to enhance the healing process of osteoporotic bone fracture.

Antiviral activity of an aqueous extract derived from Aloe arborescens Mill. against a broad panel of viruses causing infections of the upper respiratory tract.

BACKGROUND: A number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. But these therapies are very often of limited efficacy or have severe side effects. Therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin. HYPOTHESIS: Since an aqueous extract of Aloe arborescens Mill. shows antiviral activity against viruses causing infections of the upper respiratory tract in vitro we hypothesised that a product containing it such as Biaron C(®) could have an antiviral activity too. STUDY DESIGN: Antiviral activity of Bioaron C(®), an herbal medicinal product consisting of an aqueous extract of Aloe arborescens Mill., Vitamin C, and Aronia melanocarpa Elliot. succus, added as an excipient, was tested in vitro against a broad panel of viruses involved in upper respiratory tract infections. METHODS: These studies included human adenovirus and several RNA viruses and were performed either with plaque reduction assays or with tests for the detection of a virus-caused cytopathic effect. RESULTS: Our studies demonstrated an impressive activity of Bioaron C(®) against members of the orthomyxoviridae - influenza A and influenza B viruses. Replication of both analysed influenza A virus strains - H1N1 and H3N2 - as well as replication of two analysed influenza B viruses - strains Yamagatal and Beiying - was significantly reduced after addition of Bioaron C(®) to the infected cell cultures. In contrast antiviral activity of Bioaron C(®) against other RNA viruses showed a heterogeneous pattern. Bioaron C(®) inhibited the replication of human rhinovirus and coxsackievirus, both viruses belonging to the family of picornaviridae and both representing non-enveloped RNA viruses. In vitro infections with respiratory syncytial virus and parainfluenza virus, both belonging to the paramyxoviridae, were only poorly blocked by the test substance. No antiviral activity of Bioaron C(®) was detected against adenovirus - a non-enveloped DNA virus. CONCLUSIONS: These results represent the first proof of a selective antiviral activity of Bioaron C(®) against influenza viruses and create basis for further analyses of type and molecular mechanisms of the antiviral activity of this herbal medicine.

Prostaglandins and mechanisms of preterm birth.

Increased uterine contractility at term and preterm results first from activation and then stimulation of the myometrium. Activation can be provoked by mechanical stretch of the uterus, and by an endocrine pathway resulting from increased activity of the fetal hypothalamic-pituitary-adrenal axis. In sheep fetuses, increased cortisol output during pregnancy regulates expression of prostaglandin synthase type 2 (PGHS-2) in the placenta in an oestrogen-independent manner, resulting in increased concentrations of prostaglandin E2 (PGE2) in the fetal circulation. Later increases in maternal uterine expression of PGHS-2 require increases in oestrogen and lead to increased concentrations of PGF(2alpha) in the maternal circulation. Thus, regulation of PGHS-2 at term is differentially controlled in fetal (trophoblast) and maternal (uterine epithelium) tissue. This difference may reflect expression of glucocorticoid receptor but not oestrogen receptor (ER) in placental trophoblast cells. In women, cortisol also contributes to increased prostaglandin production in fetal tissues through upregulation of PGHS-2 (amnion and chorion) and downregulation of 15-OH prostaglandin dehydrogenase (PGDH; chorion trophoblasts). The effect of cortisol on expression of PGDH in the chorion reverses a tonic stimulatory effect of progesterone, potentially through a paracrine or autocrine action. In membranes, cortisol may be derived from cortisone through activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1, in addition to secretion from the maternal or fetal adrenal glands. In placenta, 11beta-HSD-2 oxidase activity predominates and expression of this enzyme is reduced with hypoxaemia and in placentae from pre-eclamptic pregnancies. In these circumstances, increased concentrations of maternal cortisol may cross into the fetal compartment, contributing to growth restriction and programming later life disease.

[Chylomicronemia syndrome in 45 years old man]. / Zespól chylomikronemii u 45-letniego mezczyzny.

The case of chylomicronemia syndrome in 45 year old man, previously misdiagnosed as hypercholesterolemia is described. Secondary causes of hyperlipoproteinemia were excluded. No symptoms, characteristic of familial lipoprotein lipase deficiency were observed. We concluded that the diagnosis of hyperlipoproteinemia has to be based on determination of all plasma lipids concentrations (total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol). Otherwise a false diagnosis is quite possible. In rare cases additional laboratory tests are needed.

[Influence of long-term low molecular weight heparin nebulization on selected clinical parameters and course of allergic inflammation in patients with bronchial asthma]. / Wplyw heparyny niskoczasteczkowej w przewleklej nebulizacji na wybrane parametry kliniczne i przebieg zapalenia alergicznego u pacjentów z astma oskrzelowa.

Bronchial asthma is a chronic condition with an inflammatory background--allergic inflammation. In recent years several observations have been published documenting activity of low molecular weight heparin (LMWH) in chronic inflammatory diseases of respiratory tract. This study was set up to evaluate the effect of nebulized LMWH on spirometric parameters and selected markers of allergic inflammation in bronchial asthma. Twenty patients diagnosed with mild or moderate asthma entered the study. At the beginning and at the end of the experiment every patient underwent bronchoscopy with BAL and in 15 of them bronchial biopsy was performed. Blood was drawn for ECP evaluation. LMWH was administered in nebulization in a dose 5000 U Xa/day for two weeks. BALf cellularity was evaluated as well as BALf IL-5 concentration. Further ELAM-1 and VCAM-1 expression in bronchial mucosa was examined in immunohistochemistry. We demonstrated that heparin treatment significantly enhanced FEV1 from 76.02 +/- 21.7% nominate value before to 92.4 +/- 21.8% after treatment (p < 0.005). Cellular profile of BALf changed, showing significant drop in percentages of eosinophils--from 7% to 6% (p < 0.05), macrophages--38 to 32% (p < 0.05) and neutrophils--32 to 28% (p < 0.05). Surprisingly we did not notice any change in ECP concentration in blood serum or IL-5 in BALf. Also adhesion molecules expression in bronchial mucosa remained unchanged. We conclude that chronic LMWH nebulization is a valuable treatment ameliorating asthmatic condition clearly due to anti-inflammatory properties of heparin. Both dose of LMWH used and the time of therapy have to be further investigated in order to develop treatment able to influence more of the elements of allergic inflammation.

[Evaluation of effectiveness and safety of three year immunotherapy with mixed grass pollen allergens]. / Ocena skutecznosci klinicznej i bezpieczenstwa trzyletniej immunoterapii mieszanka alergenów pylków traw.

BACKGROUND: Specific immunotherapy (SIT) is probably the only causative treatment in allergic diseases including pollinosis. It is capable of changing the natural history of the disease. GOAL: Present study has been designed to estimate the effectiveness and safety of multi-seasonal immunotherapy with grass-pollen-allergoid-containing vaccines. MATERIAL AND METHODS: Twenty seven patients with pollinosis entered the study. They were randomly assigned to two groups receiving two different but absolutely comparable vaccines (Allergovit, Pollinex). Cards of patient's self-evaluation (including nasal, eye and bronchial symptoms) as well as anti-allergic drug consumption were evaluated. RESULTS: Significant amelioration of symptoms was noticed already after first season of SIT 3.4 +/- 0.29 vs 7.54 +/- 0.35 points before SIT (control)(p < 0.05). The respective value after third SIT was 2.1 +/- 0.26 (p < 0.001). Also anti-allergic drug consumption felt from 2.12 +/- 0.12 points before SIT to 0.86 +/- 0.11 and 0.37 +/- 0.11 after first and third SIT, respectively (p < 0.001 and p < 0.00005). Few side reactions were observed, only one mild systemic reaction. CONCLUSIONS: Our study confirms that pre-seasonal SIT is a clinically effective and safe therapeutic method in patients with pollinosis. It's effect seems to be time-related.

Differential regulation of epithelial-derived C-C chemokine expression by IL-4 and the glucocorticoid budesonide.

Airway epithelial cells are a rich source of eosinophil-selective C-C chemokines. We investigated whether cytokines and the topical glucocorticoid budesonide differentially regulate RANTES, monocyte chemoattractant protein-4 (MCP-4), and eotaxin mRNA and protein expression in the human bronchial epithelial cell line BEAS-2B and in primary human bronchial epithelial cells by Northern blot analysis and ELISAs. Eotaxin and MCP-4 mRNA expression induced by TNF-alpha alone or in combination with IFN-gamma was near-maximal after 1 h, peaked at 4 and 8 h, respectively, remained unchanged up to 24 h, and was protein synthesis independent. In contrast, RANTES mRNA was detectable only after 2 h and slowly increased to a peak at 24 h, and was protein synthesis dependent. Induction of eotaxin and MCP-4 mRNA showed a 10- to 100-fold greater sensitivity to TNF-alpha compared with RANTES mRNA. IL-4 and IFN-gamma had selective effects on chemokine expression; IL-4 selectively up-regulated the expression of eotaxin and MCP-4 and potentiated TNF-alpha-induced eotaxin, while IFN-gamma markedly potentiated only the TNF-alpha-induced expression of RANTES. Although budesonide inhibited the expression of chemokine mRNA to a variable extent, it effectively inhibited production of eotaxin and RANTES protein. Budesonide inhibited both RANTES- and eotaxin promoter-driven reporter gene activity. Budesonide also selectively accelerated the decay of eotaxin and MCP-4 mRNA. These results point to IL-4 as a possible mediator by which Th2 cells may induce selective production of C-C chemokines from epithelium and indicate that glucocorticoid inhibit chemokine expression through multiple mechanisms of action.

Effect of heparin on the course of sulphur dioxide induced bronchitis in rats.

The aim of this study was to investigate the effect of heparin on the rat bronchial mucosa changes induced by sulphur dioxide (SO2) inhalation. Sixty five rats were used in this experiment. Five of them constituted a control group, while 60 were exposed to SO2. Forty of the latter subgroup were additionally treated with low molecular weight heparin (LMWH), either during or after terminating exposure to SO2. In all animals exposed to SO2 inflammatory cells were found in broncho-alveolar lavage fluid (BALf) in numbers significantly higher from those observed in healthy controls. The rats exposed to SO2 and treated with LMWH showed intermediate cell pattern in the bronchi between healthy and SO2- exposed animals. When comparing histological picture of the bronchi, we noted extensive changes in irritated rats. These changes were either less expressed or totally absent in animals treated with heparin. The activity of enzymes: acid phosphatase (ACP), alkaline phosphatase (AP) and lactate dehydrogenase (LDH) rose in BALf, although the rise was not parallel and did not correlate with the magnitude of cellular influx or histological changes. Heparin did not influence this changes.

[Peripheral blood eosinophilia in patients with bronchial asthma before and after bronchial provocation]. / Eozynofilia krwi obwodowej u chorych na astme oskrzelowa przed i po swoistej prowokacji oskrzeli.

The study was set up in order to check the usefulness of peripheral blood eosinophilia in asthma diagnosis and asthma therapy monitoring. Twenty mild asthmatics entered the study--ten atopic and ten nonatopic. Eosinophilia was estimated twice: on the day of admission and twenty four hours after bronchial provocation. Bronchial hyperreactivity was measured on both occasions. We showed, that there was no difference in eosinophilia between atopic and nonatopic subjects before provocation but the difference was significant 24 hrs after provocation. In both groups of asthmatics eosinophilia correlated with bronchial hyperreactivity before and after provocation. We concluded, that eosinophilia is an easy and valuable parameter in monitoring the degree of allergic inflammation in asthmatics.

[Evaluation of allergic inflammation parameters in bronchoalveolar lavage in patients with asthma]. / Ocena parametrów zapalenia alergicznego w popluczynach oskrzelowych u chorych na astme.

The study was set up to evaluate the changes in broncho-alveolar lavage cell-count in asthmatics after bronchial provocation. Similarities and differences between atopic (A) and nonatopic (N) asthma were given a special concern. Twenty mild asthmatics--10 A and 10 N. There was no difference in BAL eosinophila between these groups before provocation. After provocation more eosinophils were found in A group (p = 0.06). Neutrophils were more numerous in N on both occasions--0 = 0.00003 and p = 0.006 respectively). Lymphocytes showed a similar pattern--p = 0.03, p = 0.003. A positive correlation between BAL eosinophilia and bronchial hyperreactivity was shown in both groups. Inflammation, including inflammatory cells plays a major role in bronchial asthma pathophysiology. It seems to be more expressed in nonatopic patients.

[Allergic bronchitis in bronchial asthma]. / Zapalenie alergiczne w astmie oskrzelowej.

Asthma was known already in ancient times. International Consensus Report on Diagnosis and Management of Asthma published in 1993 gives its updated definition, classification and treatment, but pathomechanism and pathophysiological differences between atopic and non-atopic asthma remain unclear. Most commonly accepted is the inflammatory conception of asthma presented by Kay in 1983. Eosinophil, lymphocyte and their products seem to play an important role in allergic inflammation. A raise of interest toward adhesion molecules role has been observed lately.

[Evaluating the safety of bronchoalveolar lavage in patients with bronchial asthma in light of gasometric and spirometric examinations]. / Ocena bezpieczenstwa plukania oskrzelowo-pecherzykowego u chorych na astme oskrzelowa w swietle badan gazometrycznych i spirometrycznych.

Gasometric parameters were performed before, during and after bronchoalveolar lavage (BAL) in 21 patients with mild bronchial asthma. In addition, spirometric parameters were performed before and after BAL. Decrease of pO2, SaO2 and increase of pCO2 which kept within the limits of normal values were observed. After BAL gasometric parameters returned to baseline values. Bronchoalveolar lavage caused statistically significant fall in FEV1 and PEF. BAL was well tolerated and did not worse the clinical state of patients.

[Current views on the pathogenesis and treatment of pulmonary emphysema and chronic bronchitis]. / Wspólczesne poglady na patogeneze i leczenie rozedmy pluc i przewleklego zapalenia oskrzeli.

In recent years a rising interest has developed among the authors studying the problems of pathogenesis and treatment of chronic bronchitis and pulmonary emphysema in the factors responsible for the immune equilibrium of the respiratory system. In particular, the correlation has been stressed between the levels of inflammation mediators and the activity of proteolytic enzymes and their inhibitors in lung tissue. Most studies seem to confirm the validity of the elastase-antielastase concept. Among the environmental factors directly responsible for the development of these diseases tobacco smoke and other irritant fumes (SO2NO2) are mentioned. This concept had been the foundation for trials of therapeutic use of inhibitors of elastolytic enzymes.

The efficacy of computed tomography in evaluating abdominal injuries in children with major head trauma.

Physical examination may be unreliable in the evaluation of children with blunt abdominal trauma particularly in those with associated major head injuries. In the absence of obvious clinical signs or physical findings of intraabdominal injury, the usefulness of abdominal computed tomography in children is controversial. To test the efficacy of CT scans, a 12-month prospective study of computed tomography for the initial assessment of children with blunt abdominal trauma and major head injuries was carried out. Of 320 pediatric trauma admissions to our regional trauma center, 65 consecutive patients with Glasgow Coma Scores less than ten were managed with sequential head and abdominal computed tomography in the emergency room for (1) closed head injury and (2) suspected abdominal trauma. Fifteen patients (23%) were found to have significant intraabdominal injury. Only two required operative intervention. No patients died as a result of the abdominal injuries. In children with significant head trauma and suspected abdominal trauma, combined head and abdominal CT proved to be reliable.