Melatonin treatment prevents carbon tetrachloride-induced acute lung injury in rats by mitigating tissue antioxidant capacity and inflammatory response.

AIM: Carbon tetrachloride (CCl4) is an organic chemical that produces different tissue­damaging effects when ingested or inhaled. Present study aims to determine whether the application of exogenous melatonin, a neurohormone with numerous biological properties, can prevent disturbances in lung tissue antioxidative capacities and arginine metabolism, tissue inflammation and oxidative damage induced by exposure to CCl4 in rats. METHODS: The effects of melatonin on the changes occurring in rat lung tissue after an acute exposure to CCl4 were studied by monitoring alterations in antioxidant capacities, inflammatory parameters, parameters of arginine metabolism, and lipid and protein oxidative damage. RESULTS: The results indicated that melatonin prevents CCl4-induced lung damage by mitigating tissue antioxidant capacity and preventing nitric oxide production through a shift from nitric oxide synthase to arginase. Also, melatonin partially prevented tissue inflammation and molecules' oxidative modification seen after exposure to CCl4. CONCLUSIONS: The protective activity of melatonin can be attributed to its ability to scavenge both free radicals, as well as to its potential to increase tissue antioxidant capacity. The modulation of inflammatory response through both decrease in tissue inflammatory parameters and influence on arginine-nitric oxide metabolism might be an additional mechanism of action (Tab. 1, Fig. 2, Ref. 33).

Effects of specific allergen immunotherapy on biological markers and clinical parameters in asthmatic children: a controlled-real life study.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy). METHODS: 7-18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up. RESULTS: There was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation. CONCLUSIONS: Our data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed.

Musculoskeletal Pain and Vitamin D Deficiency in Children: A Pilot Follow-up Study of Vitamin D Therapy in Musculoskeletal/Orthopedic Conditions.

PURPOSE OF THE STUDY: The prevalence of vitamin D deficiency in pediatric populations is high. In the present study we analyzed associations between vitamin D therapy and pain, mobility, fatigue, and daily functioning in children with musculoskeletal/orthopedic conditions suffering from chronic and recurrent pain, but also diagnosed with vitamin D deficiency. MATERIAL AND METHODS: Children with different musculoskeletal/orthopedic conditions and vitamin D deficiency were prescribed to receive vitamin D over 6 months. Thirty-five children (18 males; age 10.48 ± 3.87 years) completed a 6-month follow-up. Self- and parent/proxy rating scales were used to evaluate pain, movement, fatigue, and daily functioning. RESULTS: At a six-month follow-up assessment involving child- and parent-reported scores, worst pain intensity significantly decreased (p ≤ 0.03) after vitamin D therapy, as well as functioning problems related to pain (p ≤ 0.01). The children reported better movement and balance with less fatigue. The parents reported better functioning in everyday activities of their children. CONCLUSION: This pilot study showed that vitamin D therapy possibly reduces pain intensity and improves mobility and daily functioning in children with musculoskeletal/orthopedic disorders, chronic recurrent pain, and vitamin D deficiency. Further follow-up and randomized studies are required in order to assess the validity of clinical recommendations.

The correlation between parental education and their knowledge of asthma.

OBJECTIVE: To evaluate the impact of parental education on the success of Asthma Educational Intervention (AEI). METHODS: AEI took place after the children's hospitalisation. Parental asthma knowledge was assessed at three time points: before AEI, immediately after, and 12 months later. The Intervention (I) group of parents (N=231) received complete AEI. The Control (C) group of parents (N=71) received instructions for proper use of asthma medications and the handbook. RESULTS: Asthma knowledge in I group increased immediately after the AEI (p<0.01), and had not changed (p>0.05) 12 months later. There were four subgroups in group I divided based on education level: elementary school, high school, college, and university degrees. Taking into account the parental education level, there were no differences in the baseline and final knowledge of asthma between subgroups (p>0.05). The number of asthma exacerbations decreased after AEI (5.96:2.50, p<0.01), regardless of the parental degree. Knowledge of asthma in group C did not improve during the study (p=0.17). Final asthma knowledge was higher in group I compared to group C (p<0.01). CONCLUSION: The parental education level did not influence the level of asthma knowledge after the AEI. The motivation and the type of asthma education had the greatest input on the final results. PRACTICE IMPLICATIONS: All parents should be educated about asthma regardless of their general education.

Propagation of a Brazilian isolate of Anaplasma marginale with appendage in a tick cell line (BME26) derived from Rhipicephalus (Boophilus) microplus.

Anaplasma marginale is a tick-borne pathogen of cattle responsible for the disease anaplasmosis. Data suggest that Rhipicephalus (Boophilus) microplus and R. annulatus may be the major tick vectors of A. marginale in tropical and subtropical regions of the world. In this work we demonstrated the first infection and propagation of a Brazilian isolate of A. marginale (UFMG1) in the BME26 cell line derived originally from embryos of R. (Boophilus) microplus. The establishment of A. marginale infection in a cell line derived from R. (Boophilus) microplus is relevant for studying the A. marginale/tick interface.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Uptake of gallium-67 by human leukemic cells: demonstration of transferrin receptor-dependent and transferrin-independent mechanisms.

We have studied the role of transferrin and the transferrin receptor in the uptake of 67Ga by the human leukemic cell line HL60. In the absence of transferrin, HL60 cells incorporated about 1% of the 67Ga dose over 6 h. The presence of transferrin increased cellular 67Ga uptake approximately 10-fold. Transferrin-mediated uptake of 67Ga was blocked by an anti-transferrin receptor monoclonal antibody, and decreases in the density of cellular transferrin receptors led to corresponding decreases in the transferrin-dependent uptake of 67Ga. Changes in the cellular ferritin content did not significantly influence the uptake of 67Ga by either transferrin-independent or transferrin-dependent pathways. Regardless of the mechanism of uptake, a significant amount of intracellular 67Ga was found to be associated with immunoprecipitable ferritin as well as with a free pool. This free intracellular 67Ga appeared to be kinetically active since cells released 67Ga back to the media over time. Our results demonstrate the existence of a dual mechanism for the cellular uptake of 67Ga and suggest that the preferential uptake of 67Ga by lymphomas is related to the high density of transferrin receptors known to be expressed by these tumors in vivo.

Measurement and simulation of unmyelinated nerve electrostimulation: Lumbricus terrestris experiment and numerical model.

The electrostimulation excitation threshold of a nerve depends on temporal and frequency parameters of the stimulus. These dependences were investigated in terms of: (1) strength-duration (SD) curve for a single monophasic rectangular pulse, and (2) frequency dependence of the excitation threshold for a continuous sinusoidal current. Experiments were performed on the single-axon measurement setup based on Lumbricus terrestris having unmyelinated nerve fibers. The simulations were performed using the well-established SENN model for a myelinated nerve. Although the unmyelinated experimental model differs from the myelinated simulation model, both refer to a single axon. Thus we hypothesized that the dependence on temporal and frequency parameters should be very similar. The comparison was made possible by normalizing each set of results to the SD time constant and the rheobase current of each model, yielding the curves that show the temporal and frequency dependencies regardless of the model differences. The results reasonably agree, suggesting that this experimental setup and method of comparison with SENN model can be used for further studies of waveform effect on nerve excitability, including unmyelinated neurons.

Cytotoxicity of commonly used nitroxide radical spin probes.

Since nitroxide radical spin probes are used frequently to test biophysical properties of cells, their use should be restricted to conditions that do not perturb normal cell growth and viability. Eight commonly used nitroxide radical spin probes have been tested for their effects on the survival of CHO cells. These include water-soluble spin probes Tempol, Tempamine, CTPO, CTPC and 4-maleimido-Tempo, and lipid soluble spin probes 5-Doxyl-, 12-Doxyl-, and 16-Doxylstearates. With the exception of 4-maleimido-Tempo, none of the water soluble spin labels inhibited cell survival at concentrations as high as 1 mM. At concentrations of 75 microM and higher, 4-maleimido-Tempo inhibited cell survival in a dose dependent manner. At concentrations commonly used for spin labeling of cells (30-50 microM) none of the lipid soluble spin probes tested was cytotoxic. At 100 microM only 5-Doxylstearate inhibited cell survival, whereas 12-Doxylstearate and 16-Doxylstearate had no effect.

Exposure to tobacco smoke among asthmatic children: parents' smoking habits and level of education.

SETTING: Children's Hospital for Respiratory Diseases and Tuberculosis, Belgrade, Serbia. OBJECTIVES: To compare parents' educational level and smoking habits with asthma in children exposed to environmental tobacco smoke (ETS) and in those not exposed. METHODS: In this cross-sectional study, 231 asthmatic children (average age 10.6 years, 49% boys) from smoking and non-smoking families were compared by birth weight, birth length, first episode of wheezing, number of respiratory infections and exacerbations per year, severity of asthma, number of hospitalisations, total serum immunoglobulin E (IgE), skin prick tests and allergic manifestations. RESULTS: In our study, 77% of the children were from smoking families: 45.9% had active smoking mothers and 51% active smoking fathers. Smoking was more common among parents with lower education level. The mother being the only smoker in the family had a greater impact on respiratory infections and asthma exacerbations in the first years of life; however, after the third year, the effect of having both smoking parents was important. Children exposed to ETS had more allergic manifestations. The percentage of children with both non-smoking parents decreased and that of children with both smoking parents increased with increasing asthma severity (χ(2) = 17.73, P < 0.05). CONCLUSION: ETS has a negative impact on illness among children with asthma.

[Congenital club foot].

Congenital club foot is the most frequent foot deformity. It occurs in 1% of newborns, two times more frequently in boys, with family inheritance. Patoanatomicaly, entity consists of bone deformities, articular malpositions and soft tissues retraction. All these produce adduction of the forefoot and varus and equinovarus of the hindfoot. Lateral side of the foot is convex and medial side is concave. Forefoot is in adduction and plantar flexion in relation to the hindfoot. The heel is rotated medialy which induces varus and eqinus of the foot. The aim of the treatment is to establish anatomically normal foot, painless, with moderate movements, which is suitable for normal shoes. At the beginning treatment is nonsurgical. If nonsurgical treatment fails further step should be surgical treatment. The success of treatment of congenital clubfoot depends on the time of diagnosis and treatment beginning.

Inhibition of hemoglobin production by transferrin-gallium.

Recent clinical trials evaluating gallium nitrate as a chemotherapeutic agent have reported the development of microcytic hypochromic anemia in patients treated with this agent. Because gallium is known to bind avidly to transferrin, we examined the effect of transferrin-gallium (Tf-Ga) on hemoglobin production by Friend erythroleukemia cells in vitro. Cellular hemoglobin production, as assessed by benzidine staining, cellular hemoglobin content, and 59Fe incorporation into heme, was significantly decreased following exposure of cells to Tf-Ga. Tf-Ga led to an early decrease in cellular 59Fe incorporation even before changes in hemoglobin production were detected. A marked increase in cellular transferrin receptor expression occurred following exposure of cells to Tf-Ga. Tf-Ga inhibition of hemoglobin production could be reversed and hemoglobin production could be restored to normal by addition to the media of either transferrin-iron (Tf-Fe) or iron-pyridoxal isonicotinoyl hydrazone, a compound capable of supplying iron directly to reticulocytes for heme synthesis without transferrin as a mediator. These studies provide an explanation for the development of anemia in patients treated with gallium nitrate and suggest that gallium's mechanism of chemotherapeutic action includes inhibition of cellular iron incorporation.

Release of soluble transferrin receptor from the surface of human leukemic HL60 cells.

Information regarding transferrin (Tf) receptor degradation is largely incomplete. HL60 cells were shown to release to their growth medium a Tf-binding protein which could be immunoprecipitated by anti-Tf receptor monoclonal antibodies (MoAbs) B3/25 and OKT9. Soluble Tf receptor was detected in the medium within one hour of replating of cells, and its release was inhibited at 4 degrees C. The affinity of Tf for the soluble receptor released by cells (kd = 2.3 x 10(-10) mol/L) was slightly lower than its affinity for the detergent-solubilized cellular receptor (kd = 1.2 x 10(-10) mol/L). 125I-Tf internalized and released by cells subsequently bound to Tf receptor released by the same cells, and soluble Tf receptor in the conditioned medium (CM) inhibited 125I-Tf binding to intact cells. The soluble Tf receptor isolated from the CM was smaller (78,000 daltons) than the cell surface receptor (94,000 daltons) when analyzed by gel electrophoresis under reducing conditions. Isolated cell membranes readily released soluble receptor; however, this release could be blocked by protease inhibitors. The soluble Tf receptor may represent the extracytoplasmic domain of the cellular Tf receptor released from the surface of HL60 cells through proteolytic cleavage by a membrane-based protease.

[Angle between occlusal plane and horizontal plane of articulators with quick mounting face bow]. / Nagib protetske plohe u odonosu na horizontalu artikulatora s obraznim lukom za brzu montazu.

Correct determination of the occlusal plane is important for estetic, phonetic and masticatory function of the denture. As many different criterias are used in clinical practice to determine the occlusal plane on the wax rims, the aim of this study was to find the angle between the occlusal plane and the horizontal plane in the articulators with the quick mounting face bow. The measurements were made on the casts of 30 eugnath individuals with at least 28 natural teeth, mounted in S.A.M. articulator through the transfer with the Quick mounting face bow, in the position of maximum intercuspation. Measurements were made with a precise caliper and were transferred to the calibrated paper. The angles were measured between the occlusal plane and the horizontal plane. The angle is 9.42 degrees +/- 4.1 degrees in the population of this country. This result can be helpful to determine the occlusal plane or to control if the occlusal plane, determined by the other methods is in the correct position in articulator.

A case of McLeod syndrome with chronic renal failure.

A 50-year-old man with the rare McLeod syndrome, associated with glomerular lesion to the end stage of chronic renal failure and death, is reported. McLeod syndrome is an X-linked recessive disorder on the basis of abnormal expression of the Kell blood group antigens and absence of erythrocyte surface Kx antigen. Most often the clinical and pathological findings are retinitis pigmentosa to blindness, progressive chronic neuropathy, cortical atrophy, dilated cardiomyopathy, and glomerular lesion with chronic renal failure. Among the laboratory parameters the most important are very low level of cholesterol and triglycerides, then various numbers of acanthocytes in peripheral blood smears and sometimes in urine (as in our case).