Radiation therapy in treatment of fibrodysplasia ossificans progressiva: a case report and review of the literature

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic disorder with diffuse extra-skeletal bone formation. The genetic mutation responsible for FOP has recently been discovered and is connected with excessive activation of bone morphogenetic protein receptor. This disease usually begins with typical ossification pattern in early childhood, causing increasing disability and making patients totally disabled by the age of 30. Ectopic ossification develops spontaneously and can be triggered by any trauma and even intramuscular injections. The symptoms of FOP are often misdiagnosed as cancer, causing unnecessary biopsies, which can precipitate further progressive heterotopic ossification. There is no effective treatment for this severe condition. Radiotherapy can be helpful in impeding ossification, although the strict evidence for that is lacking. There are only two reports in the literature referring to the use of radiotherapy in treatment of FOP. Herein, we present a 35-year-old patient successfully treated with small doses of fractionated radiotherapy in several courses. This case indicates that radiotherapy can be useful in treating patients with FOP.     

Oxidative stress markers in patients with post-traumatic stress disorder

Recent study data support the role of oxidative stress in diverse psychiatric disorders. Oxidative stress results from an oxidant/antioxidant imbalance, an excess of oxidants and/or a depletion of antioxidants. There are numerous studies that indicate that free radicals (FRs) damage neurons, and then play an important role in the pathophysiology of schizophrenia and depression. Active oxygen can cause considerable damage and disrupt the important physiological functions of proteins, lipids, enzymes and DNA. The aim of our study was to investigate the possible differences in the concentration of tromboxane B2, 8-OHdG and protein carbonyls, as significant markers of oxidative damage, and urate, albumin and total protein concentrations as antioxidative molecules in PTSD patients in comparison to the healthy control group. The study included 74 male participants who were active soldiers in the Croatian armed forces from 1991 to 1995. 46 subjects with chronic and current PTSD were recruited from the Department of Psychiatry of Dubrava University Hospital during 2010, 28 healthy subjects were recruited in the same period during the regular medical examination at the Dubrava University Hospital. Study results have shown that there is no statistically significant difference in urinary concentrations of 8-OHdG, serum thromboxane B2, and serum urates between two studied groups. Statistically significant difference of the protein carbonyl concentrations was examined. Concentrations were significantly lower in the PTSD group than in the control group. The clinical significance of these results was examined using ROC analysis. The obtained ROC curves did not separate the groups in a satisfactory manner.     

Importance of circulating platelet aggregates and haemodynamic changes in ophthalmic artery and progression of visual field loss at pseudoexfoliation glaucoma

The aim of this work is to examine the role of circulating platelet aggregates (CPA) at pseudoexfoliation glaucoma (PXG), haemodynamic changes in the ophthalmic artery by ultrasonic color Doppler, searching for visual field progression. Vascular component at PXG and its role in VF progression dynamics has not been sufficiently explained, as well as CPA influence to ischaemic events related to optic nerve damage and VF progression. The examination included 80 patients, where of 35 (44%) men average age 68.3 +/- 7.0 and 45 (56%) women average age 65.7 +/- 7.0 (t = 1.66; p = 0.101). Forthy of them suffered from primary open angle glaucoma (POAG) as a control group (healthy), and 40 from pseudoexfoliative glaucoma (PXG) as an experimental group. All the examinees underwent complete ophthalmological examination: visual acuity, ocular fundus, intraocular pressure measured, anterior eye segment biomicroscopy with gonioscopy performed. Also VF examination was performed three times at 6 months intervals. Laboratory testing of CPA proportion values was performed by means of Wu an Hoak method and ultrasonic measurement of blood perfusion in the carotid tree, particularly concerning ophthalmic artery by means of color Doppler. Obtained decreased values of CPA proportion resulted in hypercoagulability of blood in PXG group. At PXG were also found increased blood flow resistivity indexes in ophthalmic artery (RI AO) and internal carotid artery (RI ACI), resulting with ischemia and hypoxia and finally progression of the visual filed damage. In conclusion, our study shows that examining CPA and ultrasonic monitoring of vascular parameters in ophthalmic artery with color Doppler may be the way of better understanding the vascular role in PXG prognosis.     

The etiological relation between serum iron level and infection incidence in hemodialysis uremic patients

Through the treatment of anaemia in dialysis patients part of the iron ions remain free in the serum which is at the bacterias disposal for growth and the strengthening of their virulence. The linear relation of the increased serum iron level and tissue iron stores in the body and the infection incidence in dialysed patients has become more emphasised. The need of a clearly defined upper threshold of the serum iron concentration limit has been mentioned in scientific journals intensely, and consequently the demand for more precise professional instructions for anaemia treatment. For the purpose of participating in these professional and scientific discussions, we have observed the relation between the iron overload of the organism and complication incidence in 120 of our haemodialysis uremic patients, with special emphasis on infections. It has been established that the sepses incidence is much higher in patients with a serum ferritin concentration above 500 microg/L, than in those patients with a ferritin level lower than the mentioned value ( 2 = 7.857, p = 0.005). The incidence of vascular access infection is significantly higher in those patients with a serum ferritin level above 500 microg/L than in those patients with a ferritin level lower than the mentioned value (Chi2 = 23.186, p = 0.001). Furthermore, it has been determined that the incidence of total infection in patients is 3.8 episodes per 100 patients months, which is in accordance to the referral values of other authors. CONCLUSION--In the analysis of the achieved results, it has been determined that the infection incidence is significantly higher in dialysed patients with a serum iron level higher than 500 g/L, than in those patients with lower values.     

The validity of ESIN method of osteosynthesis compared to other active surgical methods of treatment of diaphyseal fractures of long bones in children and adolescents

We investigated the relationship of efficiency in the application of the ESIN method of intramedullary osteosynthesis and other active surgical methods in the treatment of diaphyseal fractures of long bones in children and adolescents. The study comprised 100 subjects treated by elastic stable intramedullary osteosynthesis (ESIN - group A) and 50 subjects in whom other active surgical methods were applied (group B). The following criteria of efficiency of treatment were applied: 1. length of perioperative hospitalization, 2. time elapsed since the operation until the beginning of loading of the traumatized extremity, 3. time elapsed since the operation until the full loading of the extremity, i.e. until the recovery of the fracture, 4. incidence of complications, 5. number of post-operative outpatient clinical visits until the recovery of the fracture and 6. overall number of X-ray images of the fractured bone since the accident until the coalescence of the fracture. The results obtained in both groups were compared. 1. The length of perioperative hospitalization is shorter in patients in whom ESIN method was applied. The difference between arithmetic means was 4.45 days and is statistically significant (p < 0.001). 2. The time between the operation until the beginning of loading of the extremity is shorter in patients subjected to ESIN method of osteosynthesis, the difference of mean values being 23.49 days and is statistically significant (p < 0.001). 3. The time between the operation until the full loading of the extremity is shorter in patients subjected to ESIN method of osteosynthesis, the difference being 16.6 days and is statistically significant (p < 0.001). 4. The number of complications in patients treated by the ESIN method of osteosynthesis is not statistically different from that in group B (chi2 = 0.25, p = 0.62). 5. In postoperative period there were fewer outpatient controls in patients to whom ESIN method of osteosynthesis was applied, and the difference is statistically significant (Z = 7.69, p < 0.001). 6. Likewise, the overall number of X-ray controls was lesser (Z = 8.06, p < 0.001). The results of examining the above parameters point to a greater efficiency of treating diaphyseal fractures of long bones in children and adolescents by the ESIN method of osteosynthesis, compared to other active surgical methods.     

Low dose computerized tomography examinations of coronary occlusive disease

Background: The aim of this study was to present an original technique of low-dose coronary computerized tomographyangiography (CCTA) for the evaluation and early diagnosis of coronary occlusive disease (COD) and to compare from this technique of CCTA with those resulting from the latest conventional angiography and multidetector computerized tomography units. Methodology: The study included 820 CCTA exams of patients with COD (average age 61 +/? 7 years), with a follow-up exam in 204 male (39%) and 62 female (20%) patients with hemodynamically insignificant coronary occlusion. Exams were performed using a 64-slice computerized tomography (CT) unit using electrocardiography (ECG)-triggering and individual settings (voltage of the x-ray tube and effective tube-current) based on each patient’s body mass index. Exponential dose for each exam was defined. Results:There was a statistically significant progression in the number of patients in whom occlusion of one of 3 coronary arteries occurred in hemodynamically significant occlusive disease (occlusion of more than 50% of lumen) — 60 of 204 males and 12 of 62 females (p<0.0001 and p<0.001). The mid-effective radiation dose during CCTA exams was 1.9+/-0.7mSv (range of 0.9 to 3.9 mSv). Conclusion: Prospective ECG-triggering allowed for low-dose CCTA exams while still enabling high diagnostic accuracy in evaluating patients with COD. The technique used in this study resulted in 2 times less the exponential dose than conventional angiography.     

H1 RNA polymerase III promoter-driven expression of an RNA aptamer leads to high-level inhibition of intracellular protein activity

Aptamers offer advantages over other oligonucleotide-based approaches that artificially interfere with target gene function due to their ability to bind protein products of these genes with high affinity and specificity. However, RNA aptamers are limited in their ability to target intracellular proteins since even nuclease-resistant aptamers do not efficiently enter the intracellular compartments. Moreover, attempts at expressing RNA aptamers within mammalian cells through vector-based approaches have been hampered by the presence of additional flanking sequences in expressed RNA aptamers, which may alter their functional conformation. In this report, we successfully expressed a ‘pure’ RNA aptamer specific for NF-κB p50 protein (A-p50) utilizing an adenoviral vector employing the H1 RNA polymerase III promoter. Binding of the expressed aptamer to its target and subsequent inhibition of NF-κB mediated intracellular events were demonstrated in human lung adenocarcinoma cells (A549), murine mammary carcinoma cells (4T1) as well as a human tumor xenograft model. This success highlights the promise of RNA aptamers to effectively target intracellular proteins for in vitro discovery and in vivo applications.     

Estrone derived steroidal diepoxide: Biologically active compound and precursor of a stable steroidal A,B-spiro system

A simple approach to a stable steroidal estrone derived A,B-spiro system is reported. Treatment of estrone derived A-ring diepoxyalcohol with the Ac₂O–TMSOTf system at the ambient temperature led to acetylation, while at the reflux temperature the acid-catalysed rearrangement took place affording the spiro-compound. Results of extensive in vitro and in vivo anticancer tests on the diepoxide, as well as preliminary data on the antiproliferative activity of the spiro-product against three cancer cell lines, are also presented.     

Exercise-induced intrapulmonary shunting of venous gas emboli does not occur after open-sea diving.

Paradoxical arterializations of venous gas emboli can lead to neurological damage after diving with compressed air. Recently, significant exercise-induced intrapulmonary anatomical shunts have been reported in healthy humans that result in widening of alveolar-to-arterial oxygen gradient. The aim of this study was to examine whether intrapulmonary shunts can be found following strenuous exercise after diving and, if so, whether exercise should be avoided during that period. Eleven healthy, military male divers performed an open-sea dive to 30 m breathing air, remaining at pressure for 30 min. During the bottom phase of the dive, subjects performed mild exercise at approximately 30% of their maximal oxygen uptake. The ascent rate was 9 m/min. Each diver performed graded upright cycle ergometry up to 80% of the maximal oxygen uptake 40 min after the dive. Monitoring of venous gas emboli was performed in both the right and left heart with an ultrasonic scanner every 20 min for 60 min after reaching the surface pressure during supine rest and following two coughs. The diving profile used in this study produced significant amounts of venous bubbles. No evidence of intrapulmonary shunting was found in any subject during either supine resting posture or any exercise grade. Also, short strenuous exercise after the dive did not result in delayed-onset decompression sickness in any subject, but studies with a greater number of participants are needed to confirm whether divers should be allowed to exercise after diving.     

Photosynthetic oxygen evolution and chlorophyll fluorescence in intact isolated chloroplasts on a solid support: the influence of orthophosphate

We devised recently a method to trap intact isolated chloroplasts on a solid support consisting of membrane filters made of cellulose nitrate (Cerovi et al., 1987, Plant Physiol. 84, 1249–1251). The addition of alkaline phosphatase to the reaction medium enabled continuous photosynthesis by spinach (Spinacia oleracea L.) chloroplasts to be sustained by hydrolysis of newly produced and exported triose phosphates and recycling of orthophosphate. In this system, simultaneous measurements of chlorophyll fluorescence and oxygen evolution were performed and their dependence on orthophosphate concentration was investigated. Optimal photosynthesis was obtained at a much higher initial orthophosphate concentration (2–4 mM) compared to intact chloroplasts in suspension. Secondary kinetics of chlorophyll fluorescence yield were observed and were shown to depend on the initial orthophosphate concentration.Abbreviations Chl chlorophyll - CSS intact isolated chloroplasts on solid support - ICS intact isolated chloroplasts in suspension - P_i orthophosphate - v rate of O₂ evolution - PPFD photosynthetic photon flux density The authors wish to thank Dr. Marijana Plesniar, from the University of Novi Sad, for stimulating discussions. This work was supported by the Fond for Science of the Republic of Serbia. Z.G.C.'s visit to the Robert Hill Laboratory was supported by the British Council and the University of Sheffield.