Human C3a and C3a desArg anaphylatoxins have conserved structures,in contrast to C5a and C5a desArg

Complement is a part of innate immunity that has a critical role in the protection against microbial infections, bridges the innate with the adaptive immunity and initiates inflammation. Activation of the complement, by specific recognition of molecular patterns presented by an activator, for example, a pathogen cell, in the classical and lectin pathways or spontaneously in the alternative pathway, leads to the opsonization of the activator and the production of pro‐inflammatory molecules such as the C3a anaphylatoxin. The biological function of this anaphylatoxin is regulated by carboxypeptidase B, a plasma protease that cleaves off the C‐terminal arginine yielding C3a desArg, an inactive form. While functional assays demonstrate strikingly different physiological effects between C3a and C3a desArg, no structural information is available on the possible conformational differences between the two proteins. Here, we report a novel and simple expression and purification protocol for recombinant human C3a and C3a desArg anaphylatoxins, as well as their crystal structures at 2.3 and 2.6 Å, respectively. Structural analysis revealed no significant conformational differences between the two anaphylatoxins in contrast to what has been reported for C5a and C5a desArg. We compare the structures of different anaphylatoxins and discuss the relevance of their observed conformations to complement activation and binding of the anaphylatoxins to their cognate receptors.     

Validation of the catalytic mechanism of Escherichia coli purine nucleoside phosphorylase by structural and kinetic studies

The catalytic mechanism of Escherichia coli purine nucleoside phosphorylase (PNP) is revised using site-directed mutagenesis, kinetic studies and structure determinations.The experimental evidence on the role of the particular catalytic amino acid during catalysis has not been available. Therefore, the active site mutants Arg24Ala, Asp204Ala, Asp204Asn, Arg217Ala and Asp204Ala/Arg217Ala were prepared and their kinetics and thermodynamic studies were carried out. The activity tests with natural substrates and 7-methylguanosine confirmed the earlier hypothesis, that catalysis involves protonation of the purine base at position N7 by Asp204, which is triggered by Arg217.The crystal structures of the wild type in complexes with phosphate and sulphate, respectively, and of the Arg24Ala mutant in complex with phosphate/sulphate were determined. The structural data show that previously observed conformational change is a result of the phosphate binding and its interaction with Arg24.As E. coli PNP is a promising candidate for the tumour-directed gene therapy, our results may also help to design efficient mutants useful in gene therapy.     

Coexistance of cerebral sinovenous thrombosis and Dandy Walker malformation in newborn

Cerebral sinovenous thrombosis in neonatal period may cause neurological impairment, epilepsy, and lead to stroke. It is caused primarily by coagulopathy of numerous reasons, occasionally perinatal asphyxia, traumatic delivery and hyperhomocysteinemia. Dandy-Walker malformation is characterized by agenesis or hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle, and enlargement of the posterior fossa. Dandy-Walker malformation, variant, and mega cisterna magna represent a spectrum of developmental anomalies. Insults to developing cerebellar hemispheres and the fourth ventricle are believed to be the cause of malformation. Our patient was born from noncomplicated pregnancy, noncomplicated nontraumatic vaginal delivery at term, excellent Apgar scores, without peculiarities in clinical status. She was brest-fed by the 42nd hour of life when she had rightsided seizures during sleep that repeated for five times in next 24 hours. Brain Ultrasound (US) revealed clot in left lateral ventricle, slight dilatation of left ventricle, both sided periventricular echodensity, ischemia, slight enlargement of forth ventricle and a bit smaller cerebellum. There was no visible flow through left transverse, superior sagittal and straight sinus. Magnetic Resonance (MRI) confirmed the finding and showed thrombosis of left and right transverse venous sinuses and confluence of sinuses. Electroencephalogram (EEG) showed leftsided focal changes. The newborn was treated with phenobarbiton for 8 days and had no convulsions during that period. All coagulation parameters, homocistein, lipoproteins (a) and D-dimers were normal. There were no mutations on FV R506Q, PT 20210A, MTHFR 677C/T. No antiphospholipides were found. Heart US showed no structural anomalies. No other patology or risk factors were present at the time. Before discharge, US showed hydrocephalus. Flow in affected sinuses was visible with color Doppler. MRI showed recanalization of affected sinuses, also hydrocephalus and presentation of Dandy Walker On EEG there was borderline finding. Due to progression of hydrocephalus ventriculo-peritoneal shunt was placed. In age of 1 year EEG was slower for age but without focus. Neurological development was normal for age. The question is whether this child had intrauterine insult and inception of Dandy Walker with further postnatal progress of thrombosis and evolution to full picture of Dandy Walker with hydrocephalus OR thrombosis that led to development of hydrocephalus and Dandy Walker malformation in this child were accidental coexistance.     

Differential diagnostic relevance of high resolution magnetic resonance in patients with possible multiple system atrophy (MSA) - A case report

Multiple system atrophy (MSA) is sporadic, progressive neurodegenerative disorder characterized clinically by autonomic dysfunction, Parkinsonism (MSA-P), and cerebellar ataxia (MSA-C) in any combination. Parkinsonism is present in the majority of patients (80%). Early in the course of the disease autonomic dysfunctions are present in approximately 40% of patients, while the domination of cerebellar symptoms is present in 20% of all patients. According to second consensus statement on diagnosis of MSA, to make the diagnosis of possible MSA, except Parkinsonism or a cerebellar syndrome, there must be one feature involving autonomic dysfunction plus one other additional that can include findings on history, clinical examination or changes in structural or functional imaging. We present a case of 60-year old male with Parkinsonism and cerebellar symptoms accompanied with signs of autonomic nervous system involvement. Level of autonomic dysfunction was not the level required for the diagnosis of probable MSA. On initially performed 1.5T MRI, the most prominent neurodegenerative feature of brain stem, cerebellum and basal ganglia was atrophy, however features like "hot-cross bun" sign, "slit-like" putaminal rim and middle cerebellar peduncle hyperintensities were detected only after MR imaging on higher resolution (3T) device. Our case points to the possibility that some typical structural changes that can help in diagnostic process may not be clearly visible on 1.5 T MRI devices. In such cases we suggest using 3T MRI device, if feasible, in order to demonstrate findings that may help in establishing the diagnosis of possible MSA.     

Dilemma of antiepileptic drugs withdrawal in symptomatic epilepsy

A successful treatment of epilepsy depends on numerous factors such as etiology, genetics and environmental impact. An exact diagnosis, treatment and an adequate selection of antiepileptic drugs (AED) are important from the very beginning. The patient with symptomatic epilepsy caused by the brain tumor (low-grade astrocytoma in the left parietal lobe, surgically removed 17 years after the first manifestation of illness) is presented in this study. He has been seizure free for 6 years. The represented case study deals with the risk-benefit analysis of the discontinuation of the prescribed antiepileptic treatment that has lasted for 23 years.     

Fragile X-premutation tremor/ataxia syndrome (FXTAS) in a young woman: clinical, genetics, MRI and 1H-MR spectroscopy correlates

It is generally thought that fragile X-associated tremor/ataxia syndrome (FXTAS) represents a late-onset neurodegenerative disorder occuring in male carriers of a premutation expansion (55-200 CGG repeats) in the fragile X mental retardation 1 (FMR 1) gene. However, several female patients with FXTAS have also been reported recently. Here, we describe a 23-year old woman with positive family history of mental retardation and autism who presented clinically with action tremor, ataxia, emotional disturbances and cognitive dysfunction. Magnetic resonance imaging (MRI) of the brain showed diffuse cortical atrophy, while 1H-MR spectroscopy (MRS) revealed decreased levels of N-acetylaspartate (NAA) in the cerebellum, basal ganglia, and pons. Genetic testing confirmed heterozygous FMR 1 gene premutation of 100 CGG repeats in the abnormal allele and 29 CGG repeats in the normal allele. We concluded that FXTAS may be an under-recognized disorder, particularly in women.     

Angiomyoma--angioleiomyoma of the cheek

The authors present the case of an angiomyoma--angioleiomyoma of the cheek in a 58-year-old man. The tumour was palpable, although clinically not visible, and the only case of a tumour of smooth muscle treated in the Clinical Department of Oral Surgery over the last 40 years. The operation was performed in the Outpatient Department by intraoral procedure. The postoperative course passed without complications. Current literature on leiomyomas is cited in the Introduction, followed by presentation of the case and histological characteristics of the tumour The example is presented as a rarity and one of the differential diagnostic possibilities in the diagnostics of soft tissue tumours in the oral cavity.     

Efficacy and safety of inferior turbinate coblation-channeling in the treatment of nasal obstructions

The aim of this study was to evaluate the safety and effectiveness of coblation-channeling in the treatment of inferior turbinate hypertrophy. The study was conducted in the Department of ENT Head and Neck Surgery, Split University Hospital Center, Split, Croatia. Fifty-two patients with inferior turbinate hypertrophy who were refractory to medical therapy were evaluated for coblation. The procedures were performed under local anesthesia using an ArthroCare ReFlexUltra 45 wand; three submucosal channels were made per turbinate. Clinical examinations, a questionnaire on individual nasal symptoms (hyposmia, nasal drainage and post-nasal drip), a 10-cm visual analog scale (VAS) grading general nasal obstructions, and rhinomanometry before and 8 weeks after the treatment were administered to assess treatment outcomes. No adverse effects were encountered. Nasal breathing was significantly improved in all patients, decreasing the VAS from a median of 7 (range 2-9) to 1 (range 0-3) (p < 0.001). Total nasal resistance decreased from 0.44 Pa +/- 0.50 to 0.24 Pa +/- 0.11 (p = 0.005). Improvement was statistically significant for all three symptoms (hyposmia [p = 0.005], nasal drainage [p = 0.003] and post-nasal drip [p < 0.001]). In this paper, we demonstrate that coblation-channeling of the hypertrophic inferior turbinate is an effective and safe way to reduce nasal obstruction symptoms.     

Impact of body composition on performance in fitness tests among personnel of the Croatian navy

The purpose of this study was to determine the impact of body weight on fitness tests among the personnel of the Croatian navy. Forty two naval personnel (age 27 +/- 4.1 years; body mass 86.2 +/- 4.9 kg; height 184.6 +/- 7.4 cm; body fat percentage 17.3 +/- 5.2) participated in this study. In order to evaluate the fitness of the naval servicemen, we applied a testing procedure that included measurements of 7 fitness tests and 15 body anthropometric tests. A negative correlation was found between the body fat percentage and all the analyzed sprint tests and three anaerobic power tests (r), SP5 (r = -0.42), SP10 (r = -0.51), SP20 (r = -0.53), SJ (r = -0.45), CM (r = -0.57), SLJ (r = -0.67). Also a negative correlation was found between the body fat percentage and VO2(max) (r = -0.44). A positive correlation was found between the sprint test and the power performance test and thigh and calf girth. Spiriting ability is influenced by the strength of a person. This is one of the reasons why we found a positive correlation between the sprint test (SP5, SP10 and SP20) and thigh and calf girth. In this study we found a negative correlation between body fat percentages and all the sprint tests and three anaerobic power tests and VO2(max). The ectomorph somatotypes have positive correlations with all variables. The mesomorph somatotypes have the greatest positive correlations with all variables. The endomorph somatotypes have negative correlations with all variables. According to the body composition of Croatian naval servicemen we can conclude that they need a sufficient level of strength and endurance for everyday tasks. The effectiveness of a weight-management program is determined by the success of the participants in losing the necessary amount of weight and being able to maintain that weight loss. This requires long-term tracking of these individuals in a naval environment.     

Frequency and Incidence of Pyrenochaeta terrestris in Root Internodes of Different Maize Hybrids

The frequency and incidence of Pyrenochaeta terrestris and symptom type on the roots of each internode of four maize hybrids of different maturity groups were studied 70 days after sowing. The fungus developed in the roots of all developed internodes (from the primary to the sixth or seventh internodes of all tested hybrids). The average frequency and incidence of P. terrestris in the roots of late and medium early maturity hybrids ranged from 29.5 to 55.2% and from 11.8 to 22.7%, respectively. The highest frequency of the fungus was at the 2nd root internode (93.3%), and its greatest incidence was detected in the mesocotyl of the medium early hybrid H‐1 (56.9%). Necrosis predominated in the roots of the medium early (i.e. medium late maturity hybrids, 44.5% and 44.3%, respectively), whereas reddish pink symptoms were recorded in the roots of the late hybrids (51% and 42.5%). Because the fungus always produces a distinctive red pigment on carnation leaf agar (CLA) in a light regime, these conditions can be recommended for the reliable identification of P. terrestris, even if pycnidia are not formed. These are the first reports of the successive distribution of the fungus in each maize root internode of different hybrids, as well as the use of CLA medium in the identification of the P. terrestris.