Elevated asymmetric dimethylarginine in young adult survivors of childhood acute lymphoblastic leukemia: A preliminary report

Background: Adult survivors of childhood malignancy are predisposed to late cardiovascular (CV) complications. Our aim was to estimate plasma levels of the endogenous nitric oxide formation inhibitor asymmetric dimethylarginine (ADMA), in long-term survivors of childhood acute lymphoblastic leukemia (ALL) treated with only chemotherapy. Methods: ADMA and its isomer symmetric dimethylarginine (SDMA) were measured in 25 former ALL patients (aged 18–28 years) who had survived without recurrent disease ≥ 5 years from completing chemotherapy without cranial irradiation, and in 20 healthy controls (aged 20–31 years). Results: Characteristics of the both groups were similar, except for lower high-density lipoproteins-cholesterol (HDL-C) in ALL survivors. Compared to controls, the former ALL patients exhibited significant, albeit small, rises in levels of ADMA (0.63 ± 0.09 [SD] vs. 0.57 ± 0.07 μmol/L; p = 0.016), but not SDMA, with a consequently increased ADMA to SDMA ratio (1.08 ± 0.22 vs. 0.91 ± 0.16; p = 0.004). The effect of former ALL on ADMA was attenuated (intergroup p = 0.10 [ANCOVA]) upon adjustment for HDL-C (ADMA vs. HDL-C regression coefficient: −0.065 ± 0.030 [SEM]; p = 0.03). Conclusions: ADMA is elevated in adult childhood ALL survivors, which can reflect late detrimental chemotherapy effects, partially related to minor lipid profile changes. Whether these subtle ADMA elevations might herald future CV morbidity, remains to be elucidated.     

Closely overlapping responses to tools and hands in left lateral occipitotemporal cortex

The perception of object-directed actions performed by either hands or tools recruits regions in left fronto-parietal cortex. Here, using functional MRI (fMRI), we tested whether the common role of hands and tools in object manipulation is also reflected in the distribution of response patterns to these categories in visual cortex. In two experiments we found that static pictures of hands and tools activated closely overlapping regions in left lateral occipitotemporal cortex (LOTC). Left LOTC responses to tools selectively overlapped with responses to hands but not with responses to whole bodies, nonhand body parts, other objects, or visual motion. Multivoxel pattern analysis in left LOTC indicated a high degree of similarity between response patterns to hands and tools but not between hands or tools and other body parts. Finally, functional connectivity analysis showed that the left LOTC hand/tool region was selectively connected, relative to neighboring body-, motion-, and object-responsive regions, with regions in left intraparietal sulcus and left premotor cortex that have previously been implicated in hand/tool action-related processing. Taken together, these results suggest that action-related object properties shared by hands and tools are reflected in the organization of high-order visual cortex. We propose that the functional organization of high-order visual cortex partly reflects the organization of downstream functional networks, such as the fronto-parietal action network, due to differences within visual cortex in the connectivity to these networks.     

Can clinical examination cause a Stener lesion in patients with skier's thumb?: A cadaveric study

Approximately one-third of all injuries of the upper limb and 7% of all injuries in skiing affect the ulnar collateral ligaments of the thumb metacarpophalangeal joint (skier's thumb). In some patients the collateral ligaments are displaced proximally over the adductor aponeurosis, resulting in a so-called Stener lesion. In these cases surgical treatment is indicated. We hypothesized that a Stener lesion could be provoked by clinical stability testing in patients with a skiers thumb and performed a cadaveric study on 10 Thiel fixated cadaver hands. For clinical stability testing, the thumb was manually deviated in radial direction in both 30° flexion and extension of the MP-joint. It was performed with maximum strength by two hand surgeons after sequential detachment of the ulnar collateral ligaments. After every sequence, it was assessed if the clinical stability testing had caused a Stener lesion. All of the 10 cadavers showed identical results while testing the clinical stability. A decreased stability was only found after cutting both parts of the ulnar collateral ligaments. A Stener lesion could not be provoked in any of the cadavers at any time by clinical stability testing. Summarizing our findings we conclude that a proper performed clinical stability testing of the thumb MP joint is a safe maneuver, which does not lead to a Stener lesion in patients with skier's thumb.     

Computer tomographic evaluation of talar edge configuration for osteochondral graft transplantation

To successfully surgically reconstruct osteochondral lesions of the talus, the exact three-dimensional (3D) configuration of the upper articular surface of the talus has to be respected. We assessed the talar geometry by measuring the coronal and sagittal talar edge radius and the frontal talar profile in multiplanar reconstructions of computer tomographic (CT) studies of 79 patients (83 feet) with a healthy ankle joint. An image visualization software designated for coordinate measurement was used to perform the measurement. In the coronal plane, the mean lateral talar edge radius was 4.0 mm and the medial 4.5 mm. In the sagittal planes the mean lateral talar edge radius was 20.3 mm, the radius of the sulcus 20.7 mm and the medial talar edge radius 20.4 mm. The talus showed a concave shape in coronal cuts. These results show a significant difference between medial and lateral talar edge configuration in coronal planes. The measurements of the lateral and medial sagittal radius and the mid-sagittal radius in the sulcus tali show no statistically significant difference. The depth of the talar sulcus shows no correlation to age or sex. Different sizes of custom-made tissue-engineered grafts according to the location of the osteochondral lesion at the talus are needed for exact surgical reconstruction of the anatomy. Osteochondral lesions are three dimensional; therefore, a 3D preoperative planning tool by CT scan or MRI is mandatory.     

Diversity of tailed phages in Baltic Sea sediment: large number of siphoviruses with extremely long tails

We present the first attempt at quantitative analysis of morphological diversity of tailed viruses obtained from marine sediments without ultracentrifugation or enrichment on specific host strains. Sandy mud samples were collected in the Gulf of Gdańsk in the spring, autumn and winter. VLPs were analyzed by transmission electron microscopy. The distribution of three groups of tailed phages was similar in all seasons (Siphoviridae: 52% on average; Myoviridae: 42%; Podoviridae: 6%). 19% of siphoviruses had prolate heads. Interestingly, 11% of siphoviral particles had tails longer than 300 nm, and 6% longer than 600 nm.     

Application of molecular techniques in the study of natural infection of Leishmania infantum vectors and utility of sandfly blood meal digestion for epidemiological surveys of leishmaniasis

Epidemiological studies on the distribution of leishmaniasis caused by Leishmania infantum Nicolle, 1908 (Kinetoplastida: Trypanosomatidae) have been based principally on serological surveys of the canine reservoir. This methodology is useful due to the facility of sampling, the rapidity in obtaining results, its consistency and because it allows the detection of heterogeneous foci of canine leishmaniasis (CanL) even in small areas. Other investigations have analysed Leishmania parasitism in sandflies (Diptera: Psychodidae: Phlebotominae) by using classical dissection techniques. These techniques allow the vector species to be incriminated in different foci, although they suffer from being very time consuming. Lately, studies in this field are increasingly using molecular techniques, which are faster and easier to perform. In the present work, we applied a nested-PCR in a study of natural infection of sandflies by Leishmania in three isolated farms where serological data on canine leishmaniasis of local dogs were also obtained. The analysis allowed the detection of 38.7% of females with positive nested-PCR (78%, 18% and 0%, respectively, in the different isolated farms). The positive Leishmania DNA samples were genotyped and identified as L. infantum. The results of this work provide new data for the vectorial capacity of Phlebotomus ariasi in a Pyrenean area, which can be considered at risk of becoming a new focus of CanL. The females with positive nested-PCR displayed blood in the midgut at different degrees of digestion, and/or were gravid. According to the multivariate logistic regression analysis, the risk of nested-PCR-positivity increased significantly with the degree of blood digestion (OR?=?1.3; P value?=?0.025). The Phlebotomus species and the presence of eggs were not statistically associated with nested-PCR positivity (P value of >0.05). The correlation of positive nested-PCR results with the presence of seropositive dogs in the farm confirms the utility of this technique in the study of the distribution and intensity of leishmaniasis foci. Also, the importance of sandfly blood-meal digestion for epidemiological surveys of leishmaniasis foci has been demonstrated.     

Evaluation of iron, vitamin B12 and folate intake in the selected group of women at childbearing age

The aim of this work was to evaluate iron, vitamin B12 and folate intake in the selected group of young females, aged 21-28 years. The study was carried out in winter 2008 with the use of 3-day dietary food records method. It has been shown too low mean iron (9.7 mg/d) and folate (270 microg/d) intake, on the level of 53% and 68% RDA respectively and also to high mean vitamin B12 (3.3 microg/d) intake (136% RDA). About 12% of questioned women took supplements, which supply additionally about 9.0 mg of iron, 192 microg of folate and near 1 microg of vitamin B12, what constitute together respectively 115, 127 and 199% RDA. Place of dwelling, BMI, smoking habits, physical activity have no influence an iron, vitamin B12 and folate intake.     

Nutritional value of daily food rations in 10 year old children with different body weight

The study objective was to assess the number and type of the daily consumed meals and to make a comparison between energetic and nutritional value in the meals consumed by children with normal and excessive body weight. A study was conducted in a group of 280 children aged 10 years (141 girls and 139 boys) in Bialystok. A 24 h dietary recall was taken of the day preceding the examination in order to perform a quantitative evaluation of daily food rations. Taking into consideration the particular meals, the energetic value and the content of basic dietary nutrients. Also cholesterol and fiber were evaluated, using the computer program Diet 2.0 developed in the Institute of Food and Nutrition in Warsaw. In the tested groups, a four-meal model predominated and the afternoon snack was most frequently missed. As many as 95% of children with normal body weight and 100% of children with excessive body weight admitted irregular eating between meals. The proportion in energy delivery from the respective meals was disturbed and nutritional abnormalities were found especially in the overweighted and obese children.     

Microcystin accumulation and antioxidant responses in the freshwater clam Diplodon chilensis patagonicus upon subchronic exposure to toxic Microcystis aeruginosa

We investigated the accumulation and toxicity of microcystin-LR (MCLR) in the digestive gland of the freshwater clam Diplodon chilensis patagonicus. Treated clams were fed with a toxic strain of Microcystis aeruginosa (NPJB1) during 6 weeks and control clams received the non-toxic strain NPDC1. Filtration rate was estimated for both groups. Toxic effects were evaluated through the hepatosomatic index (HSI) and different oxidative stress biomarkers, lipid peroxidation (content of thiobarbituric reactive substances-TBARS), protein oxidation (carbonyl groups) and reduced glutathione (GSH) levels, and enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). The extractable MCLR measured by ELISA in digestive gland extracts showed little or no change during the first 3 weeks and increased significantly at weeks 5 and 6. HSI was reduced by 30% in treated clams at weeks 5 and 6. No significant oxidative damage to lipids or proteins was. All the antioxidant defense parameters analyzed were significantly increased at week 5 or 6. GSH increased in treated clams at week 5, reaching 62% increase at week 6. SOD, CAT and GST activities were significantly increased in treated clams by 50%, 66% and 60%, respectively, at the end of the experiment. D. chilensis patagonicus can be exposed to prolonged cyanobacterial blooms accumulating significant quantities of MCLR, which could be a risk for mammals and birds, which feed on this species and, in a lesser extent, to humans.     

Derivatives of pyrrolo[3,4-d]pyridazinone, a new class of analgesic agents

A series of N2-{2-[4-aryl(benzyl)-1-piperazinyl(piperidinyl)]ethyl}pyrrolo[3,4-d]pyridazinones 4 and related derivatives 5 were synthesized as potential analgesic agents. The structures of the new compounds were elucidated by micro, spectral and X-ray analysis. Analgesic activity of the compounds was investigated in the phenylbenzoquinone induced ‘writhing’ and ‘hot plate’ test in mice and at radioligand binding assay. At ‘writhing’ test all compounds, without exception, were more active than acetylsalicylic acid (ASA) with ED₅₀ values ranging from 0.04 to 11 mg/kg (i.p.) (ED₅₀ for ASA - 39.15 mg/kg). Analgesic effect at the ‘hot plate’ test was observed for three compounds 4c,e,f at the dose 3-5 times higher then that of morphine (ED₅₀-3.39 mg/kg). At radioligand binding assay of 4c,e,f only compound 4f exhibited affinity for the μ-opioid receptors similar to that of Tramadol. The acute toxicity of the pyrrolopyridazinones 4, 5 were also studied and non toxic effect was observed at the 2000 mg/kg (5a 1420 mg/kg) i.p. dose level. On the basis of the available pharmacological data S-A relationship is discussed. The preferred conformational characteristic of 4, taken 4c as an example, was also described.