Obesity is associated with increased level of kisspeptin in mothers' blood and umbilical cord blood - a pilot study.

OBJECTIVE: Kisspeptin (KP) is a major regulator of reproductive functions. It has also been shown to be involved in the metabolic changes associated with obesity. According to the well-established concept of prenatal programming, environmental factors can influence physiological and behavioral systems at the early stages of development. Thus, we hypothesized that in pregnant women, obesity can be associated with alterations in the levels of KP. We also assumed that the observed changes in obese mothers' blood (MB) would be reflected in the umbilical cord blood (CB). MATERIALS AND METHODS: We collected MB and CB from obese and nonobese women and analyzed the differences in metabolic and hormonal profiles, including KP concentration, using commercially available assays. RESULTS: We found that the level of KP was increased in the MB and CB of obese patients compared to nonobese subjects (p<0.05). A strong correlation was observed between the concentration of KP in MB and CB (r=0.8343; p<0.01). Moreover, we detected that the differences in the adipokine profile observed in the MB were not reflected in CB. CONCLUSIONS: Our results indicate that blood KP concentration can serve as a valuable marker in pregnant women. However, further studies are needed to understand the alterations of this peptide in obese pregnant woman and their potential effects on offspring.

Role of hepcidin in physiology and pathophysiology. Emerging experimental and clinical evidence.

Normal iron metabolism is an inherent feature of maintaining homeostasis. There is a wide range of iron disorders, which arise from iron deficiency or overload. In addition, disturbances in iron metabolism are observed in the course of numerous chronic diseases. Since iron is an essential constituent of hemoglobin, different types of anemia are clinical manifestations of both iron deficit or excess. This seemingly contradictory statement may be elucidated by the presence of hepcidin. Hepcidin is a primary regulator of iron metabolism in the human body. By promoting ferroportin degradation, hepcidin decreases the amount of iron in the circulation due to iron sequestration in the tissues and reduced intestinal absorption. Altered hepcidin concentration is a compensatory mechanism aimed at restoring iron homeostasis in various physiologic states, including pregnancy. However, hepcidin may also participate in the pathophysiologic background of hereditary hemochromatosis, anemia of chronic disease, myelodysplastic syndromes or ß-thalassemia. Moreover, hepcidin is an acute-phase protein involved in innate immunity reactions. In our paper, we provide a comprehensive review of the physiologic and pathophysiologic functions of hepcidin. We present current knowledge on the structure, physiologic role and its expression control, as well as demonstrate the contribution of hepcidin in a state of illness. We also summarize the significance of hepcidin in normal and complicated pregnancy. Emphasizing the alterations in hepcidin upon treatment of specific diseases and their position in certain pathomechanisms, we support clinicians with practical aspects related to hepcidin.

Serum levels of spexin and kisspeptin negatively correlate with obesity and insulin resistance in women.

Spexin (SPX) and kisspeptin (KISS) are novel peptides relevant in the context of regulation of metabolism, food intake, puberty and reproduction. Here, we studied changes of serum SPX and KISS levels in female non-obese volunteers (BMI<25 kg/m(2)) and obese patients (BMI>35 kg/m(2)). Correlations between SPX or KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, ghrelin and GLP-1 were assessed. Obese patients had lower SPX and KISS levels as compared to non-obese volunteers (SPX: 4.48+/-0.19 ng/ml vs. 6.63+/-0.29 ng/ml; p<0.001, KISS: 1.357+/-0.15 nmol/l vs. 2.165+/-0.174 nmol/l; p<0.01). SPX negatively correlated with BMI, HOMA-IR, insulin, glucagon, active ghrelin and leptin. Positive correlations were found between SPX and QUICKI index, McAuley index, serum levels of obestatin, GLP-1 and adiponectin and orexin-A Serum KISS negatively correlated with BMI, HOMA-IR, serum levels of insulin, glucagon, active ghrelin and leptin. KISS positively correlated with QUICKI index, McAuley index and adiponectin. In summary, SPX and KISS show negative correlations with obesity, insulin resistance indices, and hormones known to affect insulin sensitivity in females. Both, SPX and KISS could be therefore relevant in the pathophysiology of obesity and insulin resistance.

Plasma ghrelin and interleukin-6 levels correlate with body mass index and arterial blood pressure in males with essential hypertension.

We examined an association between ghrelin, including its major isoforms, interleukin-6 (IL-6), body mass index (BMI), and mean arterial pressure (MAP) in male overweight patients with essential hypertension. Twenty hypertensive male patients with newly diagnosed essential hypertension (EH) before starting drug treatment and 22 age-matched healthy controls were enrolled in the study. Fasting total plasma ghrelin (TGhr), acyl ghrelin (AGhr), des-acyl ghrelin (DGhr) and IL-6 were determined and correlations between studied parameters were calculated. We found significantly lower total plasma ghrelin and higher plasma IL-6 in hypertensives when compared with the control. In patients with hypertension the negative correlations were found: between TGhr and BMI, DGhr and BMI, TGhr and MAP, and between DGhr and MAP. IL-6 positively correlated with BMI and MAP in hypertensive subjects. No correlations between all forms of ghrelin and IL-6 were noted. The changes in plasma ghrelin and IL-6 contribute independently to the elevated blood pressure in essential hypertension. Negative correlation of DGhr and MAP may suggest its hemodynamic involvement in regulation of blood pressure.

Development of heterotopic ossifications, blood markers and outcome after radiation therapy in spinal cord injured patients.

STUDY DESIGN: Retrospective study. OBJECTIVES: This study was implemented to detect risk factors for the developing of heterotopic ossifications (HOs) in spinal cord injury (SCI) patients. SETTING: This study was conducted in Murnau, Germany. METHODS: All patients from 2008-2012 with acute SCI were routinely examined by ultrasound of the hips every 2 weeks. The sub group of SCI patients suffering of HO of the hips were extracted and the incidence of developing an HO was calculated. Parameters like age, level of injury, ASIA Impairment Scale (AIS), duration time of accident until diagnosis of HO, Brooker stage, localization of HO (magnetic resonance imaging (MRI)) and symptoms like thrombosis, emboli, decrease of range of motion (ROM), dermal symptoms, swelling, increase in D-Dimere level, were evaluated. Also accompanying injuries of the brain, lung and extremities were recorded. RESULTS: From January 2008 until January 2012, 575 patients with an acute and traumatic SCI were treated in our Department. During this period 32 HOs were detected in the muscles surrounding the hip. In 10 cases a single side and in 22 cases both sides were affected. A total of 26 patients were detected showing up a Brooker 0, two patients Brooker 1, and five patients a Brooker stage >2. The adductor muscles showed an edema in 19 cases and the quadriceps muscles were affected in 15 cases. 26% of all SCI patients showed AIS A status, but in patients who developed HO, 64% have had an AIS A status. 19% of patients with a HO were AIS B and 9.5% showed an AIS C and D. Regarding the level of injury the distribution of patients suffering of HO was comparable to the distribution of SCI patients without HO. In mean HO were detected 9 weeks after SCI and no new HO were found after the 22nd (n=1) week of injury. Clinical symptoms such as swelling, pain, redness or decrease in ROM or increase in D-Dimere levels were seen in 24 cases. Accompanying injuries like brain injury and lung contusions were found in 83% of patients developing HO. The incidence of thrombosis was comparable to SCI patients without HO. One patient with no accompanying injuries or clinical symptoms was detected by routinely performed ultrasound. CONCLUSIONS: The risk of developing HO in patients with traumatic SCI is 5.5% but increases when accompanying injuries of the brain and lung occur. Patients with a neurological status of AIS A must also be quoted as risk patients. When considering the described risk factors and clinical symptoms, 96% of all HO can be detected.

Evaluation of an aSi-EPID with flattening filter free beams: applicability to the GLAaS algorithm for portal dosimetry and first experience for pretreatment QA of RapidArc.

PURPOSE: To demonstrate the feasibility of portal dosimetry with an amorphous silicon mega voltage imager for flattening filter free (FFF) photon beams by means of the GLAaS methodology and to validate it for pretreatment quality assurance of volumetric modulated arc therapy (RapidArc). METHODS: The GLAaS algorithm, developed for flattened beams, was applied to FFF beams of nominal energy of 6 and 10 MV generated by a Varian TrueBeam (TB). The amorphous silicon electronic portal imager [named mega voltage imager (MVI) on TB] was used to generate integrated images that were converted into matrices of absorbed dose to water. To enable GLAaS use under the increased dose-per-pulse and dose-rate conditions of the FFF beams, new operational source-detector-distance (SDD) was identified to solve detector saturation issues. Empirical corrections were defined to account for the shape of the profiles of the FFF beams to expand the original methodology of beam profile and arm backscattering correction. GLAaS for FFF beams was validated on pretreatment verification of RapidArc plans for three different TB linacs. In addition, the first pretreatment results from clinical experience on 74 arcs were reported in terms of γ analysis. RESULTS: MVI saturates at 100 cm SDD for FFF beams but this can be avoided if images are acquired at 150 cm for all nominal dose rates of FFF beams. Rotational stability of the gantry-imager system was tested and resulted in a minimal apparent imager displacement during rotation of 0.2 ± 0.2 mm at SDD = 150 cm. The accuracy of this approach was tested with three different Varian TrueBeam linacs from different institutes. Data were stratified per energy and machine and showed no dependence with beam quality and MLC model. The results from clinical pretreatment quality assurance, provided a gamma agreement index (GAI) in the field area for six and ten FFF beams of (99.8 ± 0.3)% and (99.5 ± 0.6)% with distance to agreement and dose difference criteria set to 3 mm/3% with 2 mm/2% thresholds, GAI resulted (95.7.0 ± 2.3)% and (97.2 ± 2.1)%. CONCLUSIONS: The GLAaS methodology, introduced in clinical practice for conventional flattened photon beams for machine, IMRT, and RapidArc quality assurance, was successfully adapted for FFF beams of Varian TrueBeam Linac. The detector saturation effects could be eliminated if the portal images acquired at 150 cm for all nominal dose rates of FFF beams.

Common knowledge of leukemia among the youth and their attitude to the diagnosed disease.

PURPOSE: The aim of the study is to evaluate common knowledge shared by leukemia patients aged 12-18 yrs. and to determine their attitude to the diagnosed disease. MATERIAL AND METHOD: The study group consisted 30 of youth aged 12-18 yrs with diagnosed leukemia, which expressed agreement on participation in investigation. The study employed an own questionnaire entitled: "Common Knowledge of Leukemia among Youth and Their Attitudes to the Diagnosed Disease". RESULTS: Results passed of investigations one surrendered to analysis and one introduced inform of diagrams. Talked over results of investigations summed up are discussion and conclusions. Discussion achieves results of own investigations to these passed by Binnbesela's and of relating current knowledge about new-coined word disease among young people from 12 to 18 year of life, contains also considerations relating situation in which one is found young people with recognized leukemia. CONCLUSIONS: The level of knowledge about leukemia in 12-18-year-old patients is highest in 18-year-old respondents. There is no dependence between the time lapse from the moment of diagnosis and the increase of knowledge on the subject. The attitude of young leukemia patients to their own disease does not change with the time lapse from the moment of diagnosis.

Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia.

Tardive dyskinesia (TD) is a common side effect of long-term medication with typical neuroleptics. TD presents itself by abnormal involuntary movements and may lead to a potentially disabling and chronic clinical course. A vast majority of patients suffering from schizophrenia are smokers. Smoking has been reported to induce the activity of the CYP1A2 enzyme, which is an established metabolic pathway within the disposition of antipsychotics. Recently, a C-->A genetic polymorphism in the first intron of the CYP1A2 gene was reported to influence CYP1A2 activity in smokers. Subsequently, a pharmacogenetic study in 85 U.S. patients with schizophrenia (44 smokers, 41 individuals with unknown smoking status) showed the C/C genotype to be associated with higher TD severity (measured by the Abnormal Involuntary Movement Scale, AIMS) than the A/C or A/A genotype. This finding prompted us to investigate whether this effect was also present in a larger German sample of 119 patients with schizophrenia (82 smokers, 37 individuals with unknown smoking status). However, we could not replicate the reported association. The median AIMS scores did not differ between individuals with the A/A, A/C, or C/C genotypes. In an additional analysis, we compared the genotypic and allelic distribution among individuals grouped according to the criteria established by Schooler and Kane [1982: Arch Gen Psychiatry 39:486-487] (persistent TD vs. absent TD). We did not observe a differential genotypic or allelic distribution between the two diagnostic groups. Thus, our results do not support the hypothesis that the C-->A polymorphism in the CYP1A2 gene is involved in the etiology of TD in the German population.

Sequencing and linkage analysis of a Coxiella burnetii 2.1 kb NotI fragment.

Most of the Coxiella burnetii isolates (72 of 80) available in our institute share a 2.1 kb NotI fragment. Sequence analysis revealed two incomplete open reading frames (ORF) for putative genes hemA and bcR coding for glutamyl-tRNA-reductase and bicyclomycin resistance protein, respectively. Upon completing the ORF for the hemA gene by sequencing the adjacent NotI/EcoRI fragment a third ORF for the putative prfA gene was determined coding for release factor 1, an enzyme catalysing the last step in protein biosynthesis.

Analysis of the entire nucleotide sequence of the cryptic plasmid QpH1 from Coxiella burnetti.

The complete plasmid QpH1 from Coxiella burnetti, isolate 'Nine Mile', phase I, was cloned as NotI fragment with a size of 37329 bp. The entire plasmid was sequenced by the chain termination method after EcoRI subcloning. 37 open reading frames coding for polypeptides larger than 100 amino acid residues were determined. The predicted polypeptide products of the open reading frames were compared by computer analysis with reported protein sequences. Homologies of predicted polypeptide products to analogous proteins are described.

Monoclonal antibody based capture ELISA/ELIFA for detection of Coxiella burnetii in clinical specimens.

A CAPTURE ELISA/ELIFA system based on monoclonal capture and biotinylated monoclonal detection antibody is described. The assay is fast, highly specific and detects a minimum dose of 2500 Coxiella (C.) burnetii particles. In contrast to the sophisticated and cumbersome isolation procedures, even non-specialized laboratories could use this assay system for investigating clinical samples of different origin for C. burnetii within a short period of time.

Concomitant lymphangioma and arteriovenous malformation of the orbit.

An 8-year-old girl had an orbital-adnexal lymphangioma and ipsilateral orbital and middle cranial fossa arteriovenous malformations. High-resolution magnetic resonance image scanning, orbital ultrasonography, and digital subtraction angiography were used for diagnosis and preoperative assessment. Complications related to this vascular neoplasm included amblyopia, acute hemorrhage with proptosis, exposure keratitis, cosmetic deformity, and recurrent preseptal cellulitis. The girl was treated with both embolization and orbital surgery for recurrent hemorrhage and proptosis. We postulated that the coexistence of a lymphangioma and arteriovenous malformation represents an unusual and extensive maldevelopment of vascular embryogenesis.

Detection of Coxiella burnetii by the immunoperoxidase technique.

An immunoperoxidase method using Coxiella (C.) burnetii-specific hyperimmune serum raised in rabbits, and swine anti-rabbit horseradish peroxidase conjugate was applied to visualize C. burnetii in BGM cell cultures. The technique proved to be highly specific and did not result in any unspecific background staining. The technique was applied successfully to study the organism during multiplication in vacuoles of epithelial cells and in the phagolysosomes of macrophages. Preliminary results further indicate that the technique may be useful for the detection of the pathogen in tissues and milk samples.

Intrapapillary refractile bodies in optic nerve sheath meningioma.

Intrapapillary refractile bodies were observed in seven of 13 patients with chronic optic disc edema secondary to optic nerve sheath meningioma. The observation of refractile bodies preceded or coincided with decline in vision and disappeared as optic atrophy supervened. Intrapapillary refractile bodies appear to be a nonspecific sign of chronic optic disc edema.

Optic nerve sheath meningiomas. Clinical manifestations.

A retrospective clinical study of optic nerve sheath meningiomas based on 22 patients showed that symptoms most commonly develop in women between the ages of 35 and 60 years. The most common presenting symptoms were decreased vision and transient visual obscurations. In the earliest stages, many patients presented with normal to mildly impaired acuity (despite subjectively decreased vision), optic disc edema and enlargement of the blind spot. Optic disc edema was frequently associated with refractile bodies indicative of chronic swelling. Optic disc edema preceded the development of optic atrophy. Another group of patients presented with a history of longstanding vision loss, visual acuity of 20/200 or worse and optic atrophy. Optociliary shunt vessels were late findings only seen in five patients. The most consistent visual field abnormality was peripheral constriction. Cecocentral scotomas were uncommon. Intracranial involvement was present in five patients. There were two patients with bilateral optic nerve sheath meningiomas without CT evidence of intracranial involvement. Computerized tomography was found to be indispensable in the diagnosis of optic nerve sheath meningiomas and the detection of intracranial involvement.

Effect of certain factors modifying the lipid-mobilizing activity in vitro in the serum of rats during hypothermia.

The serum of hypothermic animals shows in vitro the ability of mobilizing fatty acids from the adipose tissue. This ability is quantitatively comparable to the lipolytic activity of glucagon but is lower than that of adrenaline. Propranolol decreases the lipid-mobilizing activity in the serum of hypothermic animals in vitro. Similarly insulin added to the medium with the serum of hypothermic animals decreased the lipid-mobilizing activity.

Somatostatin effect on the level of adenyl nucleotides in the blood and tissues of rats during short-lasting hypothermia.

Short-lasting hypothermia during thiobutabarbital general anaesthesia causes no decrease of the absolute ATP level in the blood and liver of rats. The adenylate energy charge in the tissues is relatively high - 0.86 in the liver and 0.85 in the muscles, which might be an evidence of a significant "energy sparing" during moderate hypothermia (26 +/- 1 degree C). Somatostatin in a dose of 20 micrograms/kg of body weight given to the rats during hypothermia decreased the ATP level, the ATP/ADP ratio and the adenylate energy charge in the studied tissues, especially in the liver, evidencing increased intensity of catabolic processes caused by the inhibitory action of somatostatin on the release of insulin and glucagon, among other hormones, and on the change of the insulin/glucagon ratio.