THE EFFECT OF THERAPY WITH INSULIN ANALOGUES (ASPART AND GLARGINE) ON OXIDATIVE STRESS PARAMETERS IN PATIENTS WITH TYPE 1 DIABETES MELLITUS.

Context: There are evidences that excessive production of reactive oxygen species is one of important abnormalities that contribute to development of chronic diabetic complications. Objective: To test the effect of intensive insulin therapy with analogues through the examining the level of oxidative stress parameters. Subjects and Methods: Comparison of data obtained by prospective analysis in 49 patients with T1DM was used, before and after six months of intensive insulin analog therapy. Results: The values of all three investigated parameters of oxidative stress malondialdehyde (MDA); xanthine oxidase (XO) and nitrates and nitrites (NOx) in our population with T1DM compared to the control (group of 42 voluntary blood donors) are statistically higher. The levels of antioxidant protection parameters compared to the control group also differ; the activities of catalase and glutathione peroxidase (GPx) are statistically higher in our population of T1DM patients compared to the control and superoxide dismutase (SOD) activities are statistically lower.The values of all three examined parameters of oxidative stress decrease after six months of intensive insulin analog therapy and were statistically lower after the therapy: for MDA p<0.001, for XO p<0.01 and for NOx p<0.05. The activities of catalase (p<0.001) and GPx (p<0.01) both decrease with therapy, while the activity of SOD is highest after the sixth month of therapy (p<0.001). Conclusion: In our patients with T1DM compared to the control the level of oxidative stress is significantly higher. Intensive insulin analog therapy with aspart and glargine promotes predominantly the improvement of oxidative stress, and in a less degree antioxidant protection.

Current progress in the therapeutic options for mitochondrial disorders.

Mitochondrial disorders manifest enormous genetic and clinical heterogeneity - they can appear at any age, present with various phenotypes affecting any organ, and display any mode of inheritance. What mitochondrial diseases do have in common, is impairment of respiratory chain activity, which is responsible for more than 90% of energy production within cells. While diagnostics of mitochondrial disorders has been accelerated by introducing Next-Generation Sequencing techniques in recent years, the treatment options are still very limited. For many patients only a supportive or symptomatic therapy is available at the moment. However, decades of basic and preclinical research have uncovered potential target points and numerous compounds or interventions are now subjects of clinical trials. In this review, we focus on current and emerging therapeutic approaches towards the treatment of mitochondrial disorders. We focus on small compounds, metabolic interference, such as endurance training or ketogenic diet and also on genomic approaches.

[Multiple well demarcated skin erosions and ulcers following exanthematous drug eruption after sultamicillin therapy]. / Scharfrandige Erosionen und Ulzerationen im Anschluss an ein Arzneimittelexanthem nach Sultamicillin-Gabe.

This article presents the case of a patient with newly developed skin erosions and ulcerations following an exanthematous drug eruption due to sultamicillin therapy. The skin lesions were treated topically with clobetasol and prednicarbate and orally with methylprednisolone. A skin smear revealed massive growth of Escherichia coli bacteria. Blood cultures were negative. The cause for developing ecthyma gangrenosum in our patient were iatrogenic immunosuppression and transient bacteremia.

The effect of subchronic supplementation with folic acid and l-arginine on homocysteine-induced seizures.

The aim of the present study was to examine the effect of subchronic co-administration of folic acid (F) and l-arginine (A) on behavioural and electroencephalographic (EEG) characteristics of dl homocysteine thiolactone (H) induced seizures in adult rats. The activity of membrane ATPases in different brain regions were also investigated. Rats were treated with F, A, or vehicle for 15 days (regimen: F 5 mg/kg + A 500 mg/kg (F5A500); F 10 mg/kg + A 300 mg/kg (F10A300)). Seizures were elicited by convulsive dose of H (H, F5A500H, F10A300H) Subchronic supplementation with F and A did not affect seizure incidence, number of seizure episodes, and severity in F5A500H and F10A300H groups vs. H group. However, a tendency to increase latency and decrease the number of seizure episodes was noticed in the F10A300H group. EEG mean spectral power densities during ictal periods were significantly lower in F10A300H vs. H group. The activity of Na+/K+-ATPase and Mg2+-ATPase was significantly increased in almost all examined structures in rats treated with F and A. We can conclude that subchronic supplementation with folic acid and l-arginine has an antiepileptic effect in dl homocysteine thiolactone induced epilepsy.

The Influence of Finasteride on Mean and Relative Spectral Density of EEG Bands in Rat Model of Thioacetamide-Induced Hepatic Encephalopathy.

Liver failure is associated with a neuropsychiatric syndrome, known as hepatic encephalopathy (HE). Finasteride, inhibitor of neurosteroid synthesis, may improve the course of HE. The aim of our study was to investigate the influence of finasteride on mean and relative power density of EEG bands, determined by spectral analysis, in rat model of thioacetamide-induced HE. Male Wistar rats were divided into groups: (1) control; (2) thioacetamide-treated group, TAA (900 mg/kg); (3) finasteride-treated group, FIN (150 mg/kg); and (4) group treated with finasteride (150 mg/kg) and thioacetamide (900 mg/kg), FIN + TAA. Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered during 3 subsequent days, and in FIN + TAA group FIN was administered 2 h before every dose of TAA. EEG was recorded 22-24 h after treatment and analyzed by fast Fourier transformation. While TAA did not induce significant changes in the beta band, mean and relative power in this band were significantly higher in FIN + TAA versus control group (p < 0.01). TAA caused a significant decline in mean power in alpha, theta, and delta band, and in FIN + TAA group the mean power in these bands was significantly higher compared with control. While in TAA group relative power was significantly decreased in theta (p < 0.01) and increased in delta band (p < 0.01) versus control, the opposite changes were found in FIN + TAA group: an increase in theta (p < 0.01) and a decrease in delta relative power (p < 0.01). In this study, finasteride pretreatment caused EEG changes that correspond to mild TAA-induced HE.

Clinical scores for the prediction of esophageal varices in patients with liver cirrhosis.

INTRODUCTION: Esophageal bleeding is one of the most important and dramatic complications of liver cirrhosis in our everyday practice. Considering the costs of repeated upper endoscopy (UE) there is an increasing number of studies focusing on noninvasive para-meters for the assessment of esophageal varices (EV). PATIENTS AND METHODS: Retrospective study included 74 patients with alcoholic and viral liver cirrhosis treated at Clinic of Gastroenterology and Hepatology, Clinical Center of Serbia. The data were obtained from patients medical records including history, biochemical, ultrasonography and UE findings. RESULTS: The average value of the RLLD/INR for patients who showed evidence of EV during UE and in those who didn't was 10.46 ±â€ˆ3.09 and 12.24 ±â€ˆ3.43, respectively (p = 0.019, p < 0.05). Cutoff value (11.5) of RLLD/INR showed a sensitivity of 64.15% and specificity of 66.67% (1.92LR+, and 0.54 LR-, AUROC 0.639) for the detection of EV. The average value of PC/SBD for patients who showed evidence of EV during UE and in those who didn't was 619.79 ±â€ˆ492.96 and 1423.1 ±â€ˆ908.2, respectively (p = 0.0, p < 0.05). The average value of RLLD/SA was 5.5 ±â€ˆ0.17 and 4.57 ±â€ˆ0.17 (p = 0.015, p < 0.05) for patients who showed evidence of EV -during UE and in those who didn't, respectively. CONCLUSION: Noninvasive assessment of EV using scores based on ultrasonography and laboratory is simple, inexpensive, and could be a useful tool in limiting the number of repeated UE.

The effect of subchronic supplementation with folic acid on homocysteine induced seizures.

Influence of folic acid on the CNS is still unclear. Folate has a neuroprotective effect, while on the other hand excess folate can exacerbate seizures in epileptics. The aim of the present study was to examine the effect of subchronic administration of folic acid on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone induced seizures in adult rats. The activity of Na⁺/K⁺-ATPase and Mg²âº-ATPase in different brain regions was investigated. Adult male Wistar rats were divided into groups: 1. Controls (C, 0.9% NaCl); 2. DL homocysteine-thiolactone 8.0 mmol/kg (H); 3. Subchronic supplementation with folic acid 5 mg/kg for 7 days (F) and 4. Subchronic supplementation with F + single dose of H (FH). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. For EEG recordings, three gold-plated recording electrodes were implanted into the skull. Subchronic supplementation with folic acid did not affect seizure incidence, median number of seizure episodes and severity in FH, comparison with H (p > 0.05). The majority of seizure episodes in all groups were of grade 2. There were no significant differences in lethal outcomes at 24 h upon H injection in the FH vs. H group. The activity of Na⁺/K⁺-ATPase and Mg²âº-ATPase was significantly increased in almost all examined structures in the FH vs. H group. Subchronic folic acid administration did not exacerbate H induced seizures and completely recovered the activity of ATPases.

[CROATIAN GUIDELINES FOR IN VITRO DIAGNOSIS OF IgE MEDIATED HYPERSENSITIVITY].

In vitro diagnostic procedure in allergology includes determination of serum levels of total and allergen specific IgE antibodies, allergen specific IgG antibodies, plasma tryptase, eosinophil cationic protein (ECP) and basophil activation test (BAT). In vitro tests should be used according to clinical history, physical examination, and in vivo methods for allergy testing. Clinical relevance of elevated total IgE in allergy diagnosis is modest, since it can be caused by other conditions. Elevated serum levels of allergen specific IgE antibodies, together with positive medical history, are indicative of clinically relevant allergy. A recommended laboratory method for total and specific IgE concentration measurement is the sandwich-type fluoroimmunoassay ImmunoCAP, considered as an ideal immunoassay. Serum levels of allergen specific IgG antibodies have no proved clinical relevance in food allergy diagnosis. They can be useful to monitor venom immunotherapy success, as well as to estimate the risk of venom induced anaphylaxis. Elevated plasma tryptase (subtype ß) level is an indication of mast cell activation caused by specific allergen. It should be obtained within 4 hours after an anaphylactic episode. Elevated level of ECP can be detected in patient blood during late phase of allergic reaction. It can be used to monitor patients with chronic allergenic and inflammatory conditions in which eosinophils play a central role. BAT includes measurement of CD 63 (cluster of differentiation) and CD 203 antigens of the molecular surface by flow cytometry. It is useful in the diagnosis of venom, food and drug allergy, estimation of severity of allergic disease and natural tolerance to allergens. In vitro tests based on allergen extracts can be used for in vitro diagnosis in monosensitized patients with clear medical history and symptomatic treatment. Molecular allergy diagnosis should be performed in special clinical indications such as diagnosis of cross reactivity, prescription of specific immunotherapy (especially in polysensitized patients with complex symptoms), diagnosis of idiopathic or cofactor induced anaphylaxis, latex allergy, and assessment of the risk of allergic reaction to specific allergen.

House dust mite subcutaneous immunotherapy does not induce new sensitization to tropomyosin: does it do the opposite?

BACKGROUND: It is still uncertain whether house dust mite (HDM) tropomyosin present in allergen extracts can cross-sensitize patients receiving subcutaneous immunotherapy (SCIT) and thus induce food allergy. OBJECTIVES: Our aim was to assess whether new sensitization to tropomyosin occurred during HDM-SCIT, and, if so, whether it was clinically relevant. PATIENTS AND METHODS: The study sample comprised 56 HDM-allergic patients treated with SCIT using HDM extract. All patients were screened for specific IgE (sIgE) to mite tropomyosin (rDer p 10) before and after SCIT. In patients with a positive result, we also monitored the dynamics of sIgE to rDer p 10 and shrimp tropomyosin (rPen a 1) at several time points. The levels of sIgE were measured using the CAP System fluorescent-enzyme immunoassay. RESULTS: sIgE to tropomyosin was found in only 5 patients, 3 of whom expressed low and clinically irrelevant levels of sIgE to Der p 10, while sIgE to Pen a 1 was not found. The remaining 2 patients expressed sIgE to both tropomyosins. In the first, the initial increase and subsequent decrease resembled the dynamics of the IgE antibodies usually seen in SCIT patients and were never accompanied by seafood-induced symptoms. In the other, a decrease in levels of sIgE to both tropomyosins resulted in the complete loss of his reactivity toward seafood. CONCLUSIONS: Immunotherapy using HDM extracts does not induce clinically relevant sensitization to tropomyosin. In certain cases of combined mite and seafood allergy, treatment may even lead to the improvement of food allergy symptoms. The levels of sIgE to Der p 10 and Pen a 1 may be useful monitoring markers.

House dust mite subcutaneous immunotherapy does not induce new sensitization to tropomyosin: does it do the opposite?

Background: It is still uncertain whether house dust mite (HDM) tropomyosin present in allergen extracts can cross-sensitize patients receiving subcutaneous immunotherapy (SCIT) and thus induce food allergy. Objectives: Our aim was to assess whether new sensitization to tropomyosin occurred during HDM-SCIT, and, if so, whether it was clinically relevant. Patients and Methods: The study sample comprised 56 HDM-allergic patients treated with SCIT using HDM extract. All patients were screened for specific IgE (sIgE) to mite tropomyosin (rDer p 10) before and after SCIT. In patients with a positive result, we also monitored the dynamics of sIgE to rDer p 10 and shrimp tropomyosin (rPen a 1) at several time points. The levels of sIgE were measured using the CAP System fluorescent-enzyme immunoassay. Results: sIgE to tropomyosin was found in only 5 patients, 3 of whom expressed low and clinically irrelevant levels of sIgE to Der p 10, while sIgE to Pen a 1 was not found. The remaining 2 patients expressed sIgE to both tropomyosins. In the first, the initial increase and subsequent decrease resembled the dynamics of the IgE antibodies usually seen in SCIT patients and were never accompanied by seafood-induced symptoms. In the other, a decrease in levels of sIgE to both tropomyosins resulted in the complete loss of his reactivity toward seafood. Conclusions: Immunotherapy using HDM extracts does not induce clinically relevant sensitization to tropomyosin. In certain cases of combined mite and seafood allergy, treatment may even lead to the improvement of food allergy symptoms. The levels of sIgE to Der p 10 and Pen a 1 may be useful monitoring markers (AU)

Antecedentes: Es un hecho incierto que la tropomiosina presente en los extractos alergénicos puede sensibilizar a los pacientes que reciben inmunoterapia Ag-específica e inducir alergia alimentaria. Objetivo: El objetivo de este estudio fue evaluar si una inmunoterapia subcutánea con extractos de ácaros del polvo de casa puede inducir a una sensibilización a tropomiosina y si esta podría ser clínicamente relevante. Métodos: Se incluyeron en el estudio 56 pacientes alérgicos al ácaro del polvo de casa, tratados con un extracto de ácaros. En todos los pacientes se analizó la IgE esp frente a tropomiosina del ácaro (rDer p 10) antes y después de la IT. En los pacientes con resultado positivo tambien se monitorizó la IgE esp frente a las tropomiosinas del ácaro y de la gamba (rPen a 1) en varios tiempos, mediante CAP-System FEIA. Resultados: En cuanto a los resultados obtenidos, la IgE esp frente a tropomiosina fue positiva únicamente en 5 pacientes, tres de los cuales mostraban valores bajos y clínicamente irrelevantes de IgE esp frente a Der p 10 y no se encontró en ningún caso IgE esp positiva frente a Pen a 1. Los otros dos pacientes mostraron IgE esp positiva a ambas tropomiosinas. En el primero de ellos se observó un incremento inicial y una posterior disminución tras la IT, dinámica similar a la observada habitualmente con los anticuerpos IgE en los pacientes sometidos a inmunoterapia subcutánea y que nunca se acompañaba de síntomas con la ingesta de marisco. En el otro caso, la disminución de la IgE esp frente a ambas tropomiosinas resultó en la completa pérdida de reactividad frente a marisco. Conclusiones: En conclusión, la inmunoterapia frente a ácaros del polvo de casa no induce a una sensibilización a tropomiosina clínicamente relevante. En algunos casos, la alergia frente a ácaros y marisco tratada con IT puede mejorar los síntomas de la alergia alimentaria. Los niveles de IgE específica frente a Der p 10 y Pen a 1 pueden ser marcadores útiles para monitorizar a estos pacientes (AU)

Homocysteine thiolactone-induced seizures in adult rats are aggravated by inhibition of inducible nitric oxide synthase.

Homocysteine and its metabolites (homocysteine thiolactone (HT)) induce seizures via different but still not well-known mechanisms. The role of nitric oxide (NO) in epileptogenesis is highly contradictory and depends on, among other factors, the source of NO production. The aim of the present study was to examine the effects of aminoguanidine, selective inhibitor of inducible NO synthase (iNOS), on HT-induced seizures. Aminoguanidine (50, 75, and 100 mg/kg, intraperitoneally (i.p.)) was injected to rats 30 min prior to inducing HT (5.5 mmol/kg, i.p.). Seizure behavior was assessed by seizure incidence, latency time to first seizure onset, number of seizure episodes, and their severity during observational period of 90 min. Number and duration of spike and wave discharges (SWDs) were determined in electroencephalogram (EEG). Seizure latency time was significantly shortened, while seizure incidence, number, and duration of HT-induced SWD in EEG significantly increased in rats receiving aminoguanidine 100 mg/kg before subconvulsive dose of HT. Aminoguanidine in a dose-dependent manner also significantly increased the number of seizure episodes induced by HT and their severity. It could be concluded that iNOS inhibitor (aminoguanidine) markedly aggravates behavioral and EEG manifestations of HT-induced seizures in rats, showing functional involvement of iNOS in homocysteine convulsive mechanisms.

Exercise decreases susceptibility to homocysteine seizures: the role of oxidative stress.

The aim of the study was to examine the effects of chronic exercise training on seizures induced by homocysteine thiolactone (HCT) in adult rats. Rats were assigned to: sedentary control; exercise control; sedentary+HCT; exercise+HCT group. Animals in the exercise groups ran 30 min daily on a treadmill for 30 consecutive days (belt speed 20 m/min), while sedentary rats spent the same time on the treadmill (speed 0 m/min). On the 31st day, the HCT groups received HCT (8.0 mmol/kg), while the control groups received vehicle. Afterwards, convulsive behavior and EEG activity were registered. Lipid peroxidation, superoxide dismutase (SOD) and catalase (CAT) activity were ascertained in the rat hippocampus. No signs of seizures were registered in sedentary and exercise control rats. Seizure latency was increased, while number of seizure episodes and spike-and-wave discharges (SWD) in EEG were decreased in the exercise+HCT compared to the sedentary+HCT group. Seizure incidence, the severity thereof and duration of SWDs were not significantly different between these groups. Exercise partly prevented increase of lipid peroxidation and decrease of the SOD and CAT activity after HCT administration. These results indicate beneficial effects of exercise in model of HCT-induced seizures in rats, what could be, at least in part, a consequence of improved antioxidant enzymes activity.

Spectral analysis of thioacetamide-induced electroencephalographic changes in rats.

Thioacetamide (TAA) is widely used as a model of hepatic encephalopathy (HE). The aim of our study was to investigate the effects of TAA on electroencephalographic (EEG) changes in rats and to compare them with human HE. Male Wistar rats were divided into groups: (1) saline-treated group and (2) TAA-treated groups: TAA(300) (300 mg/kg), TAA(600) (600 mg/kg), and TAA(900) (900 mg/kg). Daily dose of TAA (300 mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)), or thrice (TAA(900)) in subsequent days. EEG changes were recorded about 24 h after the last dose of TAA. Absolute and relative power density in alpha bands were significantly higher in TAA(300) versus control group. In TAA(300), absolute beta power density was higher and relative beta power density was lower versus control group. Absolute alpha, theta, delta, and relative theta power were significantly lower, while relative power in delta band was significantly higher in TAA(900) versus control group (p < 0.01). In conclusion, decrease in EEG voltage with an increase in delta relative power, which correspond to the EEG manifestations of severe HE in humans, was observed in TAA(900) group. Electrical activity in TAA(300) group correlates with mild HE in humans.

Endoscopic ultrasound for differential diagnosis of duodenal lesions.

PURPOSE: Duodenal tumors are rare and require a different management from that of esophagogastric neoplasia. The present study retrospectively analyses the endoscopic ultrasound (EUS) features of duodenal tumors of both epithelial and subepithelial origin. MATERIALS AND METHODS: During a 12 year period, all duodenal tumors with histologic confirmation by surgery or biopsy were collected including endoscopic and endosonographic images. EUS images were analyzed for specific features (echogenicity, wall layer structure and relation, outer margins) to possibly distinguish epithelial (polyps and carcinoma versus lymphoma) and subepithelial (tumor type) tumors. RESULTS: 53/80 cases had histologic confirmation (mean age 53.1 ±â€Š11.4 years, m:f = 33:20), 31 were epithelial (13 adenomas, 12 carcinomas, 6 lymphomas) and 22 subepithelial (11 GISTs, 7 Brunneromas, 1 lipoma, 3 NETs). EUS did not recognize carcinomas in 2/13 adenomas. EUS features suggesting carcinoma were loss of wall layers and irregular margins. 5/6 lymphomas showed inhomogeneous thickening with layers partially recognizable. Tumor type of subepithelial lesions correlated with echogenicity: GIST tumors were mostly (62.5 %) hypocheoic with the 3 malignant cases being characterized by heterogeneous echopattern with irregular outer margins. Of the hyperechoic lesions, lipomas had a homogeneous whitish appearance, while NET and Brunneromas were less hyperechoic. In the latter, the endoscopic aspect was also helpful for differential diagnosis. Accuracy of combined endoscopic/EUS imaging for all duodenal lesions was 84.9 % (45/53). No procedural complications occurred among all patients that received EUS examinations. CONCLUSION: EUS contributes to the differential diagnosis of epithelial lesions known to be malignant; in subepithelial tumors, tissue confirmation is still required.

An Evaluation of European Countries' Health Systems through Distance Based Analysis.

INTRODUCTION: The issue of evaluating the efficiency of health systems has been elaborated upon frequently. Since "health" is a multi-faceted concept, many variables of different measurement units must be included in its analysis; consequently, this presents a great obstacle for researchers to overcome. MATERIALS AND METHODS: A novel statistical approach for evaluating the efficiency of organizational units is here proposed, which can also be easily applied to the health sector. For these purposes, the health status of the 27 countries belonging to the European Union has been examined by employing a statistical Ivanovic-Jeremic Distance Based Analysis (DBA) on various health indicators. RESULTS: The subsequent outcome of the Distance Based Analysis has shown that Cyprus and Ireland have a most efficient health system sectors. Greece also has exceptional indicators of health service, yet health on the individual level is not comparable. LIMITATIONS: Since it synthesizes many variables into an efficiency score, a DBA can be easily applied to other regions/countries. However, the choice of input and output variables can be considered to be potential limitations since a different choice of variables may cause different efficiency scores for the countries selected. CONCLUSIONS: A DBA approach contributes significantly to the efficiency in the field of research measurement. This analysis can be additionally performed alongside DEA and SFA methods, as a new measure of efficiency.

Autoimmune polyglandular syndrome type 2 shows the same HLA class II pattern as type 1 diabetes.

Autoimmune polyglandular syndrome (APS) type 2 is defined by the manifestation of at least two autoimmune endocrine diseases. Only few data exist on genetic associations of APS type 2. In this controlled study, 98 patients with APS type 2, 96 patients with type 1 diabetes (T1D), and 92 patients with autoimmune thyroid disease, both as a single autoimmune endocrinopathy, were tested for association with alleles of the human leukocyte antigen (HLA) class II loci DRB1, DQA1, and DQB1. Patients with APS type 2 had significantly more often the alleles DRB1*03 (P(c) < 0.0001), DRB1*04 (P(c) < 0.000005), DQA1*03 (P(c) < 0.0001), and DQB1*02 (P(c) < 0.05), when compared with controls. Less frequent in APS were DRB1*15 (P(c) < 0.05), DQA1*01 (P(c) < 0.0005), and DQB1*05 (P(c) < 0.005). With regard to frequency and linkage of these alleles, the susceptible haplotypes DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*0401/04-DQA1*0301-DQB1*0302 were deduced. Protective haplotypes in this study were DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*0101-DQA1*0101-DQB1*0501. Comparing APS patients with vs without AD, no significant differences regarding HLA class II alleles were noted in our collective. Patients with T1D as a singular disease had the same susceptible and protective HLA alleles and haplotypes. The prevalence of DRB1*03 and DRB1*04 in APS patients was not because of the presence of diabetes, as the APS type 2 patients without diabetes had the same allele distribution. In conclusion, these data suggest a common immunogenetic pathomechanism for T1D and APS type 2, which might be different from the immunogenetic pathomechanism of other autoimmune endocrine disease.

The effect of N-methyl-D-aspartate receptor antagonists on D,L-homocysteine thiolactone induced seizures in adult rats.

The aim of our study was to investigate the effects of ifenprodil and MK-801 on D,L-homocysteine thiolactone induced seizures in adult rats.Male Wistar rats were divided into following groups: 1. Saline-treated (C, n=10); 2. D,L-homocysteine thiolactone 8 mmol/kg, i.p. (H, n=7); 3. Ifenprodil 20 mg/kg i.p. (IF, n=8); 4. MK-801 0.5 mg/kg, i.p. (MK, n=8) and 5. Groups that received IF or MK 30 minutes prior to H (IFH, n=8 and MKH, n=8). Seizure behavior was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. Lethality in experimental group was recorded 90 min and 24 h upon D,L-homocysteine thiolactone administration.There were no behavioral signs of seizure activity in groups C, IF and MK.Pre-treatment with MK-801 (MKH) showed tendency to reduced incidence of convulsions, latency to the first seizure onset and the severity of seizure episodes, but statistical significance was not attained comparing to the H group. However, median number of seizure episodes was significantly decreased in MKH (p<0.05), comparing to the H group. On the other hand, ifenprodil (IFH) decreased the latency to the first seizure onset and increased the median number of seizure episodes (p<0.05). The majority of seizure episodes in IFH (72.1%, p<0.05) and MKH (73.1%, p<0.05) groups was grade 2 and significantly different comparing to the H (36.0%). Our findings suggest that MK-801 has a mild anticonvulsive effect on D,L-homocysteine thiolactone induced seizures in adult rats.

Viruses and bacteria in acute asthma exacerbations--a GA² LEN-DARE systematic review.

A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

The correlation between lipid peroxidation in different brain regions and the severity of lindane-induced seizures in rats.

The aim of this study was to investigate the dynamics of lipid peroxidation and the possible correlation between lipid peroxidation in different brain regions and behavioral manifestations in lindane-induced seizures in rats. Male Wistar rats were divided into the following groups: 1. control, saline-treated group; 2. dimethylsulfoxide (DMSO)-treated group; 3. lindane-treated group (8 mg/kg), intraperitoneally. Animals were sacrificed 0.5 or 4 h after treatment and the malondialdehyde level and superoxide dismutase (SOD) activity were determined in various brain regions spectrophotometrically. Behavioral changes were classified according to the descriptive scale (0--no response, 1--head nodding, lower jaw twitching; 2--myoclonic body jerks, bilateral forelimb clonus with full rearing; 3--progression to generalized clonic convulsions followed by tonic extension of fore- and hind limbs and tail; 4--status epilepticus). A significant rise in the malondialdehyde level was detected in the cerebral cortex, hippocampus, and thalamus of lindane-treated animals 0.5 and 4 h after administration (P < 0.05). SOD activity (total and mitochondrial) was significantly decreased in the hippocampus and the cortex of lindane-treated animals at both time points (P < 0.05). An initial fall in SOD activity was detected in the thalamus 4 h after lindane administration (P < 0.05). A positive correlation between seizure severity and the malondialdehyde level was found in the hippocampus at both time points (P < 0.01). These results suggest that lipid peroxidation may contribute to the neurotoxic effects of lindane in early acute lindane intoxication and that behavioral manifestations correlate with lipid peroxidation in the hippocampus of lindane-treated rats.