The Potassium Channel Kv1.5 Expression Alters During Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease with an autoimmune component. It was suggested that potassium channels, which are involved in crucial biological functions may have a role in different diseases, including MS and its animal model, experimental autoimmune encephalomyelitis (EAE). It was shown that voltage-gated potassium channels Kv1.5 are responsible for fine-tuning in the immune physiology and influence proliferation and differentiation in microglia and astrocytes. Here, we explored the cellular distribution of the Kv1.5 channel, together with its transcript and protein expression in the male rat spinal cord during different stages of EAE. Our results reveal a decrease of Kv1.5 transcript and protein level at the peak of disease, where massive infiltration of myeloid cells occurs, together with reactive astrogliosis and demyelination. Also, we revealed that the presence of this channel is not found in infiltrating macrophages/microglia during EAE. It is interesting to note that Kv1.5 channel is expressed only in resting microglia in the naïve animals. Predominant expression of Kv1.5 channel was found in the astrocytes in all experimental groups, while some vimentin+ cells, resembling macrophages, are devoid of Kv1.5 expression. Our results point to the possible link between Kv1.5 channel and the pathophysiological processes in EAE.

Coxiella burnetii chronic pericarditis: a case report.

Coxiella burnetii is capable of causing a variety of acute and chronic infections. We present a case of pericarditis with serologically confirmed chronic C. burnetii infection. This case report emphasises the justification of serological testing for chronic C. burnetii infection in patients with prolonged or recurrent pericarditis, particularly in countries endemic for C. burnetii infection.

Hypothalamic-pituitary-adrenocortical axis hypersensitivity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome.

INTRODUCTION: Molecular mechanisms underlying pathophysiology of polycystic ovary syndrome (PCOS), especially those related to cortisol signaling, are poorly understood. We hypothesized that modulation of glucocorticoid receptor (GR) expression and function, may underlie possible PCOS-related impairment of feedback inhibition of hypothalamic-pituitary-adrenocortical (HPA) axis activity and thus contribute to increased adrenal androgen production in women with PCOS. MATERIALS AND METHODS: 24 normal-weight and 31 obese women with PCOS were compared to 25 normal-weight controls. Fasting blood samples were collected for measurements of serum concentrations of dehydroepiandrosterone sulfate, testosterone, sex hormone-binding globulin, insulin, basal cortisol and cortisol after oral administration of 0.5 mg dexamethasone. Concentrations of GR mRNA, GR protein, mineralocorticoid receptor (MR) protein and heat shock proteins (Hsps), as well as the number of GR per cell (B(max)) and its equilibrium dissociation constant (K(D)) were measured in isolated peripheral blood mononuclear cells. RESULTS: An increase in HPA axis sensitivity to dexamethasone, an elevation of the GR protein concentration, and unaltered receptor functional status were found in both normal-weight and obese women with PCOS vs. healthy controls. Lymphocyte MR, Hsp90 and Hsp70 concentrations, and MR/GR ratio were similar in all groups. Correlation between B(max) and K(D) was weaker in the group of obese women with PCOS than in the other 2 groups. CONCLUSIONS: The results did not confirm the initial hypothesis, but imply that PCOS is associated with increased GR protein concentration and HPA axis sensitivity to dexamethasone.

Insulin resistance in non-obese women with polycystic ovary syndrome: relation to byproducts of oxidative stress.

To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was significantly higher (p < 0.05) in PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also significantly elevated in PCOS (p < 0.05). Both plasma SOD and GPX activity showed no statistically significant difference between PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p < 0.05) as well as GPX activity (r = 0.531 and r = 0.358, respectively; p < 0.05). Our results indicate that insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS.

Trends in myocardial infarction in Middle Dalmatia during the war in Croatia.

The aim of this study was to determine the pattern of myocardial infarction (MI) incidence with regard to age, gender, infarction site, and the most important risk factors. All 3,454 patients hospitalized in coronary care units of Clinical Hospital Split between 1989 and 1997 were analyzed. In the 3-year period preceding the war, from 1989 to 1991, 1,024 patients were hospitalized because of MI. During the 3 years of full war activities, from 1992 to 1994, there were 1,257 patients (significantly more; p < 0.05). And in the 3-year period after the war, from 1995 to 1997, there were 1,173 patients. In the war period, there were 151 (12%) patients younger than 45 years of age (p < 0.05); of that number, 143 (95%) were men (significantly more than in the other two periods; p < 0.05) and 8 (5%) were women. In the period preceding the war, there were 66 (6.5%) patients younger than 45 years: 60 (91%) men and 6 (9%) women. In the period after the war, those numbers were 88 (7.5%), 81 (92%), and 7 (8%), respectively. The patients younger than 45 years (305) more often had MI of an inferior than an anterior site (49% vs. 28%; p < 0.001), whereas there was no difference in patients older than 45 years (36% vs. 37%; p > 0.05). The patients older than 45 years had significantly greater hospital mortality (21% vs. 4%; p < 0.001) and were more likely to have hypertension (51% vs. 15%; p < 0.001) as well as hypercholesterolemia (54% vs. 14%; p < 0.001). Smokers prevailed among those younger than 45 years (75% vs. 51%; p < 0.001). The number of hospitalized patients with MI was greatest during the war period. It included a significant increase in the incidence in men younger than 45 years (12% vs. 7%; p < 0.05), with smoking as the most important risk factor, especially for infarctions of inferior sites.

Popliteal artery entrapment syndrome: diagnosis and management, with report of three cases.

Popliteal artery entrapment syndrome is an important albeit infrequent cause of serious disability among young adults and athletes with anomalous anatomic relationships between the popliteal artery and surrounding musculotendinous structures. We report our experience with 3 patients, in whom we used duplex ultrasonography, computed tomography, digital subtraction angiography, and conventional arteriography to diagnose popliteal artery entrapment and to grade the severity of dynamic circulatory insufficiency and arterial damage. We used a posterior surgical approach to give the best view of the anatomic structures compressing the popliteal artery. In 2 patients, in whom compression had not yet damaged the arterial wall, operative decompression of the artery by resection of the aberrant muscle was sufficient. In the 3rd patient, operative reconstruction of an occluded segment with autologous vein graft was necessary, in addition to decompression of the vessel and resection of aberrant muscle. The result in each case was complete recovery, with absence of symptoms and with patency verified by Doppler examination. We conclude that clinicians who encounter young patients with progressive lowerlimb arterial insufficiency should be aware of the possibility of popliteal artery entrapment. Early diagnosis through a combined approach (careful physical examination and history-taking, duplex ultrasonography, computerized tomography, and angiography) is necessary for exact diagnosis. The treatment of choice is the surgical creation of normal anatomy within the popliteal fossa.

Dermatological indicators of coronary risk: a case-control study.

OBJECTIVE: We examined the association of dermatological signs such as baldness, thoracic hairiness, hair greying and diagonal earlobe crease with the risk of myocardial infarction in men under the age of 60 years. METHODS: A hospital-based, case-control study included 842 men admitted for the first non-fatal myocardial infarction, the controls were 712 men admitted with noncardiac diagnoses, without clinical signs of coronary disease. The relative risks were estimated as odds ratios. Logistic regression was used to control for the confounding variables. RESULTS: Baldness, thoracic hairiness and earlobe crease were approximately 40% more prevalent in cases (P<10(-6) in each case). In both cases and controls, baldness and thoracic hairiness were frequently coexistent, as well as hair greying and earlobe crease (P<10(-4) in each case). After allowing for age and other established coronary risk factors, the relative risk of myocardial infarction for fronto-parietal baldness compared with no hair loss was 1.77 (95% CI 1.27-2.45) and it was 1.83 (95 CI 1.4-2.3) for men with thick, extended thoracic hairiness. The presence of a diagonal earlobe crease yielded a relative risk of 1.37 (95% CI 1.25-1.5), while hair greying was associated with myocardial infarction only in men under the age of 50 years. CONCLUSION: It appears that baldness, thoracic hairiness and diagonal earlobe crease indicate an additional risk of myocardial infarction in men under the age of 60 years, independently of age and other established coronary risk factors.

Triggers of acute myocardial infarction regarding its site.

We have studied the incidence of possible triggers of the myocardial infarction regarding its site in 750 patients with anterior and 731 patients with inferior infarction. Infarctions occurred most frequently without recalling any triggering activity, especially in patients with anterior infarction (67 vs. 44%). Physical effort as the possible precipitator was also more frequent in anterior infarctions (22 vs. 16%). However, the onset of inferior infarction was more frequent during meteorological stress (9 vs. 2%), emotional stress (10 vs. 3%), after overeating (13 vs. 3%) and nicotine abuse (6 vs. 1.5%). These triggers were independent and highly significant (P < 0.02 in each case) discriminators of the site of myocardial infarction. Bimodal circadian rhythm, with primary peak between 6 and 9 h a.m. and the secondary peak between 3 and 6 p.m. was observed in patients which did not recall any triggering activity, and this was more pronounced in patients with inferior infarction. These results support the hypothesis that the influence of the vegetative tone is most pronounced in the onset of myocardial infarction of inferior wall.

[Significance of right ventricular dimensions in the differential diagnosis of primary and secondary dilated cardiomyopathy]. / Znacenje promjera desne klijetke u differencijalnoj dijagnostici primarnih i sekundarnih dilatacijskih kardiomioptija.

Numerous analyses are used in the differential diagnosis between primary and secondary dilated cardiomyopathy (PDC, SDC). The aim of this study was to assess the dimensions of heart cavities in patients with dilated cardiomyopathy (DC) by 1-D and 2-D echocardiography. Thirty-six consecutive patients who satisfied the PDC criteria, and 103 patients with criteria of SDC, were followed-up clinically, radiographically, electrocardiographically and by 1-D and 2-D echocardiography, in the period from December 1991 to April 1994, at the Department of Internal Medicine of the Clinical Hospital Split. The patients with PDC were significantly younger than those with SDC (44.4 +/- 10.4: 64.4 +/- 8.4 year). There were significantly more males than females in both DC subgroups. NYHA classification, sinus rhythm and atrial fibrillation did not differ considerably in both DC subcategories. The etiologic factor was ischaemic DC in 85.4% (88/103), systemic arterial hypertension in 11.6% (12/103), and thyrotoxicosis in 2.9% (3/103) of patients with SDC. Alcoholic DC in one patient, peripartal DC in two female patients and viral myocarditis in six patients with PDC were suspected. In the total of 75% (27/36) patients with PDC, a clear etiological factor in case histories was not defined. Left ventricular ejection fraction, diameter and myocardial thickness, as well as left atrium diameter, did not differ significantly in patients with PDC, at variance with SDC patients. Right ventricular enddiastolic diameter (31.55 +/- 4.8 mm: 26.62 +/- 8.6 mm, p < 0.05) and the ratio between enddiastolic diameters of the right and left ventricle were significantly larger in patients with PDC than in those with SDC (0.45 +/- 0.03: 0.37 +/- 0.05, p < 0.05). We conclude that right ventricle is significantly wider in PDC than in SDC patients. Compared with other noninvasive methods, 1-D and 2-D echocardiography is probably the method of choice (particularly in our environment) in the differentiation of primary and secondary DC.

[Dynamic aggregation of thrombocytes in acute myocardial infarct]. / Dinamika agregacije trombocita u akutnom infarktu miokarda.

The dynamics of circulating platelet aggregates (CPA) in acute myocardial infarction (MI) was correlated to its extent, localization and clinical outcome. Creatine kinase (CK) and CPA were measured in 30 patients with acute MI 24 hours after its onset, and on the third, fifth and eighth day following the accident. Twelve patients had anteroseptal MI, another 12 had inferior, and the remaining 6 had non-Q wave MI. 24 hours after the accident CPA values differed significantly between the three groups (p < 0.05). The values of CPA increased with increasing CK. In all the patients CPA and CK returned to normal or almost normal values on days 8 and 5 following MI, respectively. Eleven patients (37%) had heart failure: 8 of them (73%) had anteroseptal MI and 3 had inferior MI (27%). In 10 patients with heart failure (91%) and only in 2 out of 19 patients without heart failure (10.5%), CPA peaked on days 3 or 5 after MI (p < 0.05). In all other patients CPA declined steadily from the initial value. These results suggest that platelet aggregability is significantly associated with the severity of MI and with heart failure.

[Meteorologic effects and thrombocyte aggregation in patients with myocardial infarct living in the coastal region of central Dalmatia]. / Meteoroloska zbivanja i agregacija trombocita u bolesnika s infarktom miokarda na srednjodalmatinskom priobalnom podrucju.

The circulating platelet aggregates were measured in 90 patients admitted to the Clinical Hospital Split because of myocardial infarction developed in the costal region of Middle Dalmatia. They were divided into three groups, each consisting of 30 patients affected by coronary incident developed during the three most characteristic weather types in the region: sirocco, bora and calm weather. All the patients have had elevated values of circulating thrombocyte aggregates, but the patients in the sirocco group exhibited significantly higher values (34.77% +/- 11.67%) than the patients in both bora (27.93% +/- 11.72%; p < 0.05) and the calm weather groups (23.5% +/- 10.62%; p < 0.01). In the control group of 10 healthy examinees the values of circulating platelet aggregates were within normal range during all the three weather types (5.85% +/- 0.70%, 5.24 +/- 0.51% and 5.18 +/- 0.59%, in case of sirocco, bora and calm weather, respectively). The three groups were not significantly different regarding the values of creatinine kinase, which means that the infarct size was not the probable cause of the observed differences in platelet aggregability. Taking into account our previous finding of increased incidence of coronary events during sirocco, these results suggest that increased platelet aggregability is a contributing factor to the risk of myocardial infarction during such a weather.

[The time interval from the onset of myocardial infarct to arrival in the coronary unit in the area of Split]. / Raspon vremena od pocetka infarkta miokarda do dolaska u koronarnu jedinicu na Splitskom podrucju.

The time interval from the initial symptoms of myocardial infarction to the coronary care unit admission in patients treated at the Department of Internal Medicine, University Hospital "Firule", Split, and Military Hospital, Split, between 1 January 1981 and 31 December 1987, vas analysed. The average duration of this delay was 14.8 +/- 11.6 hours (range 2-72 hours). It is concluded that this interval should be substantially reduced in order to decrease the actual coronary heart disease death rate.

[Characteristics of diurnal rhythm in the development of myocardial infarct: risk in the morning hours]. / Osobitosti dnevnog ritma javljanja infarkta miokarda: opasnost jutarnjih sati.

The onset of precordial pain was assessed in all the patients admitted to the Clinical Hospital "Firule" and the Military Hospital, Split, during a six-year period (1981-1986) with acute myocardial infarction (n = 1304). According to the time of onset, all the subjects were stratified in three-hour intervals. The large majority of initial symptoms was registered between 7 and 10 a.m. (372 or 28.53% of all; chi 2 = 317, P less than 0.001). The results of this and other studies of circadian rhythm in coronary events points out to the high risk of morning hours, suggesting specific preventive measures, including pharmacological and life-style interventions.