Early cardiac injury in acute respiratory distress syndrome: comparison of two experimental models.

Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung damage, inflammation, oedema formation, and surfactant dysfunction leading to hypoxemia. Severe ARDS can accelerate the injury of other organs, worsening the patient´s status. There is an evidence that the lung tissue injury affects the right heart function causing cor pulmonale. However, heart tissue changes associated with ARDS are still poorly known. Therefore, this study evaluated oxidative and inflammatory modifications of the heart tissue in two experimental models of ARDS induced in New Zealand rabbits by intratracheal instillation of neonatal meconium (100 mg/kg) or by repetitive lung lavages with saline (30 ml/kg). Since induction of the respiratory insufficiency, all animals were oxygen-ventilated for next 5 h. Total and differential counts of leukocytes were measured in the arterial blood, markers of myocardial injury [(troponin, creatine kinase - myocardial band (CK-MB), lactate dehydrogenase (LD)] in the plasma, and markers of inflammation [tumour necrosis factor (TNF)alpha, interleukin (IL)-6], cardiovascular risk [galectin-3 (Gal-3)], oxidative changes [thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine (3NT)], and vascular damage [receptor for advanced glycation end products (RAGE)] in the heart tissue. Apoptosis of heart cells was investigated immunohistochemically. In both ARDS models, counts of total leukocytes and neutrophils in the blood, markers of myocardial injury, inflammation, oxidative and vascular damage in the plasma and heart tissue, and heart cell apoptosis increased compared to controls. This study indicates that changes associated with ARDS may contribute to early heart damage what can potentially deteriorate the cardiac function and contribute to its failure.

The age at onset in Multiple Sclerosis is associated with patient's prognosis.

BACKGROUND: The causes of the individual differences in the rate of disability progression in multiple sclerosis (MS) are still not completely clear. According to the long-term prognosis of MS patients, the search for new valuable prognostic markers of "benign" or "malign" MS is necessary. OBJECTIVES: Our aim was to assess the possible association of MS onset age with the disease disability progression rate in Slovak patients with MS. METHODS: By the unique pattern of evaluation of disability progression rate using Multiple Sclerosis Severity Score (MSSS), each of 270 MS patients was defined as slow-progressing, mid-rate progressing or rapidly progressing. RESULTS: We found a significant differences in the age at onset between MS patients with different rate of disability progression (p(K-W)<0,00005). The faster was a disability progression assessed by MSSS score, the higher was the MS onset age. CONCLUSION: We showed for the first time in Central European Slovak population that MS onset age is an early marker that is in the positive correlation with disease disability progression rate, evaluated by MSSS score. We conclude that relapsing-remitting MS patients older at clinical onset have a higher risk of unfavorable prognosis (Tab. 2, Fig. 1, Ref. 21).

Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue.

OBJECTIVES: Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area. METHOD: 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale. RESULTS: Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1-2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse. CONCLUSION: Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.

Lung inflammatory and oxidative alterations after exogenous surfactant therapy fortified with budesonide in rabbit model of meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5 h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/ proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-alpha) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.

Thyrotropin versus thyroid hormone in regulating bone density and turnover in premenopausal women.

OBJECTIVE: This cross-sectional study aimed to evaluate the interrelations between endogenous TSH level on one side and the status of bone mineral density (BMD) and bone metabolic turnover (BMT) on the other in pooled four groups of premenopausal women either without or with a long-term L-thyroxine treatment. METHODS: Serum levels of free thyroxine (FT4), thyrotropin (TSH), calcium (Ca), alkaline phosphatase (ALP), osteocalcin OC) and cross linked N-telopeptide of type 1 collagen (NTx) as well as urinary calcium (U-Ca/24h), bone mineral density of lumbar spine L 1-4 (BMD-L) and femoral hip (BMD-F) were estimated in a cohort of 151 premenopausal women (median 36 years) consisting of four groups: Group 1, 40 healthy untreated women, while three other groups consisted of patients previously treated for about 5 years; Group 2, 41 patients with genuine hypothyroidism treated by L-thyroxine (50-100 microg daily); Group 3, 40 patients with genuine hyperthyroidism treated by Carbimazol (10-15 mg daily); Group 4, 30 patients treated by suppressive doses of L-thyroxine (100-150 microg daily) after thyroidectomy for thyroid cancer (n=10) or because of progressively growing benign goitre (n=20). RESULTS: When using multiple correlation analysis (Pearson's r) in pooled 151 women, TSH showed significant positive correlation with BMD-L (p<0.01) and BMD-F (p<0.001) and, at the same time, significant negative correlation with serum level of BMT markers such as ALP (p<0.05), OC (p<0.05) and NTx (p<0.01), while the correlation of FT4 with BMD-L, BMD-F was significantly negative (p<0.001 for both) and that with all BMT markers was significantly positive (p<0.05 to <0.001). Thus, it appeared that higher TSH level was associated with increased bone mineral density and, at the same, with decreased bone metabolic turnover. These interrelations were further supported by the findings of significantly lower BMD-F (p<0.01), BMD-L (p<0.001) and significantly higher ALP, OC and NTX (all at p<0.001) in the group of 36 women with TSH level<0.3 mU/l as compared to the group of 115 women with TSH level range of 0.35-6.3 mU/l). CONCLUSIONS: Irrespectively of thyroid diagnosis and/or previous long term thyroxine treatment in some groups, this cross sectional study showed that, after the pooled group of 151 women has been redistributed according to the actual TSH level, the bone mineral density and the level of bone turnover markers was significantly more favorable in 115 subjects with TSH level range of 0.35-6.3 mU/l than these in 36 women with TSH<0.3 mU/l.

The level of TSH appeared favourable in maintaining bone mineral density in postmenopausal women.

OBJECTIVE: Since the positive role of thyrotropin (TSH) in bone remodeling has been recently emphasized, this cross-section study is aimed to evaluate the association of bone status with the level of TSH and free thyroxine (FT4) in the cohort of postmenopausal women after long-term treatment of thyroid disorders and age matched controls. METHODS: Urinary calcium (dUCa) and serum level of TSH, FT4 and of bone turnover markers (BTMs) such as alkaline phosphatase (ALP), osteocalcin (OC), cross linked N-telopeptide of type 1 collagen (NTx) as well as lumbar spine L 1-4 (BMD-L) and femoral hip (BMD-F) mineral density were determined in 113 postmenopausal women consisting of 42 patients with Graves disease treated by carbimazole, 32 patients with thyroid cancer treated with L-thyroxine and 39 age matched women without any thyroid and osteological disorders. For statistical evaluation t-test, Pearson's correlation coefficient and linear multiple regression were used. RESULTS: To compare the association of TSH versus FT4 with BMD and BTMs the pooled cohort of all 113 women was divided in two groups in terms of TSH level: 1. 34 women with low TSH (>or=0.50 mU/l); 2. 79 women with normal TSH (0.51-4.3 mU/l). In spite of significantly higher FT4 level, the Group 2 with normal TSH level had significantly higher BMD-L and BMD-F (p<0.001) and, in contrast, significantly lower urinary dUCa, ALP, OC (all at p<0.001) and NTx (p<0.01) as compared to the Group 1 with low TSH level. Linear multiple regression showed highly significant influence of TSH on BMD-L and BMD-F0 (p<0.001) independent of age, FT4 and body mass index, while that of FT4 was not significant. The strength of linear interrelation between all variables used was finally tested by Pearson's correlation coefficient (Table 3) which was highly positive for TSH with BMD-F and BMD-L, but highly negative for TSH with serum NTx, OC, ALP) and urinary calcium (dUCa). In contrast, no significant correlation was found between the level of FT4 and BMD. CONCLUSIONS: Irrespectively of FT4 level, postmenopausal women with normal TSH level showed a favorable bone status as compared to these with low level of TSH which is consistent with the view that TSH itself possibly participates in playing a favorable role in influencing the bone mineral density in adult women.

Preferences of patients with post-menopausal osteoporosis treated with bisphosphonates--the VIVA II study.

The effectiveness of bisphosphonate treatment for post-menopausal osteoporosis depends on patients adhering to the therapeutic regimen. We previously showed that patients prefer a once-monthly regimen and the present follow-up study aimed to analyse patients' motivation for this preference. Women with post-menopausal osteoporosis (n = 2035) completed a questionnaire targeting their bisphosphonate treatment preferences. The majority had chosen the once-monthly regimen due to the comfort (69%) and simplicity (59%) of the treatment and the need to take fewer pills (55%). Friends, relatives and print media were highlighted as important sources of information and many patients indicated a need for more information about osteoporosis and its management. Gastrointestinal and muscular side-effects were reported by about one-third of the patients, but these were well tolerated. It is concluded that once-monthly bisphosphonate treatment was preferred due to improved quality of life and should be offered to all patients with post-menopausal osteoporosis.