Transmural distribution of antioxidant defences and lipid peroxidation in the rabbit left ventricular myocardium

The left ventricular subendocardial and subepicardial layers of six perfused rabbit hearts were tested for enzymatic and non-enzymatic antioxidant defences and for lipid peroxidation. The subendocardium showed significantly lower catalase activity and contents of non-protein thiol compounds and vitamin E associated with a higher degree of lipid peroxidation. The activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, -glutamylcysteine synthetase and -glutamyl transpeptidase showed no significant transmural differences, and Se-independent glutathione peroxidase activity was not detectable in either layer. Comparable results were observed in another group of six unperfused rabbit hearts. In five H₂O₂-perfused rabbit hearts, lipid peroxidation was higher, and myocardial creatine phosphokinase activity lower, in the subendocarium than in the subepicardium. In this group, only the subendocardium had significantly higher lipid peroxidation levels than the control hearts. Thus, a lower antioxidant capacity and a greater oxidative stress are present in the rabbit subendocardium. These findings could provide insight into the problem of subendocardial vulnerability to free radical-mediated processes, such as occurs in ischaemia-reperfusion injury.     

Tapering dose of inhaled budesonide in subjects with mild-to-moderate persistent asthma treated with montelukast: a 16-week single-blind randomized study

Pharmacological therapy with inhaled steroids (IS) is currently considered the gold-standard of treatment for mild-persistent asthma. Leukotriene receptor antagonist drugs (LTRAs) play an important role associated with IS, allowing dose tapering and maintaining control of asthma symptoms. The aim of this study was to determine the effectiveness of montelukast (MON) to allow tapering of the inhaled dose of budesonide (BUD) in patients with mild-moderate persistent asthma. This 16-wk single-blind randomized study included 40 asthmatic patients divided in 2 treatment groups. After a run-in period (4 wk), in which all patients inhaled 400 microg of BUD twice daily (bid), group A (20 patients) received MON (oral, 10 mg/day) combined with inhaled BUD (400 microg/bid), while group B (20 patients) was treated with BUD for the whole period of the study. In both groups, at every 4 wk the dose of BUD was halved. After 12 wk of treatment the mean value of forced expiratory volume during the first sec (FEV1, as % of predicted value) was significantly greater in group A compared with group B (94 +/- 7.5 vs 83.1 +/- 6.9; p<0.005). The mean values of peak expiratory flow (PEF), the percentages of asthmatic exacerbations, and the use of beta2-short-acting agonist (SABA) were similar in the 2 groups at 4, 8, and 12 wk. In conclusion, in patients with mild-moderate persistent asthma, MON therapy is useful in tapering the dose of IS in order to reduce its side effects and to maintain the clinical stability of the disease.     

Experimental cryptorchidism inhibited growth of the rat ventral prostate

Adult Sprague-Dawley male rats, weighing about 350 g, were rendered cryptorchid by suturing the testes to the lateral abdominal wall. Twenty-eight days later, cryptorchidism resulted in a significant decline in testis weight and suppressed spermatogenesis. The ventral prostate was significantly smaller in cryptorchid rats. There was no significant difference in serum testosterone levels between the normal and cryptorchid rats. Charcoal-stripped aqueous extracts of the testis from intact and cryptorchid animals were tested on primary cultures of rat prostatic stromal cells. Cultures treated with extract from the intact testis had a significantly increased cell proliferation as assessed by cell count and by the rate of 3H-thymidine incorporation. Additionally, extracts of seminiferous tubules significantly increased prostate stromal cell proliferation compared to extracts of testicular interstitial components. Furthermore, this proliferative effect of testicular extracts is specific to the prostate as extract of both normal and cryptorchid testis stimulated proliferation of rat footsole fibroblasts in culture, but only extracts from intact testis stimulated proliferation of prostate stromal cells. These observations demonstrate that the testis produces nonandrogenic substances that can promote growth of prostatic stromal cells and that these substances were eliminated in the cryptorchid testis.     

Adaptive response of human melanoma cells to methylglyoxal injury

The effects of methylglyoxal on the growth of a line of human melanoma cells are investigated. Methylglyoxal inhibits cell growth in a dose- dependent manner and causes an increase in glyceraldehyde 3-phosphate dehydrogenase, and glyoxalase 1 and glyoxalase 2 specific activities. The cellular response to increasing concentrations of methylglyoxal in the culture medium is also studied by measuring L-lactate production, reduced-oxidized glutathione levels and apoptotic cell death. Methylglyoxal seems to promote a change of cell population phenotypic repertoire toward a more monomorphic phenotype. In conclusion, methylglyoxal seems to induce an enzymatic cellular response that lowers methylglyoxal levels and selects the most resistant cells.      

Lumbar trabecular bone mineral density distribution in patients with and without vertebral fractures: a case–control study

Purpose

The proportion of load transmitted through the lumbar neural arch increases with aging, spinal degeneration, and lordosis, effectively shielding the lumbar vertebral bodies from load. This stress shielding may contribute to bone loss in the vertebral body, leading to increased fracture risk. To test his hypothesis, we performed a study to determine if vertebral body fractures were associated with a higher neural arch/vertebral body volumetric bone mineral density (vBMD) ratio.

Methods

Trabecular vBMD was calculated by quantitative CT in the L3 vertebral body and neural arch (pars interarticularis) of 36 women with vertebral compression fractures and 39 controls. Neural arch/vertebral body vBMD ratio was calculated, and its relationship to fracture status was determined using linear regression models adjusted for age and body mass index.

Results

Vertebral body trabecular vBMD was lower in fracture cases as compared to controls (mean ± SD, 49.0 ± 36.0 vs. 87.5 ± 36.8 mg/cm³, respectively; P < 0.001), whereas trabecular vBMD of the neural arch was similar (96.1 ± 57.6 in cases vs. 118.2 ± 57.4 mg/cm³ in controls; P = 0.182). The neural arch/vertebral body vBMD ratio was significantly greater in the fracture group than in controls (2.31 ± 1.07 vs. 1.44 ± 0.57, respectively; P < 0.001).

Conclusion

These results support the hypothesis that stress shielding is a contributor to vertebral body bone loss and may increase fracture risk. Although further studies are needed, there may be a role for interventions that can shift vertebral loading in the spine to help prevent fracture.     

Bronchial hyperresponsiveness and quality of life in asthmatics

BACKGROUND: Quality of Life (QoL) measurements are more responsive to clinically significant changes that are not evaluated by conventional clinical measures. OBJECTIVE: The objective of this study is to examine the relationship between bronchial hyperresponsiveness (BHR) and QoL in asthmatic patients. PATIENTS AND METHODS: 394 patients underwent clinical follow-up, pulmonary function tests and the methacholine challenge test (MCHt), and completed the Asthma Quality of Life Questionnaire (AQLQ). RESULTS: 200 patients had a positive MCHt and in 194 it was negative. For all 32 items, asthmatic patients had a median value of 4.7 (4.2-5.9) compared to 5.6 (4.7-6.3) in patients with negative MCHt (p < 0.01). For physical activities, patients with positive MCHt showed a median value of 5.0 (4.5-6.0) compared to 5.7 (4.8-6.3) in patients with negative MCHt (p < 0.05). Median scores of 12 items of symptoms and 5 items of emotions were significantly lower in patients with positive MCHt [4.5 (3.7-5.8) and 5.1 (4.2-6.1)] than in patients with negative MCHt [5.5 (4.4-6.1) and 6.3 (5.2-6.9), respectively, (p < 0.01)]. For items of environmental stimuli the median score was 4.7 (3.7-5.9) in patients with positive MCHt, being significantly lower than in patients with negative MCHt [5.4 (4.2-6.4), p < 0.05]. Patients with positive MCHt had lower values of QoL than patients with negative MCHt. CONCLUSIONS: QoL changes may be more sensitive than evaluation of BHR. The measurement of Qol may be important because it enables us to characterize patients who could be candidates eventually to a pharmacological treatment for BHR because they have an impaired QoL.     

Analytical assessment of MALDI-TOF Imaging Mass Spectrometry on thin histological samples. An insight in proteome investigation

BACKGROUND: The development of MALDI Imaging Mass Spectrometry is a promising technique in the investigation of biological molecular repertoire. We have pursued an analytical assessment of this technique in its application to proteome analysis. METHODS: A specific statistical method of analysis has been developed to enable data processing in the absence of internal standards, by defining similarity scores. RESULTS: The investigated linear mode MALDI-TOF set-up allows to obtain data variations comprised within the 30% of variation when assaying tissues samples from the same animal, while the 60% of variation was highlighted in the inter-mice series assaying syngenic animals. CONCLUSIONS: This analytical assessment represents the first step of a process that should validate the utilisation of this technique in the clinical practice.     

An update of the leukotriene modulators for the treatment of asthma

Bronchial asthma is a chronic inflammatory airway disease involving many cells and mediators. Chronic inflammation constitutes an important predisposing condition for airway remodelling with secondary irreversible airflow obstruction. Current approaches for asthma treatment involve many classes of drugs, adequate patient education for their correct use, environmental exposure control and daily monitoring of pulmonary function. Unfortunately, the use of multiple therapies complicates treatment regimens, thus leading to a reduced compliance to therapy. Available evidence from randomised clinical trials and real-word experience derived from managing patients with asthma justifies a broader role for leukotriene receptor antagonist drugs in asthma management than that recommended in the National Asthma Education and Prevention Programme and National Health Lung and Blood Institute Treatment Guidelines. While a low dose of inhaled corticosteroids remains the reference drug as a controller in mild-to-moderate persistent asthma, oral therapy with an leukotriene-receptor antagonist drug represents a good option providing the clinical efficacy requested in common clinical practice. For this reason the recent Global Initiative for Asthma Guidelines allocate this drug to the second and third steps of asthma treatment.     

Glutathione peroxidase, glutathione reductase and glutathione transferase activities in the human artery, vein and heart

The continuous exposure to blood components, including prooxidants, makes the blood vessel wall susceptible to oxidative stress and free radical mediated reactions (Henning and Chow, 1988; Stamm et al., 1989; Halliwell and Gutteridge, 1984). Free radicals can be produced extracellularly via the respiratory bursts of activated neutrophils, or intracellularly, via oxidation of hypoxanthine by xanthine oxidase (Henning and Chow, 1988; Stamm et al., 1989; Rubanyi, 1988). Microsomal enzymes such as lipoxygenase and cyclooxygenase may also be a source of reactive species of oxygen (Henning and Chow, 1988; Stamm et al., 1989; Rubanyi, 1988; Mason et al., 1980). It has been proposed that free radicals are involved in the initiation and progression of various cardiovascular diseases including arteriosclerosis (Henning and Chow, 1988; Stamm et al., 1989; Yagi, 1988; Jürgens et al., 1987). Thus the adequacy of the defence systems against free radicals is critical for the susceptibility of blood vessel wall to oxidative damage. Among the enzymatic systems capable of protecting the cell against oxidative injury, selenium dependent glutathione peroxidase (Se-GSH-px), glutatione reductase (GSSG-rx) and glutathione transferase (GST) play a crucial role (Flohe' et al., 1976; Mannervik and Danielson, 1988). Using glutathione (GSH) as a cofactor, Se-GSH-px reduces H2O2 to water and organic hydroperoxides to the corresponding alcohols (Flohe' et al., 1976). This reaction leads to conversion of GSH into its oxidized form (GSSG). In the presence of NADPH, GSSG-rx is able to reduce the oxidized glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutathione-S-transferase activity from rat placenta

Glutathione S-transferase activity significantly decreased in the rat placenta from the 16th to the 20th day of gestation. Isoelectric focusing of rat placenta supernatant yielded essentially a single peak of glutathione S-transferase activity with I-chloro-2,4-dinitrobenzene as substrate, centred on pH 7.45. Substrate specificity measurements, as well as inhibitory studies, revealed pronounced differences between rat and human placental enzymes. Whether the biochemical differences between rat and human GSH-Trs are reflected in physiological differences remains to be ascertained. The sodium dodecyl sulphate (SDS) gel electrophoresis data on subunit composition showed that the rat enzyme is composed of two identical subunits whose molecular mass closely approaches that of human transferase.