Greater cardiac response of colloid than saline fluid loading in septic and non-septic critically ill patients with clinical hypovolaemia

Background and objective: The haemodynamics of crystalloid and colloid fluid loading may depend on underlying disease, i.e. sepsis versus non-sepsis. Design and setting: A single-centre, single-blinded, randomized clinical trial was carried out on 24 critically ill sepsis and 24 non-sepsis patients with clinical hypovolaemia, assigned to loading with normal saline, gelatin 4%, hydroxyethyl starch 6% or albumin 5% in a 90-min (delta) central venous pressure (CVP)-guided fluid loading protocol. Transpulmonary thermodilution was done each 30 min, yielding, among others, global end-diastolic volume and cardiac indices (GEDVI, CI). Results: Sepsis patients had hyperdynamic hypotension in spite of myocardial depression and dilatation, and greater inotropic/vasopressor requirements than non-sepsis patients. Independent of underlying disease, CVP and GEDVI increased more after colloid than saline loading (P < 0.018), so that CI increased by about 2% after saline and 12% after colloid loading (P = 0.029). The increase in preload-recruitable stroke work was also greater with colloids and did not differ among conditions. Conclusion: Fluid loading with colloids results in a greater linear increase in cardiac filling, output and stroke work than does saline loading, in both septic and non-septic clinical hypovolaemia, in spite of myocardial depression and presumably increased vasopermeability potentially decreasing the effects of colloid fluid loading in the former. © The Author(s) 2010

Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran: a before and after clinical trial

BACKGROUND: Osteoporosis is the gradual declining in bone mass with age, leading to increased bone fragility and fractures. Fractures in hip and spine are known to be the most important complication of the disease which leads in the annual mortality rate of 20% and serious morbidity rate of 50%. Menopause is one of the most common risk factors of osteoporosis. After menopause, sex hormone deficiency is associated with increased remodeling rate and negative bone balance, leading to accelerated bone loss and micro-architectural defects, resulting into increased bone fragility. Compounds with estrogen-like biological activity similar to "Isoflavones" present in plants especially soy, may reduce bone loss in postmenopausal women as they are similar in structure to estrogens. This research, therefore, was carried out to study the effects of Iranian soy protein on biochemical indicators of bone metabolism in osteopenic menopausal women. MATERIALS AND METHODS: This clinical trial of before-after type was carried out on 15 women 45–64 years of age. Subjects were given 35 g soy protein per day for 12 weeks. Blood and urine sampling, anthropometric measurement and 48-h-dietary recalls were carried out at zero, 6 and 12 weeks. Food consumption data were analyzed using Food Proccessor Software. For the study of bone metabolism indicators and changes in anthropometric data as well as dietary intake, and repeated analyses were employed. RESULTS: Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during different stages of the study. Soy protein consumption resulted in a significant reduction in the urinary deoxypyridinoline and increasing of total alkaline phosphatase (p < 0.05), although the alterations in osteocalcin, c-telopeptide, IGFBP3 and type I collagen telopeptide were not significant. CONCLUSION: In view of beneficial effect of soy protein on bone metabolism indicators, inclusion of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis

Mitral Annular Disjunction in Idiopathic Ventricular Fibrillation Patients: Just a Bystander or a Potential Cause?

AIMS: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. METHODS AND RESULTS: This retrospective multicentre study included 185 IVF patients (median age 39 [27, 52] years, 40% female). Cardiac magnetic resonance images were analysed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD(42% vs. 2%, p < 0.001). Proarrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVC) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67% vs. 23%, p < 0.001 and 63% vs 41%, p = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13% vs. 18%, p = 0.579). CONCLUSION: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay

Modulation of Astrocytic Mitochondrial Function by Dichloroacetate Improves Survival and Motor Performance in Inherited Amyotrophic Lateral Sclerosis

Mitochondrial dysfunction is one of the pathogenic mechanisms that lead to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). Astrocytes expressing the ALS-linked SOD1G93A mutation display a decreased mitochondrial respiratory capacity associated to phenotypic changes that cause them to induce motor neuron death. Astrocyte-mediated toxicity can be prevented by mitochondria-targeted antioxidants, indicating a critical role of mitochondria in the neurotoxic phenotype. However, it is presently unknown whether drugs currently used to stimulate mitochondrial metabolism can also modulate ALS progression. Here, we tested the disease-modifying effect of dichloroacetate (DCA), an orphan drug that improves the functional status of mitochondria through the stimulation of the pyruvate dehydrogenase complex activity (PDH). Applied to astrocyte cultures isolated from rats expressing the SOD1G93A mutation, DCA reduced phosphorylation of PDH and improved mitochondrial coupling as expressed by the respiratory control ratio (RCR). Notably, DCA completely prevented the toxicity of SOD1G93A astrocytes to motor neurons in coculture conditions. Chronic administration of DCA (500 mg/L) in the drinking water of mice expressing the SOD1G93A mutation increased survival by 2 weeks compared to untreated mice. Systemic DCA also normalized the reduced RCR value measured in lumbar spinal cord tissue of diseased SOD1G93A mice. A remarkable effect of DCA was the improvement of grip strength performance at the end stage of the disease, which correlated with a recovery of the neuromuscular junction area in extensor digitorum longus muscles. Systemic DCA also decreased astrocyte reactivity and prevented motor neuron loss in SOD1G93A mice. Taken together, our results indicate that improvement of the mitochondrial redox status by DCA leads to a disease-modifying effect, further supporting the therapeutic potential of mitochondria-targeted drugs in ALS

Gene-enhanced tissue engineering for dental hard tissue regeneration: (1) overview and practical considerations

Gene-based therapies for tissue regeneration involve delivering a specific gene to a target tissue with the goal of changing the phenotype or protein expression profile of the recipient cell; the ultimate goal being to form specific tissues required for regeneration. One of the principal advantages of this approach is that it provides for a sustained delivery of physiologic levels of the growth factor of interest. This manuscript will review the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. Part 2 will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Floral odors and the interaction between pollinating Ceratopogonid midges and Cacao

Most plant species depend upon insect pollination services, including many cash and subsistence crops. Plants compete to attract those insects using visual cues and floral odor which pollinators associate with a reward. The cacao tree, Theobroma cacao, has a highly specialized floral morphology permitting pollination primarily by Ceratopogonid midges. However, these insects do not depend upon cacao flowers for their life cycle, and can use other sugar sources. To understand how floral cues mediate pollination in cacao we developed a method for rearing Ceratopogonidae through several complete lifecycles to provide material for bioassays. We carried out collection and analysis of cacao floral volatiles, and identified a bouquet made up exclusively of saturated and unsaturated, straight-chain hydrocarbons, which is unusual among floral odors. The most abundant components were tridecane, pentadecane, (Z)-7-pentadecene and (Z)-8-heptadecene with a heptadecadiene and heptadecatriene as minor components. We presented adult midges, Forcipomyia sp. (subgen. Forcipomyia), Culicoides paraensis and Dasyhelea borgmeieri, with natural and synthetic cacao flower odors in choice assays. Midges showed weak attraction to the complete natural floral odor in the assay, with no significant evidence of interspecific differences. This suggests that cacao floral volatiles play a role in pollinator behavior. Midges were not attracted to a synthetic blend of the above four major components of cacao flower odor, indicating that a more complete blend is required for attraction. Our findings indicate that cacao pollination is likely facilitated by the volatile blend released by flowers, and that the system involves a generalized odor response common to different species of Ceratopogonidae

Prevalence of mitral annulus disjunction and mitral valve prolapse in a multicenter cohort of idiopathic ventricular fibrillation patients

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation Background Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with sudden onset of ventricular fibrillation of which the origin is not identified after extensive evaluations. Recent studies suggest an association between mitral annulus disjunction (MAD), mitral valve prolapse (MVP) and ventricular arrhythmias[1,2]. The prevalence of MAD and MVP in IVF patients in this regard, is not well established. Purpose To explore prevalence of MAD and MVP in IVF patients. Methods In this retrospective multicenter cohort study, Cardiac Magnetic Resonance images from IVF patients (i.e., negative for ischemia, cardiomyopathy and channelopathies) and matched control subjects were analyzed for MAD (≥2mm) and MVP (&amp;gt;2mm). Results In total, 71 IVF patients (mean age 39, 59% male) and 71 controls (mean age 41, 58% male) were included. MAD in the inferolateral wall was more prevalent in IVF patients versus healthy controls (6 [10%] vs. 1 [1%], p = 0.035). MVP was only seen in IVF patients and not in controls (4 [7%] vs. 0 [0%], p = 0.037). MVP was observed both in IVF patients with (n = 3) and without (n = 1) MAD. Patients with MAD did not show papillary muscle fibrosis. Four (67%) patients with MAD showed frequent ventricular ectopy from the basal myocardial region. Conclusion Inferolateral MAD and MVP were significantly more prevalent in IVF patients compared to healthy controls (figure). This is in line with previous studies suggesting a correlation between mitral valve disease and IVF. Our findings support further exploration of the pathophysiological mechanisms underlying a subset of IVF that associates with MAD and MVP. </jats:sec