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Carney complex (CNC) is an autosomal dominantly inherited syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxoma, and endocrine overactivity. Skin pigmentation includes lentigines and blue nevi. Myxomas may occur in breast, skin and heart. Cardiac myxomas may be multiple and occur in any cardiac chamber, and are more prone to recurrence. The most common endocrine gland manifestation is an ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD may occur isolated, with no other signs of CNC. Pituitary and thyroid glands and gonads are also involved. The PRKAR1A gene, located in 17 q22-24, encodes type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of patients with CNC. PRKAR1A is a key component of the c-AMP signaling pathway that has been implicated in endocrine tumorigenesis. Many different mutations have been reported in the PRKAR1A gene. In almost all cases the sequence change was predicted to lead to a premature stop codon and the resultant mutant mRNA was subject to nonsense-mediated mRNA decay. There is no clear genotype-phenotype correlation in patients with CNC. Genetic analysis should be performed in all CNC index cases. All affected patients should be monitored for clinical signs of CNC at least once a year. Genetic diagnosis allows for more effective preparation of more appropriate and effective therapeutic strategies and genetic counseling for patients and gene carriers, and to avoid unnecessary tests to relatives not carrying the gene., (Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.)

Tadalafil, which was commercialized in 2009, is a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, and may be a safe and effective therapeutic alternative for patients with class II and III pulmonary hypertension (PH) in the World Health Organization's classification--as stated in the Clinical Practice Guidelines for the Diagnosis and Treatment of PH of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)--providing benefits in exercise tolerance, delaying clinical deterioration and improving quality of life. Given the greater half-life of this drug, allowing a single oral dose of 40 mg per day, tadalafil could improve therapeutic compliance--thus facilitating treatment adherence--among patients with PH., (Copyright © 2011 Sociedad Española de Neumología y Cirugía Torácica. Published by Elsevier Espana. All rights reserved.)

Aims: To review the role played by the mitochondrial permeability transition pore (MPTP) in different physiological and pathological processes., Method: Both genetic and functional alterations in mitochondria can lead to errors that trigger programmed cell death, which in turn give rise to a number of diseases that affect the nervous system. Over the last few years the mitochondrion has been seen as the link between the different signalling pathways involved in some degenerative processes. The mitochondrion seems to play an important part in the cellular decision making that leads, irreversibly, toward the execution phase in cellular death processes. This being the case, the action would be mediated by the permeability of its membranes, through the formation of the mitochondrial permeability transition pore, and would involve phenomena such as the dissipation of the mitochondrial electrochemical potential and the release of substances from within it. These substances include apoptosis inducing factor (AIF), apoptosis protease activating factor 1 (apaf 1), cytochrome c and members of the protease family: the caspases. These alterations have been described in neurodegenerative pathologies such as Alzheimer s and Parkinson s disease, amyotrophic lateral sclerosis and transmissible spongiform encephalopaties., Conclusions: Designing pharmaceutical products capable of interfering with the functions of MPTP would allow a better therapeutic approach in neurological pathologies.

Introduction: Numerous observations indicate that, while the predominant clinical expression arises from brain pathology, Alzheimer s disease (AD) has systemic expression at the cellular and molecular levels. Although these alterations seem to be inconsequential outside the central nervous system, their parallel expression in the brain could be considered a plausible pathophysiological model and explain part of the clinical manifestations; in particular those related to memory loss., Development: Recent research has provided experimental evidence of a direct or indirect linkage between alteration in ion channels, PKC, calcium homeostasis and amyloid processing in peripheral tissues. Some evidence also indicates similar phenomena in the brain, attesting to the relevance of the changes in non CNS cells., Conclusion: Considering the difficulties of using post mortem material to study dynamic and/or early event in mostly end stage, disease ridden tissues, peripheral cells such as fibroblasts offer a model to study cellular aspects of AD pathophysiology.

In recent years, nitric oxide (NO), a single but highly reactive molecule has become known as the central point of many researchs. NO is synthesized by the enzyme nitric oxide synthase (NOS) in mammals from the amino-acid L-arginine. The products of L-arginine oxidation by NOS are L-citrulline and NO. Nitric oxide has a very short half life, is lipid soluble, reacts easily with several enzymatic systems, and is produced by a wide amount of cells. At least, three kinds of enzymes NOS have been described: two of them are calcium-dependent and continuously present in select cells (constitutive NOS, cNOS). One cNOS isoform is present in the cytosol of neuronal cells, while the other isoform is present in membrane-bound form, in endothelial cells. cNOS produces small quantities of NO, following stimulation by specific agonist. NO produced by cNOS frequently mediates cellular communications and cellular signaling. A third isoform is calcium-independent, is not present in unstimulated cells, and produces large quantities of NO following stimulation of the appropriate cell with cytokines or LPS (inducible NOS, iNOS). NO is a mediator of both physiological and pathological process. It acts directly on its targets, one of them, maybe the most important, is the soluble guanylate cyclase, and produces a variety of biological effects, ranged from cytoprotection to cytotoxicity. An analysis of the biochemistry and physiology of NO is the focus of this review, together with its biological action and potential therapeutical implications.

The supernatant fluid of axenically grown E. histolytica contains a factor (MLIF) which inhibits the locomotion of human monocytes (including chemotaxis) without affecting that of human polymorphonuclear leucocytes. Locomotion, like other cellular functions, is modulated by changes in intracellular cAMP and cGMP. The consensus--with some exceptions--is that while rises in cGMP accompany locomotion, an increase in cAMP (without a concomitant fall in -cGMP) occurs with inhibition of cellular movement. We measured by radioimmunoassay the cAMP concentration of human monocytes exposed to inhibitory concentrations of MLIF. A significant (p less than 0.005) rise in monocyte cAMP was found, comparable to that observed with the use of forskolin, a well known cAMP stimulator. The control studies using plain axenic medium, not only failed to reveal any rise in cAMP but disclosed a small, yet not significant drop in intracellular cAMP. These results suggest that MLIF (like other locomotion inhibitors, i.e. prostaglandins E1, A1 and isoproterenol) produces a significant increase in intracellular monocyte cAMP. This modification in intracellular signals may contribute to the inhibition in monocyte locomotion, an event during which an increase in pericentriolar microtubules has also been observed.

The intracellular messengers that seem to be involved in renin secretion (RS) from juxtaglomerular cells (JG) are calcium (Ca), cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Unlike the majority of secretory systems, an increase in intracellular Ca concentration and calmodulin and protein kinase C activation inhibit RS. The intracellular Ca concentration in JG cells can be modified if: 1) the normal mechanisms of Ca extrusion of these cells is altered; 2) the calcium output is blocked by lanthanum; 3) the function of the voltage-sensitive Ca-channels is modified; 4) uptake or liberation of Ca from endoplasmic reticulum is modified; 5) plasmatic membrane is bypassed with calcium ionophores such as A 23187. 6) JG cells are stimulated by hormones that increase Ca and activate protein kinase C such as angiotensin II, vasopressin or alpha-1 adrenergic agonists; 7) extracellular Ca concentration increases or decreases. RS is stimulated by dibutyryl cAMP, cAMP phosphodiesterase inhibitors and by hormones and agents that activate adenylate cyclase (beta adrenergic agonists, bradykinin, histamine, forskolin and ethylcarboxamide adenosine). On the contrary, RS is inhibited by hormones and agents that inhibit adenylate cyclase such as: alpha-2 adrenergic agonists, neuropeptide Y, angiotensin II and cyclohexyladenosine. Pertussis toxin increases basal RS, blocks the inhibition by agents and hormones which inhibit adenylate cyclase and potentiate the stimulation produced by beta-adrenergic agonists. In JG cells, atrial natriuretic peptide inhibits RS, increases cGMP and decreases cAMP. The increase in cGMP correlates well with the inhibition of RS.