Cardiopulmonary effects of Intralipid infusion in critically ill patients

Cardiopulmonary effects of 500 ml of 20% iv fat emulsion (Intralipid) infusion in two groups of patients who required mechanical ventilation were evaluated in our Critical Care Center. Group 1 included ten patients void of signs or symptoms of sepsis. Group 2 consisted of ten patients exhibiting clinical and laboratory signs and symptoms of sepsis. Data were measured before and immediately after Intralipid infusion and when serum lipemia cleared. Intralipid infusion precipitated a significant increase in venous admixture (Qsp/Qt) from 13.7 +/- 3.6 (SEM) to 18.0 +/- 6.5% and from 22.0 +/- 4.8 to 25.8 +/- 7.0% in groups 1 and 2, respectively. Mean pulmonary artery pressure (MPAP) increased from 22.7 +/- 4.2 to 29.2 +/- 8.1 mm Hg and 26.4 +/- 6.8 to 28.0 +/- 4.0 mm Hg in groups 1 and 2, respectively. When serum lipemia cleared, Qsp/Qt and MPAP returned to preinfusion levels. We conclude that Intralipid infusion increases pulmonary artery pressure and venous admixture in critically ill patients. These changes are temporary and coincidental with serum lipemia rather than presence or absence of sepsis. Adequate levels of oxygenation should be confirmed during Intralipid infusion in patients with borderline oxygenation.     

Effect of chronic altitude hypoxia on the behavior of the respiratory center. Study on normal subjects living at the altitude of Mexico City (2,240 meters)

Respiratory center (RC) output has been shown to be increased in hypoxemic Chronic Obstructive patients at sea level. In order to asses the separate role of chronic hypoxia on the RC output we studied 30 normal subjects all of them native and residents of Mexico City (altitude: 2,240 m, PaO2: 65-70 torr.). The parameters studied were: occlussion pressure (P0.1), mean inspiratory flow (Vi), and the ratio inspiratory time to total duration of the respiratory cycle (Ti/Ttot). The inspiratory impedance of the respiratory system as well as the minute ventilation (VE) and lastly to ensure isocapnic conditions, the end-tidal CO2 (PECO2), were also measured. These parameters were determined: 1) While breathing room air (RA), 2) after 30 min of breathing an inspired oxygen fraction (FiO2) of 30% and again 3) after 30 min of breathing and FiO2 of 100%. Fifteen of the subjects were studied on supine and the other 15 in the seated position. In most of the subjects the baseline (RA) values of P0.1 were found to be higher than those reported for normals at sea level. In every case, independent of body position, the P0.1 decreased (less than 0.01) to normal sea level values after 30 min of breathing O2 30%. Likewise, Vi and mechanical impedance also decreased (p less than 0.01) and no changes in Ti/Ttot were noted at this FiO2. No further changes occurred after breathing 100%. The above results show that: 1) The RC output in normal people at altitude (i.e. without mechanical abnormalities but with chronic hypoxia) is increased as compared to sea level.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comprehensive cooperative project for children with renal diseases in Nicaragua

In low-income countries renal diseases generally and chronic kidney disease (CKD) in particular represent a wide-spread and often underdiagnosed clinical problem. The aim of the cooperative project between the pediatric nephrology units of Milan, Italy, and Managua, Nicaragua was to improve the diagnosis and treatment of renal diseases and CKD in Nicaraguan children. When the project started, in 2000, there were many constraints in human and material resources in the Children's Hospital in Managua. Since 2001, a specialized Unit of Pediatric Nephrology and Urology has developed, offering free of charge basic clinical assistance to hospitalized children, and training abroad of the whole staff. Shared protocols, renovation of infrastructure and an information technology (IT) program were implemented. In 2003, renal replacement therapy (RRT) for selected children was initiated, along with a network of six department hospitals in 2005 and, in 2007, a CKD prevention program in the most peripheral Health Units, so that 61% of the Nicaraguan pediatric population is now covered by the project. To ensure implementation of the project, applications for funds to Italian private and public institutions were made and a Nicaraguan charity foundation was activated. The Nicaraguan Ministry of Health and the hospital directors were always involved in the plans of the development of the project and accepted the progressive transfer of the costs to the government, throughout the 9-year duration of the project. The IT program, inclusive of a database of children with kidney and other urinary tract (UT) diseases and a web connection between Milan and Managua, was crucial in monitoring the activities and providing epidemiological data, in order to better allocate resources. The clinical activities and the number of children managed in Managua in 2008 are similar to those of pediatric nephrology units worldwide and depict the level of clinical autonomy achieved. The sister-center model of cooperation and the top-down strategy we applied, along with the careful consideration of all the economic, logistic and political issues, were and are the key factors which explain the favorable results of this cooperative project.     

Aspectos actuales del síndrome de Sjögren: etiopatogenia,manifestaciones clínicas,diagnóstico y tratamiento

Sjögren's Syndrome (SS) is a chronic autoimmune disorder of the exbaocrine glands with associated lymphocytic infiltrates of the affected glands. SS occurs in a primary form not associated with other diseases and in a secondary form that complicates other rheumatic conditions. In both primary and secondary SS, decreased exocrine gland function leads to the “sicca complex”, a combination of dry eyes (xerophthalmia) and dry mouth (xerostomia). The clinical manifestations also include extraglandular disease features (skin, joints and muscles, lungs, kidneys, gastrointestinal tract). A variety of classification schemes have been proposed and discussed in the literature since the 1980s. The latest criteria, known as the American-European classification criteria for SS, were proposed in 2002. These criteria suggest that diagnosis of primary SS requires 4 of 6 criteria, including a positive minor-salivary biopsy sample and/or SS-A/SS-B antibodies. Therapy can be grouped into two separate aspects: treatment of dry eyes and dry mouth (replacement tears, muscarinic agonist agents…) and treatment of extraglandular manifestations (steroidal and non-steroidal anti-inflammatory agents, disease modifying agents, cytotoxic agents and biological therapies).     

Similar effects of roux-en-Y gastric bypass and vertical sleeve gastrectomy on glucose regulation in rats

Bariatric surgery is the most efficacious procedure for eliciting weight loss in humans, and many patients undergoing the procedure experience significant lessening of their symptoms of type-2 diabetes in addition to losing weight. We have adapted two bariatric surgical procedures commonly employed in humans to a rat model to begin to understand the mechanisms underlying the improvements in energy homeostasis. Young adult male rats received either roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG) and were assessed for body weight, food intake and parameters of glucose homeostasis over a 28-week period. Control rats received either a sham surgical procedure or else were unoperated. RYGB and VSG had comparable beneficial effects relative to controls. They ate less food and lost more weight, and they both had improved glucose parameters. The most intriguing aspect of the findings is that the two surgical procedures had such similar effects in spite of quite different rearrangements of the gastrointestinal system.     

Proteolytic cleavage of the voltage-gated Ca2+ channel alpha2delta subunit: structural and functional features

By mediating depolarization-induced Ca(2+) influx, high-voltage-activated Ca(2+) channels control a variety of cellular events. These heteromultimeric proteins are composed of an ion-conducting (alpha(1)) and three auxiliary (alpha(2)delta, beta and gamma) subunits. The alpha(2)delta subunit enhances the trafficking of the channel complex to the cell surface and increases channel open probability. To exert these effects, alpha(2)delta must undergo important post-translational modifications, including a proteolytic cleavage that separates the extracellular alpha(2) from its transmembrane delta domain. After this proteolysis both domains remain linked by disulfide bonds. In spite of its central role in determining the final conformation of the fully mature alpha(2)delta, almost nothing is known about the physiological implications of this structural modification. In the current report, by using site-directed mutagenesis, the proteolytic site of alpha(2)delta was mapped to amino acid residues Arg-941 and Val-946. Substitution of these residues renders the protein insensitive to proteolytic cleavage as evidenced by the lack of molecular weight shift upon treatment with a disulfide-reducing agent. Interestingly, these mutations significantly decreased whole-cell patch-clamp currents without affecting the voltage dependence or kinetics of the channels, suggesting a reduction in the number of channels targeted to the plasma membrane.     

Effect of short-term exposure to dichlorvos on synaptic plasticity of rat hippocampal slices: Involvement of acylpeptide hydrolase and α7 nicotinic receptors

Dichlorvos is the active molecule of the pro-drug metrifonate used to revert the cognitive deficits associated with Alzheimer's disease. A few years ago it was reported that dichlorvos inhibits the enzyme acylpeptide hydrolase at lower doses than those necessary to inhibit acetylcholinesterase to the same extent. Therefore, the aim of our investigation was to test the hypothesis that dichlorvos can enhance synaptic efficacy through a mechanism that involves acylpeptide hydrolase instead of acetylcholinesterase inhibition. We used long-term potentiation induced in rat hippocampal slices as a model of synaptic plasticity. Our results indicate that short-term exposures (20 min) to 50 μM dichlorvos enhance long-term potentiation in about 200% compared to the control condition. This effect is correlated with approximately 60% inhibition of acylpeptide hydrolase activity, whereas acetylcholinesterase activity remains unaffected. Paired-pulse facilitation and inhibition experiments indicate that dichlorvos does not have any presynaptic effect in the CA3 → CA1 pathway nor affect gabaergic interneurons. Interestingly, the application of 100 nM methyllicaconitine, an α₇ nicotinic receptor antagonist, blocked the enhancing effect of dichlorvos on long-term potentiation. These results indicate that under the exposure conditions described above, dichlorvos enhances long-term potentiation through a postsynaptic mechanism that involves (a) the inhibition of the enzyme acylpeptide hydrolase and (b) the modulation of α₇ nicotinic receptors.     

Val/Leu<Superscript>247</Superscript> and Trp/Ser<Superscript>316</Superscript> polymorphisms in β<Subscript>2</Subscript> glycoprotein I and their association with thrombosis in unselected Chilean patients

It is known that polymorphisms of β ₂-glycoprotein I (β ₂GPI) in exon 7 affect interaction between the phospholipid binding site and the antibodies, and that other polymorphisms in exon 8 increase the generation of antibodies. In this study, we analyzed genetic polymorphisms of β ₂GPI in unselected Chilean patients to determine the prevalence of β ₂GPI polymorphisms in the phospholipid domain in patients with venous and arterial thrombosis and the clinical correlation with thromboembolic complications. This study comprised 149 patients with venous and arterial thrombosis (62 with venous thrombosis and 87 with arterial thrombosis) and 160 healthy controls with no previous history of thrombosis. Polymorphisms of exons 7 and 8 of β ₂GPI, which encode for its fifth domain, were determined by PCR-RFLP. The presence of aPL or anti-β ₂GPI in the patients was detected by ELISA. Anti-β ₂GPI were present in 8/149 patients (5.4%); of these, five had aCL antibodies of low titer. The allele containing Val/Leu²⁴⁷ and Trp/Ser³¹⁶ was significantly more frequent in patients with thrombosis than in the control group (OR=3.1, CI 1.6–6.0, p=0.0003; OR=2.9, CI 1.1–8.6, p=0.027, respectively). These polymorphisms did not correlate with aPL or anti-β ₂GPI but significant differences were observed with venous thrombosis (p=<0.0001) and arterial thrombosis (p=0.026). In conclusion, the β ₂GPI polymorphisms Val/Leu²⁴⁷ and Trp/Ser³¹⁶ are not related to the presence of anti-β ₂GPI antibodies in unselected Chilean patients with venous and arterial thrombosis, but they are significantly associated with venous and arterial thrombosis.