Inhibitors of phosphoinositol 3 kinase and NFκB for the treatment of chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed. In the present article, we review the new patents on phosphoinositide 3 kinase and NFκb inhibitors for future therapies.     

Role of beta2 agonists in respiratory medicine with particular attention to novel patents and effects on endocrine system and immune response

Beta adrenergic receptors are very important in respiratory medicine. Traditionally, the stimulation of beta adrenergic receptors by beta2-agonists is commonly used for giving bronchodilation in chronic airflow obstruction However; the wide distribution of these receptors in cells and tissues other than airway smooth muscle suggests that beta agonists should offer other beneficial effects in respiratory disease. Recent studies have shown the importance of these receptors in the modulation of endocrine and immune system that affect respiratory function and may decrease therapy effectiveness in asthma and chronic obstructive pulmonary disease. New patented compound and uses have provided new insights in future therapeutics of respiratory diseases in which genetic, endocrine and immune response should be considered.     

Effect of antiphospholipid antibodies on the formation and lysis of fibrin network in patients with recurrent miscarriage

The present work was intended to study the process of fibrin formation and lysis and plasmin generation in a group of patients with recurrent miscarriage (RM), due to the presence of antiphospholipid antibodies (N = 10); as well as in women with RM without the antiphospholipid syndrome (APS) (N = 6), compared with those of a group of healthy women (N= 8). In the group of patients with APS, nine were positive for antibodies against cardiolipin (aCL), five for anti-beta2-glycoprotein I (anti-beta2GPI), four for both antibodies, and one for antibodies against prothrombin (aPT) and lupus anticoagulant (LA). Fibrin formation and lysis was followed by turbidity and plasmin generation using chromogenic substrate S2251. The polymerization curves from RM patients without APS and the LA patient showed an increased slope and maximum turbidity compared to those of the control group. The speed of lysis was higher in the LA patient (21 +/- 0) 10(-4) deltaOD/seg and the RM patients without APS (19.6 +/- 5.7) 10(-4) deltaDO/seg, compared to that of the control group (14.5 +/- 2.8) 10(-4) deltaDO/seg. Plasmin generation increased only in RM patients without APS (85 +/- 24%) against the control group (52 +/- 3%), p = 0.005. The changes observed in the fibrin polymerization and lysis process of women with RM without APS and LA seem to be related to their higher fibrinogen levels, while the increased plasmin generation was related to the patients' morbidity.     

Increasing crude and adjusted mortality rates for colorectal cancer in a developing South American country

Aim Colorectal cancer (CRC) is a major cause of cancer death worldwide. We examined temporal trends in death rates from colorectal cancer in Chile from 1983 to 2008. Method We analysed the mortality database in Chile from 1983 to 2008. Cases were selected using ICD‐9/10 codes. We calculated mortality rates per 100 000 inhabitants according to sex, age group and type of cancer – colon (CC) or rectal (RC). The rates were adjusted by a direct method using the WHO‐2000 standard population. Time trends were assessed with Prais–Winsten regression models. Results There were 26 250 deaths from CRC (75.7% for CC). There was a higher frequency of deaths from CC (57.6%) in women than in men, who had a higher frequency of deaths from RC (51.3%). The crude CC mortality rate increased by 116% (from 3.6 to 7.8), while the overall RC rate increased by 71% (from 1.4 to 2.4). After adjusting for age, a significant increase in mortality rate was found for CC (coefficient 0.09, 95% CI 0.08–0.11, P < 0.001) and RC (coefficient 0.02, 95% CI 0.009–0.04, P = 0.002) in men. In women, this increase was significant for CC (coefficient 0.03, 95% CI 0.005–0.05; P = 0.02), but not for RC (coefficient −0.007, 95% CI −0.02 to 0.005, P = 0.23). Conclusion The crude mortality rate from CRC has doubled in Chile in this period. After adjustment of mortality rates, it appears that much of this increase is due to the aging population. However, part of this increase could be explained by other factors.     

Klebsiella pneumoniae Increases the Levels of Toll-Like Receptors 2 and 4 in Human Airway Epithelial Cells

Airway epithelial cells act as the first barrier against pathogens. These cells recognize conserved structural motifs expressed by microbial pathogens via Toll-like receptors (TLRs) expressed on the surface. In contrast to the level of expression in lymphoid cells, the level of expression of TLR2 and TLR4 in airway epithelial cells is low under physiological conditions. Here we explored whether Klebsiella pneumoniae upregulates the expression of TLRs in human airway epithelial cells. We found that the expression of TLR2 and TLR4 by A549 cells and human primary airway cells was upregulated upon infection with K. pneumoniae. The increased expression of TLRs resulted in enhancement of the cellular response upon stimulation with Pam3CSK4 and lipopolysaccharide, which are TLR2 and TLR4 agonists, respectively. Klebsiella-dependent upregulation of TLR expression occurred via a positive IκBα-dependent NF-κΒ pathway and via negative p38 and p44/42 mitogen-activated protein kinase-dependent pathways. We showed that Klebsiella-induced TLR2 and TLR4 upregulation was dependent on TLR activation. An isogenic capsule polysaccharide (CPS) mutant did not increase TLR2 and TLR4 expression. Purified CPS upregulated TLR2 and TLR4 expression, and polymyxin B did not abrogate CPS-induced TLR upregulation. Although no proteins were detected in the CPS preparation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and colloidal gold staining, we could not rule out the possibility that traces of protein in our CPS preparation could have been responsible, at least in part, for the TLR upregulation.     

Bouveret's syndrome: new cause of double-arch-shadow sign in cholecystosonography

A case of Bouveret's syndrome which later presented as a jejunal obstruction is reported. Special reference is made to the echographic findings. Bouveret's syndrome has a double-arch-shadow image in the zone of the gallbladder bed on ultrasound examination. So far, this sign has been considered specific for gallstones inside the gallbladder.     

Anaphylactic reactions to suxamethonium (succinylcholine).

We present the case of a woman who had two severe anaphylactic episodes with hypotension and bradycardia in relation to the administration of general anesthesia. In the allergy evaluation, IgE antibodies to suxamethonium, a muscle relaxant which was used in both procedures, were detected by skin prick tests. No cross-reaction was found to other muscle relaxants derived from quaternary ammonium. The patient was able to be operated on, and did not present any adverse reactions to the use of local anesthesia or to general anesthesia using pancuronium as a muscle relaxant.     

Comparison of the results obtained through manual and automatic phonetogram

IntroductionThe phonetogram (F) is the graphic representation of a person phonatory potential. The F carried out with a sonometer and a frequency analyser is what is called “manual phonetogram” (MPh), and the one obtained by means of a computer is called the “automatic phonetogram” (APh).Material and methodsWe have carried out in 12 lyrical singers a standard MPh and an APh with the program Dr. Speech Science 3.0.ResultsIt was showed a significant difference with a p0,0005 in 14 of the 15 measures compared, and a p0,05 for the other one, being in general the results of the automatic test different from those of the manual in excess, with a correlation between the results obtained through both methods.ConclusionsThe APh obtained with the program Dr. Speech Science 3.0 is a faster and easier way to obtain the phonetogram than the one used to obtain the MPh, showing however big differences in excess compared with the ones of the MPh in all the usual phonetometric parameters.