Protective effect of dexmedetomidine against organ dysfunction in a two-hit model of hemorrhage/resuscitation and endotoxemia in rats

Dexmedetomidine (DEX), a selective agonist of α2-adrenergic receptors, has anti-inflammation properties and potential beneficial effects against trauma, shock, or infection. Therefore, this study aimed to investigate whether DEX might protect against multiple-organ dysfunction in a two-hit model of hemorrhage/resuscitation (HS) and subsequent endotoxemia. Eighty Wistar rats were randomized into four groups: NS (normal saline), HS/L (HS plus lipopolysaccharide), HS/L+D (HS/L plus dexmedetomidine), and HS/L+D+Y (HS/L+D plus yohimbine). Six hours after resuscitation, blood gas (PaO2) and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urine nitrogen (BUN), creatinine (Cr), TNF-α, IL-β, IL-6, IL-8, IL-10, and nitric oxide (NO) were measured. The histopathology was assayed by staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) were assayed. The PaO2 levels in HS/L rats were lower whereas the ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, IL-10, and NO levels were higher compared to the control group. The HS/L+D increased PaO2 and further increased IL-10 and decreased ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, and NO levels of the HS/L groups. In addition, the MDA in the HS/L groups increased whereas SOD activity decreased compared to the control group. Moreover, the HO-1 expression levels were increased by DEX administration in lung, liver, and kidney tissues. Lungs, livers, and kidneys of the HS/L group displayed significant damage, but such damage was attenuated in the HS/L+D group. All of the above-mentioned effects of DEX were partly reversed by yohimbine. DEX reduced multiple organ injury caused by HS/L in rats, which may be mediated, at least in part, by α2-adrenergic receptors.

The effect of polymorphism of the beta-2 adrenergic receptor on the response to beta-2 agonist in bronchial asthma patients.

AIM: To discover the role of beta2-adrenergic receptor (beta2-AR) polymorphism on the response to beta-2 agonist, particularly in coding amino acid at sequences 16 and 27 as well as adjacent nucleotides. METHODS: The study was conducted by nested case-control method with consecutive samples of asthma patients aged 15-60 years at the outpatient clinic, Department of Pulmonology in Dr. Wahidin Sudirohusodo General Hospital, Makassar. Twenty-eight patients were found irresponsive to terbutaline nebulation (increased FEV1 < 15%) and 56 patients were responsive (increased FEV1 > or =15%). DNA extraction and amplification were performed by PCR as well as polymorphism detection, which was done by automatic sequencing machine. RESULTS: The Arg 16 polymorphism did not have any effect on the response to terbutaline nebulation, but Gln 27 polymorphism did with OR 3.18. New polymorphism was found in nucleotide at 20th order before the start codon, it was T/C -20, which also has an effect on the response to terbutaline nebulation with OR 4.53. When the three polymorphisms were combined, the effect were greater with OR 11.11. It was found that age, gender, obesity, onset and ethnicity had no effect on the response to terbutaline nebulation. CONCLUSION: Polymorphism of the novel Gln 27 and T/C -20 (newly known) have an effect on the response to beta-2 agonist. Both combination and polymorphism of Arg 16 will bring greater effect on the response to beta-2 agonist.

Ion channels: new targets for the next generation of tocolytics agents.

Ion channels are interesting molecules since they mediate not only uterine contraction but also uterine relaxation. We have examined the expression, function, and correlation between the large conductance calcium-activated potassium (BKCa) channel, beta2 adrenoceptor (AR), and long-lasting (L) type calcium (Ca2+) channel. These are the main channels and receptor that are involved in the uterine contraction/ relaxation process. Our evidence has shown that BKCa channel is closely correlated with beta2 AR in mediating uterine relaxation. Both proteins are situated in close proximity on the plasma membrane of human myometrium and are downregulated approximately 50% after the onset of labor. Interestingly, L type Ca2+ channel, which involves in the contraction pathway, seems to be in the same compartmentation as BKCa channel/ beta2 AR macromolecular complex. Further studies are now being conducted to identify the signaling complex components that could potentially be a target for new tocolytic agents.

Status of inhalation therapy in bronchial asthma in adults above twelve years of age in armed forces.

OBJECTIVE: The aim of this study was to evaluate the status of inhalation therapy in bronchial asthma in terms of frequency of its use, role of general physicians and general practitioners in prescribing inhalation therapy, role of inhaled steroids and B2 agonists, concurrent use of oral drugs, technique of using inhaler devices, use of spacer devices and peak flow monitoring. MATERIAL AND METHODS: 150 patients (76 males, 74 females) of bronchial asthma over 12 years of age referred to chest clinic of a tertiary care hospital for inadequate control were interviewed on the basis of a questionnaire and screening of prescription and case records wherever available. RESULTS: 127 (84.6%) patients were on inhalation therapy and maximum number of prescriptions was by general physicians (81%). The dosages of inhaled steroids were less than 400 mg in 60 (83.3%) cases and 26 (36%) patients discontinued it after some time. All patients were on beta-2 agonist inhalers and 74 (58.3%) patients were using these on regular basis. The concurrent use of oral short acting B2 agonist and oral steroids was seen in 107 (84%) and 41 (32.2%) patients respectively. Metered dose inhalers (MDIs) were most frequently used inhaler devices in 100 (78.7%) cases followed by rotahalers in 27 (21%) cases. The technique of using MDI and rotahalers was incorrect in 64 (64%) and 7 (25.9%) cases respectively. Spacer devices were used rarely and none of the patients were monitored by peak flow rates. CONCLUSIONS: Although inhalation therapy was being prescribed in large number of patients, more so by general physicians, yet the therapy was not being effective considering the fact that the referral to chest clinic in all the cases was for uncontrolled asthma. The main reasons for ineffective inhalation therapy were, underuse of inhaled steroids, overuse of B2 agonists and incorrect use of inhaler devices. There is an urgent need to educate general physicians especially in regards to usefulness of inhaled steroids, as on demand use of B2 agonists, demonstration of correct inhalation technique to patients, use of spaces devices and peak flow monitoring.