Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean section: a Cochrane systematic review

Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia for elective caesarean section, but it is not clear if one is better than the other. The primary objective of this systematic review was to determine the effectiveness and safety of hyperbaric bupivacaine compared with isobaric bupivacaine administered during spinal anaesthesia for elective caesarean section. We included 10 studies with 614 subjects in the analysis. There was no evidence of differences either in the risk of conversion to general anaesthesia, with a relative risk (95%CI) of 0.33 (0.09–1.17) (very low quality of evidence), or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61 (0.26–1.41) (very low quality of evidence). There was also no evidence of a difference in the use of ephedrine, the amount of ephedrine used, nausea and vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory block height of T4, with a mean difference (95%CI) of ?1.06 min (?1.80 to ?0.31). Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and spinal technique used, future clinical trials should look into using adequate sample size to investigate the primary outcome of the need for supplemental analgesia.     

Mediation of swim-stress antinociception by the opioid delta 2 receptor in the mouse.

The present study has characterized the antinociceptive response to cold water swim-stress (CWSS) in mice using opioid-selective antagonists as well as tolerance and cross-tolerance approaches. Mice subjected to CWSS using water at 5 degrees C for 3 min showed a marked antinociceptive response in the tail-flick test, which reached approximately 90% after +10 min, and which persisted for 15 to 20 min. This antinociceptive response (at +10 min) was antagonized by naloxone or by the delta antagonist ICI 174,864. Additionally, the CWSS response was antagonized by the opioid delta 2 antagonist, naltrindole-5'-isothiocyanate, but not by the delta 1 antagonist, [D-Ala2,Leu5,Cys6]enkephalin, or by the mu antagonist, beta-funaltrexamine or by the kappa antagonist, norbinaltorphimine. Although the CWSS-induced antinociceptive effect was blocked by some delta antagonists and tolerance resulted from the CWSS-induced response, the decrease in body temperature after each CWSS exposure was not affected by the opioid antagonists and reliably occurred in CWSS-tolerant mice, suggesting that the observed antinociception was independent of changes in body temperature. In mice rendered tolerant to the antinociceptive actions of the mu agonist, [D-Ala2,NMPhe4,Gly-ol] enkephalin, or to [D-Pen2,D-Pen5]enkephalin (predominantly a delta 1 agonist), the CWSS-induced antinociceptive response was unaltered. In contrast, in mice tolerant to the delta 2 agonist, [D-Ala2,Glu4]deltorphin, the CWSS-induced antinociceptive response was markedly and significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers

Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti‐IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free‐breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre‐clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra‐short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti‐IL4Rα‐conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers’ colocalizations with the inflammatory sites in the lung of ovalbumin‐challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd.     

The Bath Ankylosing Spondylitis Activity and Function Indices (BASDAI and BASFI) and their correlation with main symptoms experienced by patients with spondyloarthritis

With the aim of assessing whether the Bath Ankylosing Spondylitis Activity and Function Indices (BASDAI and BASFI) are reliable measures of disease activity and function in patients with spondyloarthritides (SpAs), 341 patients with SpA (representing ankylosing spondylitis (14.5%), psoriatic arthritis (27.3%), enteropathic arthritis (6.3%), reactive arthritis (4.9%), and undifferentiated arthritis (46.5%) were asked to complete the BASDAI and BASFI. They were asked to report what their main problems associated with the disease were from a list of seven symptoms: fatigue, neck pain, upper back pain, lower back pain, stiffness, joint pain or swelling, and pain with pressure on joints. Correlations between the main symptoms experienced by patients with SpAs and the indices, defined by Spearman’s correlation coefficient, showed that BASDAI best correlated with neck pain [BASDAI 2 and total BASDAI score correlate strongly (p = 0.003 and 0.001, respectively), and BASDAI 1, 4, and 5 correlate moderately (p = 0.03, 0.02, and 0.01, respectively)], followed by stiffness, upper back pain, pain with pressure, lower back pain, fatigue, and joint pain. Stiffness correlated strongly with nine of ten items on BASFI (BASFI 1 showed moderate correlation, p = 0.01), followed by upper back pain (four of ten items correlated strongly, three of ten correlated moderately), neck pain (three of ten tasks correlated strongly and four of ten correlated moderately), lower back pain (one task correlated strongly, five moderately), joint pain and swelling (four tasks correlated moderately), fatigue (three tasks correlated moderately), and pain with pressure (two tasks correlated moderately). BASDAI and BASFI only partly reflect disease activity and patients’ functional capacity in SpAs. An alternate instrument is required to assess SpA disease activity and functional capacity more precisely.     

Maternal sociodemographic characteristics and risk factors of antepartum fetal death

The objectives of this study were to assess the sociodemographic profile and to identify the risk factors of ante-partum fetal death which occurs after the age of viability of fetus. This prospective observational study was conducted in the Obstetrics department of Ad-din Women Medical College Hospital during the period of June, 2009 to July, 2010. A total of 14,015 pregnant patients were admitted in the study place after the age of viability, which was taken as 28 weeks of gestation for our facilities. Eighty-three (0.59%) of them were identified as intrauterine fetal death. Assessment of maternal sociodemographic characteristics and maternal-fetal risk factors were evaluated with a semi structured questionnaire pretested. Majority (81.92%, n=68) of the patients were below 30 years of age, 78.31% belonged to middle socioeconomic group. Almost 58% women had education below SSC level and 28.91% took regular antenatal checkup. About 61.45% patients were multigravida. Most (59.04%) ante-partum deaths were identified below 32 weeks of pregnancy. Out of 83 patients, maternal risk factors were identified in 41(49.59%) cases where fetal risk factors were found in 16(19.27%) cases; no risk factors could be determined in rests. Hypertension (48.78%), diabetes (21.95%), hyperpyrexia (17.3%), abruptio placentae (4.88%) and UTI (7.36%) were identified as maternal factors; and congenital anomaly (37.5%), Rh incompatibility (37.5%), multiple pregnancy (12.5%) and post-maturity (12.5%) were the fetal risk factors. Here, proximal biological risk factors are most important in ante-partum fetal deaths. More investigations and facilities are needed to explain the causes of antepartum deaths.     

Cigarette smoke induces p-benzoquinone-albumin adduct in blood serum: Implications on structure and ligand binding properties

Earlier we had reported that irrespective of the source cigarette smoke (CS) contains substantial amounts of p-benzosemiquinone, which is readily converted to p-benzoquinone (p-BQ) by disproportionation and oxidation by transition metal containing proteins. Here we show that after CS-exposure, p-BQ-protein adducts are formed in the lungs as well as serum albumin of guinea pigs. We also show that serum of human smokers contains p-BQ-albumin adduct. It is known that human serum albumin (HSA) plays a very important role in binding and transport of a variety of ligands, including fatty acids and drugs. We show in vitro that p-BQ forms covalent adducts with free amino groups of all twenty amino acids as well as ?-amino groups of lysine residues of HSA in a concentration dependent manner. When HSA is incubated with p-BQ in the molar ratio of 1:1, the number of p-BQ incorporated is 1. At the molar ratio of 1:60, the number of p-BQ incorporated is 40. The formation of HSA-p-BQ adduct has been demonstrated by absorption spectroscopy, MALDI-MS and MALDI-TOF-TOF-MS analyses. Upon complexation with p-BQ, the secondary structure and conformation of HSA are altered, as evidenced by steady state and time-resolved fluorescence, circular dichroism, 8-anilino-1-napthalenesulfonic acid binding and differential scanning calorimetry. Alteration of the structure and conformation of HSA results in impairment of its ligand binding properties with respect to myristic acid, quercitin and paracetamol. This might be one of the reasons why transport and distribution of lipids and drugs are impaired in smokers.     

Oxidative stress and toxicity induced by the nucleoside reverse transcriptase inhibitor (NRTI)--2',3'-dideoxycytidine (ddC): relevance to HIV-dementia

Human immunodeficiency virus dementia (HIVD) is the most common form of dementia occurring among young adults. In HIVD, neuronal cell loss occurs in the absence of neuronal infection. With the advent of highly active anti-retroviral therapy (HAART), the incidence of HIVD has drastically reduced, though prevalence of milder forms of HIVD continues to rise. Though these agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. Here we examine the possible role of NRTIs, in particular 2',3'-dideoxycytidine (ddC), in the neuropathology of HIVD. Synaptosomes and isolated mitochondria treated and incubated for 6 h with CSF-achievable concentrations of ddC, i.e., 6-11 ng/ml, were found to show a significant increase in oxidative stress with 40 nM ddC as measured by protein carbonyls and 3-nitrotyrosine (3NT), effects that were not observed in the more tolerable NRTI, 3TC. Protection against protein oxidation induced by ddC was observed when brain mitochondria were isolated from gerbils 1 h after injection i.p. with the brain accessible antioxidant and glutathione mimetic, tricyclodecan-9-yl-xanthogenate (D609). In addition, there is a significant reduction in the levels of anti-apoptotic protein Bcl-2 and a significant increase in cytochrome c release and also a significant increase in the expression of pro-apoptotic protein caspase-3 after mitochondria were treated with 40 nM ddC. The results reported here show that ddC at 40 nM can induce oxidative stress, cause the release of cytochrome c, and in addition, reduce the levels of anti-apoptotic proteins, increase the levels of pro-apoptotic proteins, thereby increasing the possibility for induction of apoptosis. These findings are consistent with the notion of a possible role of the NRTIs, and in particular, ddC, in the mechanisms involved in HIVD.