3,4‐Dihydroxybenzaldehyde lowers ROS generation and protects human red blood cells from arsenic(III) induced oxidative damage

Arsenic (As) is a potent environmental toxicant and chronic exposure to it results in various malignancies in humans. Oxidative stress has been implicated in the etiopathogenesis of As‐induced toxicity. This investigated the protective effect of plant antioxidant 3,4‐dihydroxybenzaldehyde (DHB) on sodium meta‐arsenite (SA), an As‐(III) compound, induced oxidative damage in human red blood cells (RBC). The RBC were first incubated with different concentrations of DHB and then treated with SA at 37°C. Hemolysates were prepared and assayed for various biochemical parameters. Treatment of RBC with SA alone enhanced the generation of reactive oxygen species and increased lipid and protein oxidation. Reduced glutathione levels, total sulfhydryl content and cellular antioxidant power were significantly decreased in SA alone treated RBC, compared to the untreated control cells. This was accompanied by membrane damage, alterations in activities of antioxidant enzymes and deranged glucose metabolism. Incubation of RBC with DHB, prior to treatment with SA, significantly and dose‐dependently attenuated the SA‐induced changes in all these parameters. Scanning electron microscopy of RBC confirmed these biochemical results. Treatment of RBC with SA alone converted the biconcave discoids to echinocytes but the presence of DHB inhibited this conversion and the RBC retained their normal shape. These results show that DHB protects human RBC from SA‐induced oxidative damage, most probably due to its antioxidant character.     

Changes in potassium concentration and haematocrit associated with cardiopulmonary bypass in paediatric cardiac surgery

INTRODUCTION: A blood prime is frequently required for paediatric bypass surgery to maintain adequate haematocrit (Hct). However, stored blood can have high extracellular potassium levels and this study aims to investigate the effect of stored blood on the potassium concentration, both in the prime and subsequently in the patient after cardiopulmonary bypass (CPB) has been established. In neonatal surgery, the stored blood may be irradiated if there is a question of impaired immunity. Irradiation may cause a further increase in potassium levels. METHODS: Blood-primed circuits prepared for 320 consecutive paediatric bypass cases were analysed for electrolyte levels, Hct and acid-base status before and immediately after establishment of CPB. Patients were divided into three groups according to body weight (<5kg, 5-10kg and > 10 kg) and both stored blood and irradiated blood primes were compared. RESULTS: The potassium concentration was above the physiological range in all bypass primes pre-CPB and was significantly higher when using irradiated blood (8.12 +/- 2.54 mmol/L versus 4.94 +/- 3.35 mmol/L, p < 0.0001). Despite this, on commencing CPB, the potassium level remained within the physiological range in the majority of patients (4.16 +/- 2.72mmol/L for stored blood prime and 4.55 +/- 1.01mmol/L for irradiated blood, p = 0.02). However, in smaller patients (<5 kg) who had irradiated blood prime potassium level > 7.0 mmol/L, there was resultant hyperkalaemia (5.60 +/-0.90 mmol/L) on commencing CPB, that returned to normal later. No adverse clinical events were associated with the hyperkalaemia. Hct was well maintained on CPB (22-25%) in all groups and was not related to patient weight. CONCLUSION: Blood primes result in high potassium concentrations in the prime fluid that is more severe if irradiated blood is used. The concentration is not sufficient to cause hyperkalaemia in the patients on commencing CPB except when irradiated blood prime is used in infants < 5 kg. Hct is well maintained in all patient groups with the use of blood prime.     

Progesterone in transient ischemic stroke: a dose–response study

Rationale

Previous studies demonstrate the neuroprotective effects of progesterone in numerous animal injury models, but a systematic dose–response study in a transient ischemic stroke model is lacking.

Objectives

We investigated the effects of progesterone at different doses on post-stroke brain infarction and functional deficits in middle-aged rats.

Methods

Cerebral ischemia was induced in 13-month-old male Sprague–Dawley rats by right middle cerebral artery occlusion for 2 h followed by reperfusion. Rats received intraperitoneal injections of 8, 16, or 32 mg/kg of progesterone (P8, P16, P32) or vehicle at 2 h post-occlusion followed by subcutaneous injections at 6 h and every 24 h post-injury for 7 days. Functional recovery was evaluated at intervals over 22 days using motor, sensory, and cognitive tests. Infarct size was evaluated at 22 days post-stroke.

Results

Repeated-measures ANOVA showed significant group effects on grip strength, rotarod, and sensory neglect. All progesterone-treated groups had improved (p?p?Conclusions Although all doses were somewhat effective, progesterone given at 8 mg/kg led to the most consistent improvements across a panel of behavioral/functional tests and reduced the severity of ischemic infarct injury.     

Characteristics of Entrained Air Voids in Hardened Concrete with the Method of Digital Image Analysis Coupled with Schwartz-Saltykov Conversion

This paper presents the characteristics of air void systems in hardened concrete with the method of digital image analysis (DIA) coupled with Schwartz-Saltykov (SS) conversion. The results indicate that the DIA method coupled with SS conversion estimates the air content with more accuracy than it would without SS conversion; the correlation between air content obtained from the DIA method, and that from the thin section (TS) method is as good as the correlation observed between the pressure saturation (PS) method and the TS method. It was also found that the DIA method shows a better correlation with the TS method when the spacing factor without SS conversion is considered, while both methods show poor correlations when the corresponding specific surface is considered. In addition, it indicates that the peak of three-dimensional size distribution (3-DSD) of air voids after SS conversion falls in smaller voids, and 3-DSD of air voids shifts to a narrow size range, in comparison with the 2-DSD without SS conversion; the shape of the 3-DSD air voids remains constant irrespective of the class widths. Increasing the number of classes can minimise the standard deviation in the estimation, however, it also results in a leap in voids volume density, which will influence the estimation of air content.     

Survival of patients receiving fibrinolytic therapy for acute ST-segment elevation myocardial infarction in a developing country – patient characteristics and predictors of mortality

There is paucity of outcomes data on patients receiving fibrinolytic therapy (FT) for acute ST-elevation myocardial infarction (STEMI) in Indo-Asians. We conducted this study to determine survival as well as correlates of mortality in this population. Hospital charts of 230 patients receiving FT for acute STEMI between January 2002 and December 2004 were reviewed. Primary outcome variable was total mortality. Cox proportional hazards regression models were constructed. At a median follow-up of 717 days, 13.5% died, majority (23) during the in-hospital period. Multivariate predictors of mortality included (adjusted hazards ratio [HR], 95% confidence interval [CI]) age (HR 1.06, 95% CI 1.01–1.13), ejection fraction (HR 0.93, 95% CI 0.89–0.97), admission white cell count (HR 1.02, 95% CI 1.01–1.04) and change in ST-segment elevation (HR 0.96, 95% CI 0.92–0.99). We conclude that patients receiving FT for acute STEMI in Pakistan are a relatively high-risk group with a 10% in-hospital mortality and high frequency of recurrent events. Comparison data with primary angioplasty as an alternative strategy are needed.     

India’s first successful intestinal transplant: The road traveled and the lessons learnt

Intestinal transplant is a therapeutic challenge not just surgically but also logistically because of the multidisciplinary expertise and resources required. A large proportion of patients who undergo massive bowel resection and develop intestinal failure have poor outcome, because of inability to sustain long-term parenteral nutrition and limited availability of intestinal and multi-visceral transplantation facilities. We report the first successful isolated intestinal transplant from India.     

The use of ABO-incompatible grafts in living donor liver transplantation—First report from India

ABO incompatibility is the commonest reason for rejection of donors in living donor liver transplantation (LDLT). The donor pool could be expanded by 25 % to 35 % if the ABO barrier is overcome. In the absence of pre-conditioning, transplantation across the blood groups is fraught with the almost universal risk of antibody-mediated rejection (AMR) that rapidly leads to graft loss. However, AMR can be prevented by removal of preformed antibodies and reducing their production by B cells. We describe our initial experience of three cases of ABO-incompatible (ABO-i) LDLT: a 42-year-old male, an 8-month-old male and a 28-month-old female, all of blood group O+ who received blood group B + right lobe, B + left lateral segment, and A + left lateral segment liver grafts, respectively. Pre-LDLT conditioning included administration of anti-CD20 antibody (Rituximab^®) to the adult 4 weeks prior, and four to seven sessions of double-filtration plasmapheresis to all, to remove preformed antibodies and achieve anti-donor blood group antibody (ADA) titers of ≤1:16 IgG and ≤1:8 IgM, respectively. In addition, cases 1 and 3 received mycophenolate mofetil for 7 days prior to LDLT. After LDLT, all three patients achieved normal graft function over 8–17 days with no evidence of AMR and without the need for further plasmapheresis. Postoperative complications included portal vein thrombosis (one successfully re-explored), CMV (one), Pseudomonas and Klebsiella sepsis (one each), and abdominal collection (one treated with percutaneous drainage). All are currently well with normal graft function and low ADA titers at 8, 16, and 19 months after ABO-i LDLT.     

Regulation of iron homeostasis through the erythroferrone-hepcidin axis in sickle cell disease

Sickle cell disease (SCD) has a distinct pattern of transfusional iron overload (IO) when compared to transfusion-dependent β-thalassaemia major (TDT). We conducted a single institution prospective study to evaluate plasma biomarkers of iron regulation and inflammation in patients with SCD with IO (SCD IO cases, n = 22) and without IO (SCD non-IO cases, n = 11), and non-SCD controls (n = 13). Hepcidin was found to be inappropriately low, as evidenced by a significantly higher median hepcidin/ferritin ratio in non-SCD controls compared to SCD IO cases (0·3 vs. 0·02, P < 0·0001) and SCD non-IO cases (0·3 vs. 0·02, P < 0·0001), suggesting that certain inhibitory mechanism (s) work to suppress hepcidin in SCD. As opposed to the SCD non-IO state, where hepcidin shows a strong significant positive correlation with ferritin (Spearman ρ = 0·7, P = 0·02), this correlation was lost when IO occurs (Spearman ρ = −0·2, P = 0·4). Although a direct non-linear correlation between erythroferrone (ERFE) and hepcidin did not reach statistical significance both in the IO (Spearman ρ = −0·4, P = 0·08) and non-IO state (Spearman ρ = −0·6, P = 0·07), patients with highest ERFE had low hepcidin levels, suggesting that ERFE contributes to hepcidin regulation in some patients. Our results suggest a multifactorial mechanism of hepcidin regulation in SCD.