Contrasting actions of diesel exhaust particles on the pulmonary and cardiovascular systems and the effects of thymoquinone

BACKGROUND AND PURPOSE: Acute exposure to particulate air pollution has been linked to acute cardiopulmonary events, but the underlying mechanisms are uncertain. EXPERIMENTAL APPROACH We investigated the acute (at 4 and 18 h) effects of diesel exhaust particles (DEP) on cardiopulmonary parameters in mice and the protective effect of thymoquinone, a constituent of Nigella sativa. Mice were given, intratracheally, either saline (control) or DEP (30 μg·per mouse). KEY RESULTS At 18 h (but not 4 h) after giving DEP, there was lung inflammation and loss of lung function. At both 4 and 18 h, DEP caused systemic inflammation characterized by leucocytosis, increased IL-6 concentrations and reduced systolic blood pressure (SBP). Superoxide dismutase (SOD) activity was decreased only at 18 h. DEP reduced platelet numbers and aggravated in vivo thrombosis in pial arterioles. In vitro, addition of DEP (0.1-1 μg·mL(-1)) to untreated blood-induced platelet aggregation. Pretreatment of mice with thymoquinone prevented DEP-induced decrease of SBP and leucocytosis, increased IL-6 concentration and decreased plasma SOD activity. Thymoquinone also prevented the decrease in platelet numbers and the prothrombotic events but not platelet aggregation in vitro. CONCLUSIONS AND IMPLICATIONS: At 4 h after DEP exposure, the cardiovascular changes did not appear to result from pulmonary inflammation but possibly from the entry of DEP and/or their associated components into blood. However, at 18 h, DEP induced significant changes in pulmonary and cardiovascular functions along with lung inflammation. Pretreatment with thymoquinone prevented DEP-induced cardiovascular changes.     

Bullet and Blast ENT Injuries in Counter-Insurgency Area

Background

Many ENT injuries are not recognized easily, but they have the potential of increasing the morbidity.

Methods

ENT injuries managed in two tertiary care Level-IV hospitals between 2006 and 2007 were studied with a view to formulate strategy in efficient management of these cases.

Result

Emergency bags did not carry readymade packs to control nasal bleeds. Routinely screening of ears in all blast injury cases in the ‘Blast Injury Program’ helped in early identification of hearing loss. Lack of sufficient stenting of nasal cavities resulted in severe nasal stenosis which was difficult to repair. Splinters lodged in pharyngeal wall escaped detection, resulting in concealed haemorrhage and shock.

Conclusion

Nasal packs and epistaxis catheters must be included in emergency bags to minimize blood loss at first contact. Screening for ear trauma in all blast injuries increases detection rate and is beneficial to the soldier. Stenting of injured nasal cavities and early transfer to a tertiary care hospital could reduce morbidity. Plain radiography of head and neck areas could help detect splinters in vital areas and guide management.Key Words: Combat injuries ENT, Blast injuries ear     

Impact of Endoscopic Sinus Surgery on Symptom Manifestation of Chronic Rhinosinusitis

Background

Rhinosinusitis is a significant health problem which results in large financial burden on society. The study evaluated the prevalence and severity of individual symptoms of chronic rhinosinusitis (CRS) and the impact of endoscopic sinus surgery (ESS) on the symptoms and medication used in patients with CRS.

Methods

Patients with refractory CRS were assessed prospectively with ESS intervention. We studied the symptoms, change in medical therapy, complications of surgery and effect of other factors like smoking, polyposis and asthma on endoscopy and computed tomography scan scores.

Result

A total of 81 patients underwent ESS for CRS. Post nasal drip (95%), headache (91%), nasal discharge (90%) and nasal obstruction (86%) were the commonest symptoms. Postoperatively, the highest improvement was seen in nasal blockage (87.2%), postnasal drip (84.4%) and headache (82.4%). Endoscopy scores were significantly worse in patients with polyps, asthma and smoking. A significant reduction in use of antibiotic and antihistaminics was seen post surgery. Seven patients who had extensive polyposis preoperatively, had recurrence and required revision surgery. Nasal synechiae formation and mild bleeding were the minor complications.

Conclusion

Endoscopic sinus surgery results in significant improvement in the symptoms of patients with CRS alongwith a definitive decrease in antibiotic and antihistaminic requirement. We conclude that ESS is an effective treatment for CRS in those who fail to respond to medical treatment.Key Words: Chronic rhinosinusitis, Endoscopic sinus surgery     

Slow wave propagation and plasticity of interstitial cells of Cajal in the small intestine of diabetic rats

The number of myenteric interstitial cells of Cajal (ICC-MY), responsible for the generation and propagation of the slow wave in the small intestine, has been shown to decrease in diabetes, suggesting impairment of slow-wave (SW) propagation and related motility. To date, however, this expected decrease in SW propagation has neither been recorded nor analysed. Eleven rats were treated with streptozotocin and housed in pairs with 11 age-matched control animals. After 3 or 7 months, segments of duodenum, jejunum and ileum were isolated and divided into two parts. One part was processed for immediate freezing, cryosectioning and immunoprobing using anti-c-Kit antibody to quantify ICC-MY. The second part was superfused in a tissue bath, and SW propagation was recorded with 121 extracellular electrodes. In addition, a cellular automaton was developed to study the effects of increasing the number of inactive cells on overall propagation. The number of ICC-MY was significantly reduced after 3 months of diabetes, but rebounded to control levels after 7 months of diabetes. Slow-wave frequencies, velocities and extracellular amplitudes were unchanged at any stage of diabetes. The cellular automaton showed that SW velocity was not linearly related to the number of inactive cells. The depletion of ICC-MY is not as severe as is often assumed and in fact may rebound after some time. In addition, at least in the streptozotocin model, the initial reduction in ICC-MY is not enough to affect SW propagation. Diabetic intestinal dysfunction may therefore be more affected by impairments of other systems, such as the enteric system or the muscle cells.     

Evaluation of interleukin-6, tumour necrosis factor-α and interleukin-1β for early diagnosis of neonatal sepsis

The objective of this study was to assess the contribution of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) to an early diagnosis of early-onset neonatal sepsis. A cohort of 117 newborn infants delivered during a 1-y period had IL-6, TNF-alpha and IL-1beta, blood and cerebrospinal fluid (CSF) cultures, leucocyte and platelet count collected on the initial evaluation of possible early-onset sepsis. They were divided into four groups: I, positive blood and/or CSF cultures; II, probably infected with clinical sepsis but negative cultures; III, same as group II but mother received antibiotic antepartum; and IV, newborn infants that did not receive any antibiotic therapy. There were no differences among the four groups with respect to mean gestational ages and birthweights, median Apgar scores, type of delivery, or number of newborn infants with leucocyte count <5000 mm(-3) or >25000 mm(-3), platelet count <100000 mm(-3), immature/total neutrophil ratio >0.2, absolute neutrophil count <1000mm(-3) and median IL-1beta levels. Median IL-6 and TNF-alpha levels were significantly higher in groups with patients with a diagnosis of clinical sepsis than in controls. The optimal cut-off point was 32 pg ml(-1) for IL-6 and 12 pg ml(-1) for TNF-alpha. The combination of both provided a sensitivity of 98.5%. In conclusion, the combination of IL-6 and TNF-alpha is a highly sensitive marker of sepsis in the immediate postnatal period.     

Diet, plasma lipoproteins and experimental atherosclerosis in baboons (Papio sp.)

Diet-induced hyperlipidaemia in baboons is similar to that inhumans. As in humans, the ratio between low density lipoprotein(LDL) and high density lipoprotein (HDL) cholesterol is a majordeterminant of atherosclerosis. Baboons, like humans and othernon-human primates, vary in their lipaemic responses to dietarylipids. By selective breeding based on variability in plasmaand lipoprotein cholesterol response to diet, lines of baboonswith high and low responses of various lipoproteins have beendeveloped. Genetic analyses suggest that lipoprotein patternsin responses to dietary cholesterol and fat are heritable. Metabolicand molecular studies of high and low LDL and HDL cholesterolresponses to dietary lipids have suggested that different mechanismsregulate plasma LDL cholesterol on the chow and on the highcholesterol-high fat (HCHF) diet. On the chow diet, plasma LDLcholesterol levels are positively associated with cholesterolabsorption and negatively associated with hepatic LDL receptorlevels and, thus, cholesterol absorption and LDL receptors seemto regulate plasma LDL cholesterol levels. However, when theanimals consume a human-like fat- and cholesterol-enriched diet,plasma LDL cholesterol levels are not associated with eithercholesterol absorption or hepatic LDL receptor mRNA levels,but are negatively associated with plasma 27-hydroxycholesterolconcentrations, hepatic sterol 27-hydroxylase activity, andmRNA levels. Hepatic sterol 27-hydroxylase activity and mRNAlevels are induced by dietary cholesterol and fat in low respondingbaboons more than in high responding baboons. Thus, the abilityto induce sterol 27-hydroxylase determines the LDL cholesterolresponse in baboons. High HDL response baboons often have highlevels of HDL₁ in their plasma. Our studies suggest that theN-terminal fragment of apo C-I with 38 amino acids and a molecularweight of 4 kDa acts as a cholesteryl ester transfer inhibitorpeptide in high HDL₁ baboons. The inhibitor peptide associateswith apo A-1 in HDL to produce a modified apo A-1 protein witha molecular weight of 31 kDa. The inhibitor peptide is a geneproduct and the presence of this peptide produces an antiatherogenichigh HDL₁ phenotype.