Pulmonary allergic reactions impair systemic vascular relaxation in ragweed sensitive mice

Asthma is often associated with cardiovascular complications, and recent observations in animal models indicate that induction of pulmonary allergic inflammation increases susceptibility of the myocardium to ischemia and reperfusion injury. In this study, we used a murine model of allergen sensitization in which aspiration of allergen induces pulmonary and systemic inflammation, to test the hypothesis that pulmonary exposure to allergen alters vascular relaxation responses. BALB/C mice were sensitized by intraperitoneal injection of ragweed and challenged by intratracheal instillation of allergen. Airway hyperreactivity and pulmonary inflammation were confirmed, and endothelium-dependent and -independent reactivity of thoracic aorta rings were evaluated. Ragweed sensitization and challenge induced airway hyperreactivity to methacholine and pulmonary inflammation, but did not affect constrictor responses of the aortic rings to phenylephrine and K+ depolarization. In contrast, maximal relaxation of aortic rings to acetylcholine and sodium nitroprusside decreased from 87.6±3.9% and 97.7±1.2% to 32±4% and 51±6%, respectively (p<0.05). The sensitivity to acetylcholine was likewise reduced (EC??=0.26±0.05 μM vs. 1.09±0.16 μM, p<0.001). The results demonstrate that induction of allergic pulmonary inflammation in mice depresses endothelium-dependent and -independent vascular relaxation, which can contribute to cardiovascular complications associated with allergic inflammation.     

The effect of HTK solution modification by addition of prolactin on biochemical indices reflecting ischaemic damage to porcine kidney

IntroductionThe aim of our study was to evaluate the impact of perfusion with HTK solution, modified by the addition of prolactin (PRI), on selected biochemical parameters of porcine renal damage within 24 and 48 hours after the onset of cold ischemia time.MethodsEach study group consisted of 10 adult pigs. During harvesting the kidneys were rinsed with Ringer's solution (group 1), HTK (group 2), and HTK+PRL in a dose of 0.2 mg/dL, 0.02 mg/dL, and 0.01 mg/dL in groups 3, 4 and 5, respectively. The levels of lactate dehydrogenase, asparagine (AST) and alanine aminotransferases, lactates, total protein, potassium and calcium were determined in the perfusate. After 24 and 48 hours the rinsing procedure and the abovementioned tests were repeated.ResultsAfter 24 hours of storage, in 4 groups, significantly lower levels of LDH (U/L) were recorded compared with HTK solution alone, namely 235 ± 93 versus 271 ± 125 (perfusion minute, 0), and 55 ± 21 versus 125 ± 94 (30th minute). Similar behavior pattern was presented by AST (U/L) and potassium (mmol/L), and the results were 31 ± 8 versus 35 ± 12 and 16 ± 10 versus 29 ± 14, and 12 ± 3 versus 16 ± 3 and 10 ± 1 versus 13 ± 1, respectively. The changes described above were not observed in the 48th hour of reperfusion.ConclusionOur study results indicate the possibility of cytoprotective action of PRL after adding it to the fluid perfusing kidneys during cold ischemia. This effect, observed after 24 hours of storage, was to a considerable extent dose dependent. In our experiment the effect was pronounced only at 0.02 mg/dL supply of PRL.     

Dietary habits and stomach cancer in Mizoram, India

Background An extremely high prevalence of stomach cancer was observed in Mizoram (India), where the population consumes uncommon food. The relation of food habits and stomach cancer was examined in this study. Methods A hospital-based case-control study was conducted during 2001–2004 to determine the risk factors among 329 patients with histologically confirmed stomach cancer and 658 matched controls. Food habits were determined by personal interview. Results An elevated risk of stomach cancer was observed with frequent consumption of sa-um [odds ratio (OR) 3.4] (sa-um is fermented pork fat, a traditional food) and with frequent consumption of smoked dried salted meat (OR 2.8) and fish (OR 2.5). Soda (alkali), used as a food additive, increased the risk of stomach cancer (OR 2.9). Helicobacter pylori infection was not found to be an independent risk factor for carcinogenesis of stomach cancer in this study. However, when H. pylori infection interacted with consumption of sa-um or smoked dried meat, it showed a significant association. Conclusion Peculiar food habits in Mizoram might be associated with the high prevalence of stomach cancer in Mizoram along with other factors. H. pylori infection might increase the risk of stomach cancer, or it may play a role as a promoter of stomach cancer in Mizoram.     

Fourth branchial pouch sinus: A case report

The fourth branchial pouch sinus is a very rare developmental anomaly; it usually presents as a recurring abscess in the left side of the neck. A high index of suspicion, combined with Barium swallow and computed tomography scan, aids in diagnosis. A case of branchial pouch anomaly is reported here for its rarity and late presentation. Complete excision of the entire epithelial tract combined with ipsilateral thyroid lobectomy remains the mainstay of management.     

Endoscopic septoturbinoplasty: Our update series

Decades have passed since septoplasty was first introduced for the management of the nasal airway. Various modifications of the technique have been made to deal with the pathology of the nasal septum. The authors have used the nasal endoscope successfully for the ultraconservative management of the deviated nasal septum and turbinoplasty [inferolateral partial resection of the turbinate/s]. The present study is an update series of the previously published preliminary series, and comprises of 480 cases of deviated nasal septum who underwent endoscope aided septo-turbinoplasty [EAS] to improve the nasal airway. The subjective assessment of the efficacy of this procedure was done by visual analogue scoring system and the objective assessment was done by endoscopy. This study demonstrates significant improvement in relieving nasal obstruction and the contact areas. The authors advocate a combined approach-an endoscopic approach for inaccessible posterior deviation and a conservative traditional technique for accessible anterior segment [caudal septum].     

KTP-532 laser cordotomy for bilateral abductor paralysis

Various lateralization procedures have been described in the past to treat bilateral vocal cord paralysis. Though endoscopie lateralization gives good results in terms ofdecannulation rates, the postoperative voice quality is often poor. KTP-532 laser assisted posterior cordotomy was done in 3 cases. This preliminary study showd 100% decannulation rate and good post-operative voice quality. The latter was assessed both subjectively and objectively on VAGMI scales.     

FDA drug approval summaries: pemetrexed (Alimta)

The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta; Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol; Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting.On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit.     

Tobacco use and stomach cancer in Mizoram, India.

The incidence of stomach cancer in India is lower than that of any other country around the world. However, in Mizoram, one of the north-eastern state of India, a very high age-adjusted incidence of stomach cancer is recorded. A hospital-based case-control study was carried out to identify the influence of tobacco use on the risk of developing stomach cancer in Mizoram. Among the cases, the risk of stomach cancer was significantly elevated among current smokers [odds ratio (OR), 2.3; 95% confidence interval (95% CI), 1.4-8.4] but not among ex-smokers. Higher risks were seen for meiziol (a local cigarette) smokers (OR, 2.2; 95% CI, 1.3-9.3). The increased risk was apparent among subjects who had smoked for >or=30 years. The increased risk was significant with 2-fold increase in risk among the subjects who smoked for >or=11 pack-years. The risk increased with increasing cumulative dose of tobacco smoked (mg). Tuibur (tobacco smoke-infused water), used mainly in Mizoram, was seemed to increased the risk of stomach cancer among current users in both univariate and multivariate models (OR, 2.1; 95% CI, 1.3-3.1). Tobacco chewer alone (OR, 2.6; 95% CI, 1.1-4.2) showed significant risk. Tobacco use in any form [smoking and smokeless (tuibur and chewing)] increased the risk of stomach cancer in Mizoram independently after adjusting for confounding variables.     

Induction of permeability transition and swelling of rat brain mitochondria by glutamine

Exposure of rat cerebral mitochondria to 2-10 mM glutamine (Gln) for 20 min, produced a concentration-dependent, gradual decrease of light scattering reflecting mitochondrial swelling. The light scattering decreasing effect of 5 mM Gln was attenuated by 0.5 microM cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition (mPT) induction. Histidine (His), which is a potent inhibitor of high affinity Gln uptake to mitochondria, attenuated Gln-induced decrease of mitochondrial light scattering when added at equimolar concentration, and abolished the decrease when added at 15 mM concentration shortly before addition of Gln. His inhibited the uptake of 5 mM [14C]Gln in a concentration-dependent manner as measured during 3 min incubation. CsA did neither affect [14C]Gln uptake nor modified its inhibition by His. The effects of 5 mM His and 0.5 microM CsA on mitochondrial light scattering were additive, indicating that mitochondrial swelling represents a cumulative effect of Gln -driven entry of osmotically obligated water and induction of mPT. Addition of ammonium ions at neurotoxic concentrations neither influenced the decrease of light scattering induced by Gln, nor produced any change in light scattering when added alone. The results point to mitochondrial swelling and subsequent activation of mPT, as one of the potential mechanisms by which Gln induces metabolic disturbances in the brain in hyperammonemic conditions.