Analysis of chemical compositions and larvicidal activity of nut extracts from Areca catechu Linn against Aedes (Diptera: Culicidae).

BACKGROUND: There is a growing need to use green alternative larvicidal control for Aedes larvae compared to chemical insecticides. Substantial reliance on chemical insecticides caused insecticide resistance in mosquito populations. Thus, research for alternate chemical compounds from natural products is necessary to control Aedes larvae. This study explores the analysis of chemical compositions from Areca catechu nut as a potential larvicide for Aedes (Diptera: Culicidae). METHODS: The Areca catechu nut collected from Ipoh, Perak, Malaysia was grounded into powder and used for Soxhlet extraction. The chemical analysis of the extracts and their structures were identified using the GCMS-QP2010 Ultra (Shimadzu) system. National Institute of Standards and Technology (NIST) Chemistry WebBook, Standard Reference Database 69 (https://webbook.nist.gov/chemistry/) and PubChem (https://pubchem.ncbi.nlm.nih.gov/), the two databases used to retrieve the synonyms, molecular formula, molecular weight, and 2-dimensional (2D) structure of chemical compounds. Next, following WHO procedures for larval bioassays, the extracts were used to asses larvicidal activity against early 4th instar larvae of Aedes aegypti and Aedes albopictus. RESULTS: The larvicidal activities were observed against early 4th stage larvae with different concentrations in the range from 200 mg/L to 1600 mg/L. The LC50 and LC95 of Aedes aegypti were 621 mg/L and 2264 mg/L respectively; whereas the LC50 and LC95 of Aedes albopictus were 636 mg/L and 2268 mg/L respectively. Mortality was not observed in the non-target organism test. The analysis using gas chromatography and mass spectrometer recovered several chemical compounds such as Arecaidine, Dodecanoic acid, Methyl tetradecanoate, Tetradecanoic acid , and n-Hexadecanoic acid bioactive components. These chemical constituents were used as additive formulations in pesticides, pest control, insect repellent, and insecticidal agents. CONCLUSIONS: Our study showed significant outcomes from the extract of Areca catechu nut and it deserves further investigation in relation to chemical components and larvicidal actions between different species of Aedes mosquitoes. Even though all these findings are fundamental, it may have some interesting potentials to be developed as natural bio-larvicidal products.

Tracheomalacia after thyroidectomy for retrosternal goitres requiring sternotomy- a myth or reality?

INTRODUCTION: Tracheomalacia after thyroidectomy is not well understood. Reports on tracheomalacia are conflicting, with some suggesting a high rate and other large cohorts in which no tracheomalacia is reported. The aim of our study was to assess the incidence and factors associated with tracheomalacia after thyroidectomy in patients with retrosternal goitres requiring sternotomy at a high-volume tertiary care referral centre. METHODS: A longitudinal cohort study was conducted from January 2011 to December 2019. All adult patients who underwent thyroidectomy with sternotomy were included. Tracheomalacia was considered when tracheal rings were soft compared with other parts (proximal or distal) of the trachea and required either tracheostomy or resection with anastomosis. The decision to perform a tracheostomy or to administer continuous or bilevel positive airway pressure postoperatively was made depending on the degree of tracheomalacia. Logistic regression analysis was used to assess factors associated with tracheomalacia. RESULTS: We evaluated 40 patients who underwent thyroidectomy with sternotomy. The mean age of our cohort was 48.7 ± 11.3 years and the population was predominantly female (67.5%). One patient required tracheal resection with anastomosis, and two patients required tracheostomy. Multivariable logistic regression analysis did not reveal any patient- or thyroid-related factor significantly associated with the development of tracheomalacia in our cohort. CONCLUSIONS: The incidence of tracheomalacia after thyroidectomy with sternotomy appears to be very low. However, the occurrence of tracheomalacia after thyroidectomy in cases of large goitre is possible and hence worrisome.

Combined use of a videolaryngoscope and a flexible bronchoscope for awake tracheal intubation when front-of-neck airway is not an option.

We report a case of successful tracheal intubation with the combined use of a videolaryngoscope and flexible bronchoscope in a patient with difficult airway when both techniques had individually failed. A 35-year-old man presented with airway obstruction due to massive neck swelling causing hypoxia, stridor and respiratory distress. He had a history of oral cancer which had been resected with bilateral neck dissection and free flap reconstruction 2 months previously. Due to extensive anterior neck swelling, we judged that front-of-neck airway would not be a suitable approach. After unsuccessful attempts at awake tracheal intubation with videolaryngoscopy and flexible bronchoscopy separately, we combined both techniques with a successful outcome. By using a combined technique to address the specific problems presented by this case, a life-threatening emergency was resolved. This case highlights why it is useful for anaesthetists to be familiar with multiple techniques to awake tracheal intubation, both individually and in combination.

Effect of neuromuscular training on functional throwing performance and speed in asymptomatic cricket players.

OBJECTIVE: To determine the effect of neuromuscular training on functional throwing performance and speed among asymptomatic cricket players. DESIGN: Single-subject A-B-A design. METHOD: Forty-three male asymptomatic sub-elite cricket players were recruited from Karnataka Institute of Cricket, Bangalore, India, with a mean age of 20.4 ±â€¯2.03 years. Throwing accuracy and throwing speed were measured using Functional Throwing Performance Index (FTPI) and radar gun respectively, at zero, 12, 24 and 30 weeks in accordance with the A-B-A single-subject design. The neuromuscular training of the throwing arm was performed for 12 weeks, two days a week of supervised training including rhythmic stabilization drills were performed. A non-supervised training session including shoulder strengthening programme was conducted three days a week. RESULT: Participants demonstrated significant improvement in throwing accuracy (p < 0.001) and speed (p < 0.001) after 12 weeks of neuromuscular training. Six weeks post-withdrawal of the neuromuscular training on throwing accuracy was not significant (p = 0.117), However, speed was sustained (p = 0.013). CONCLUSION: Neuromuscular training showed an improved efficiency in throwing performance following 12 weeks of training in sub-elite cricket players. The sustained effect was not observed following 6 weeks of withdrawal of training.

Role of variants rs5030717 and rs5030718 of TLR4 in the risk prediction of nephropathy, hypertension and dyslipidaemia in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus describes a metabolic disorder characterised by prolonged elevated blood glucose that brings a risk of developing microvascular and macrovascular disease. Several factors, such as dysregulation of the Toll-like receptor 4 (TLR-4), are reputed to contribute to the multiple pathophysiological disturbances responsible for impaired glucose homeostasis. We hypothesised that variants rs5030717 and rs5030718 of TLR4 are associated with diabetic nephropathy, hypertension and dyslipidaemia. MATERIAL & METHODS: We recruited 370 diabetics (122 with nephropathy, 119 with hypertension and 129 with dyslipidaemia) and 120 ethnicity matched healthy controls. TLR4 polymorphisms were evaluated using polymerase chain reaction followed by restriction fragment length polymorphism analysis. The genotyping data were compared between cases and controls using chi-square test and logistic regression analysis. RESULTS: Although there was no overall difference in the genotype frequencies of TLR4 rs5030717 in diabetes v controls, the genotype frequencies of diabetic dyslipidaemia cases compared with controls were different (p = 0.001). Overall, the rs5030718 GA and GG genotype frequencies in the entire diabetes cohort were different from those of the controls (p = 0.037), and the frequencies of diabetic nephropathy cases (p = 0.03) and diabetic dyslipidaemia cases were different (p = 0.001) compared with controls. There were no links with diabetic hypertension. CONCLUSION: TLR4 polymorphisms rs5030717 and rs5030718 may be useful in predicting those type 2 diabetics who are at risk of hypertension, nephropathy and/or dyslipidaemia.

Pharmacokinetics, pharmacodynamics, and cytotoxicity of recombinant orally-administrated long-lasting GLP-1 and its therapeutic effect on db/db mice.

Recombinant orally long-acting glucagon-like peptide 1 (rolGLP-1), a novel analog of native GLP-1 that can stimulate insulin secretion, was constructed via site-directed mutagenesis by our laboratory. This study was designed to investigate the pharmacokinetics, pharmacodynamics, and the cytotoxicity of rolGLP-1. Diabetic db/db mice were given 125I-rolGLP-1 through a single dose of oral administration to evaluate the pharmacokinetics of rolGLP-1 by trichloroacetic acid-Radioactive assay (TCA-RA). Separately, rolGLP-1 was orally administered to the db/db mice daily for 28 days to evaluate its therapeutic effect. In addition, the safety of rolGLP-1 was assessed based on cytotoxicity testing on the cell line SH-SY5Y by both the MTT assay and the cell counts method. The results showed that the half-life of rolGLP-1 in db/db mice was 68.2 h, which is longer than that of native GLP-1. Results after the 28 day treatment showed glucose homeostasis was improved. Furthermore, rolGLP-1 was also proved to mitigate insulin resistance, alleviate hyperinsulinemia and decreased glycosylated hemoglobin content. Lastly, no visible adverse events were observed in cytotoxicity treatments on SH-SY5Y. Our results revealed that oral administration of rolGLP-1 harbored a longer half-life and a good therapeutic effect for type 2 db/db mice. All the results suggest the capacity and safety of rolGLP-1 for further use as an anti-diabetic agent for type 2 diabetes.This study was supported by Project 863 of China (2008AA02Z205).

Multiple pulmonary micronodules in a patient with Crohn's disease.

Sarcoidosis is a terrific mimicker and can present in many different ways. The case of a middle-aged woman with Crohn's disease who attended the gastroenterology clinic for routine follow-up is presented. She had dry cough and breathlessness for a few weeks. A chest x-ray showed scattered multiple bilateral pulmonary micronodules. This finding on her chest x-ray posed a diagnostic challenge, especially in view of the fact that she was previously treated with immunosuppressants to control her Crohn's disease. A diagnosis of sarcoidosis was established by various tests including lung biopsy, which showed non-caseating granulomas. Within a few weeks of beginning systemic steroid treatment, improvement was noticed in symptoms and lung function tests.

Effect of captopril in the presence of kinin B2 receptor antagonist on duration of survival after prolonged coronary artery ligation in hypertensive rats.

In the present investigation, we evaluated the potential effects of captopril, an angiotensin-converting enzyme inhibitor, in the absence and presence of kinin B(2) receptor antagonist (D-Arg-[Hyp3-D-Phe7]-BK) on the duration of survival after prolonged coronary artery ligation in spontaneously hypertensive rats (SHR). The captopril treatment (16 and 32 microg/kg; i.v.) resulted in a significant (p < 0.05) increase in survival time of SHR when compared with that of saline-treated control SHR. Kinin B(2) receptor antagonist (4 microg/kg; i.v.) pretreatment abolished (p > 0.05) the beneficial effect of captopril on the survival time when compared with that in saline-treated control SHR. Both the ligation of coronary artery and captopril treatment resulted in a significant (p < 0.001) fall in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) of SHR when compared with those of the saline-treated control SHR. In addition, captopril administration caused a significant (p < 0.05) fall in SBP, DBP, and HR of SHR before ligation of the coronary artery (preligation). However, there was no significant change (p > 0.05) in SBP, DBP, and HR between saline- and kinin B(2) receptor antagonist plus captopril-treated SHR during preligation. These finding might indicate that captopril possesses a cardioprotective property as demonstrated by an increase in the survival time of SHR. This beneficial effect of captopril is mediated via the kinin B(2) receptor pathway because kinin B(2) receptor antagonist pretreatment blocked the captopril-induced increase in the survival time of SHR.

A New High-performance Liquid Chromatographic Method for Fludarabine and Fludarabine Phosphate Compounded in Liposomes.

A simple and reproducible high-pressure liquid chromatography (HPLC) method was developed to measure simultaneously the concentrations of both fludarabine and liposome-compounded fludarabine in plasma. In this method, hypoxanthine 9-B-D arabinofuranoside was used as an internal standard. Fludarabine, fludarabine phosphate, and hypoxanthine 9-B-D arabinofuranoside were extracted from plasma and were separated by means of isocratic elution from a C18 reversed-phase column. The mobile phase consisted of 5% (v/v) methanol in 10mM ammonium phosphate solution. The pH of the mobile phase was adjusted to 2.2 with 85% phosphoric acid. The detection wavelength was 260 nm, and the retention times for fludarabine, fludarabine phosphate, and hypoxanthine 9-B-D arabinofuranoside were 48, 27, and 12 minutes, respectively. The recovery efficiencies varied depending on the amount spiked; however, they were 89% and 58% for 10 micrograms/mL of fludarabine and fludarabine phosphate, respectively. The limits of quantification for fludarabine and fludarabine phosphate were 0.03 micrograms/mL and 0.5 micrograms/mL, respectively. The assay was reproducible, and the within-day coefficients of variation (n=4) were less than 6.9% and less than 8.7% for fludarabine and fludarabine phosphate, respectively. The between day variabilities (n=4) were less than 6.3% and less then 6.4% for fludarabine and fludarabine phophate, respecitvley. The assays were linear within the range of 0.025 to 10 micrograms/mL (r squared = 0.999) for fludarabine and 0.5 to 10 micrograms/mL (r squared = 0.999) for fludarabine phosphate.

The effect of bradykinin and its antagonist on survival time after coronary artery occlusion in hypertensive rats.

It is known that BK does play a role in the cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors. The present study therefore was conducted to examine the effects of bradykinin (BK) and its antagonist on survival time in spontaneously hypertensive rats (SHR) with coronary artery ligation for 15 min and continuously. We also evaluated the heart rate and blood pressure (BP) in the presence and absence of BK and BK2 receptor antagonist, D-Arg-[Hyp-D-Phe7]BK. Coronary artery was ligated in anaesthetized rats and they were artificially ventilated with room air (stroke volume, 4 ml; 48 strokes/min) as described by the previous investigators. Lead II elecrocardiogram (ECG) was recorded from subcutaneous steel needle electrodes. Results of this investigation indicated that BK treatment 4 microg/kg (i.v.) and 8 microg/kg (i.v.) caused significant (P < 0.05) increase in survival time in SHR with coronary artery ligation for 15 min and continuously as compare to their respective saline-treated controls. However, BK antagonist treatment 4 microg/kg (i.v.) abolished the increase in survival time caused by BK treatment. The mean values of survival time between the saline-treated and BK antagonist plus BK-treated rats did not differ significantly (P > 0.05). The heart rate and BP responses were greatly reduced (P < 0.001) in the presence of coronary artery ligation. These findings suggest that BK might have cardioprotective effect to increase the survival time in rats by activating BK2 receptors after coronary artery ligation.

Disposition of aerosolized liposomal amphotericin B.

Amphotericin B (AmB) is an important drug for the treatment of fungal infection, but toxicity limits the lung tissue doses which may be achieved through intravenous administration. Although incorporation of AmB in liposomes reduces these effects and increases the therapeutic index for intravenous administration, targeted delivery to lung tissues via inhaled liposomal AmB aerosol may be a more effective approach. Aerosolization of liposomal amphotericin B targets the lungs, the organs first infested by many fungi. Development of optimal aerosolized liposomal AmB therapies requires a better understanding of the effect that liposome surface charge has on lung clearance kinetics. In this work we evaluated the clearance kinetics and organ distribution of inhaled liposomal AmB in male Balb/C mice. Mice were exposed via nose only to AmB-containing liposomal aerosols having positive, negative, or neutral surface charge characteristics. The formulations were aerosolized using a Collison nebulizer. Groups of animals were euthanized at predetermined times and the lungs and other organs were analyzed for AmB. AmB was not detected in serum and other organs such as kidneys, liver, and brain. The disposition of neutral and positive liposomal amphotericin B in lungs followed biexponential kinetics. The alpha and beta phase half-lives for positive liposomes were 1.3 and 15.1 days, respectively, and 2.3 and 22 days for neutral liposomes. AmB delivered via negative liposomes exhibited monoexponential clearance with a half-life of 4.5 days. These results suggest that toxic side effects in nontarget tissues are minimal and may indicate a potential for long term protection against fungal infections.

Local urokinase delivery with the Channel balloon: device safety, pharmacokinetics of intracoronary drug delivery, and efficacy of thrombolysis.

The Channel balloon is a new local drug-delivery catheter that has the dual capability of high-pressure lesion dilation and low-pressure drug infusion. The purpose of this study was to assess the safety and efficacy of this device in the local delivery of urokinase in the porcine model. Three in vivo protocols were performed in 57 anesthetized swine to assess the safety of Channel balloon use in the coronary vasculature, the pharmacokinetics of local urokinase delivery, and the ability of the catheter to lyse intraluminal thrombus. First, safety studies were performed in 18 coronary vessels in 13 pigs to compare angiographic and histologic changes following use of the Channel balloon with conventional balloon angioplasty. Second, intramural deposition of 123I-labeled urokinase was measured in 24 coronary arteries in 20 pigs to assess the efficiency and technical determinants of urokinase delivery and the time course of intramural drug retention. Finally, an in vivo thrombus model was used in 24 pigs to compare the thrombolytic capacity of local urokinase delivery with the Channel balloon in comparison with conventional urokinase infusion techniques. All balloon inflations and drug infusions with the Channel balloon were well tolerated in all animals without adverse angiographic, hemodynamic, or electrical sequelae. Comparative histologic studies with the Channel balloon demonstrated no additional vessel trauma beyond that seen with conventional balloon angioplasty. Between 0.09 and 0.35% of infused urokinase was intramurally deposited, with intracoronary persistence for at least 5 h. Drug infusion pressure did not significantly affect drug deposition, although larger amounts of urokinase were deposited with larger balloon:artery ratios and higher urokinase concentrations. In comparison to conventional systemic and guiding catheter infusions, local delivery of urokinase with the Channel balloon resulted in higher levels of clot dissolution. These studies have demonstrated safe intracoronary use of the Channel balloon in the porcine model. Local infusion of urokinase with this device results in significant intramural drug deposition that persists for at least 5 h. In comparison with conventional thrombolytic techniques, local urokinase delivery with the Channel balloon may result in enhanced intravascular thrombolysis.

Factors associated with the release of cardiac troponin T following percutaneous transluminal coronary angioplasty.

BACKGROUND: Recent studies have suggested that immunoassay of cardiac troponin T (cTnT) provides a more sensitive measurement of myocardial necrosis than creatine kinase MB (CK-MB) mass concentration. HYPOTHESIS: The purpose of this study was to compare the release of cTnT and CK-MB isoenzyme in patients undergoing percutaneous coronary angioplasty, and to investigate the clinical, procedural, and angiographic correlates of abnormal elevations of both of these markers. METHODS: Total creatine kinase (total CK), CK-MB, and cTnT levels were measured immediately before and 12 h following intervention in 110 patients, including 100 consecutive patients undergoing coronary angioplasty and 10 control patients undergoing diagnostic cardiac catheterization. All patients had normal levels of all three markers at baseline. A postintervention total CK level > 225 U/l, an increase in CK-MB > 5.0 ng/ml, and/or an increase in cTnT > 0.04 ng/ml were considered indicative of myocardial injury. RESULTS: Coronary angioplasty was successfully performed in all 100 patients without emergency bypass surgery or death, although six patients required emergent placement of an intracoronary stent for threatened closure. Eight patients demonstrated an abnormal increase in total CK, including six who were undergoing primary angioplasty for an acute myocardial infarction. One of these patients sustained a Q-wave infarction. Post angioplasty, 18 patients had elevations of both CK-MB and cTnT, 23 had elevations of only cTnT, and the remaining 59 patients had elevations of neither. All patients with CK-MB elevation also had cTnT elevation. Neither serologic marker increased in the diagnostic catheterization control patients. In comparison with patients without postintervention cTnT rise, patients with abnormal cTnT levels had a higher incidence of complex lesion morphology (p < 0.01) and intracoronary thrombus (p < or = 0.0001) prior to coronary angioplasty, and a higher incidence of coronary dissection (p < or = 0.01), abrupt closure (p < or = 0.05), and side-branch occlusion (p < or = 0.01) during angioplasty. In patients with elevation of both cTnT and CK-MB, postintervention CK-MB levels were 12-fold higher and cTnT levels were 21-fold higher than in patients with isolated elevation of only cTnT (p < 0.01). CONCLUSIONS: These data indicate that > 40% of patients undergoing coronary angioplasty have evidence of minor degrees of myocardial damage, as evidenced by cTnT release. High-risk coronary lesions and both minor and major complications of angioplasty are associated with cTnT release. cTnT appears to be a more sensitive marker of myocardial injury than CK-MB under these circumstances. In comparison with isolated cTnT rise, elevation of both CK-MB and cTnT may be indicative of greater levels of myocardial injury.

New high-performance liquid chromatographic method for amphotericin B analysis using an internal standard.

A simple and reproducible HPLC method for the analysis of amphotericin B (AmB) in serum, lung and liver using natamycin as the internal standard was developed. AmB and natamycin were extracted from serum, lung and liver and were separated using an isocratic elution from C18 reversed-phase column. The mobile phase consisted of acetonitrile-10 mM acetate buffer pH 4.0 (37:63, v/v). The HPLC system had two detectors in series. One was set at 303 nm and the other at 383 nm for the detection of natamycin and AmB, respectively. The retention times of AmB and natamycin were 15 and 6 min, respectively. The recovery efficiency was 96%-70%. The limit of quantification was 0.1 microgram/ml. The assay was reproducible, the within-day coefficient of variation (n = 6) was < 8% for serum, lungs and liver. The between-day variability (n = 6) was < 7.7% for serum, liver and lungs at 1 microgram/ml or 1 microgram/g tissue concentration. The assay was linear within the range 1-40 micrograms/ml (r2 = 0.99).

Enzyme inhibitors: new and known polybrominated phenols and diphenyl ethers from four Indo-Pacific Dysidea sponges.

Extracts and pure compounds isolated from four samples of Dysidea sp. sponges collected from two geographically distinct regions of the Indo-Pacific (Chuuk Atoll and Fiji) were assayed against five different enzyme assays, four of which are relevant to anticancer drug discovery and one of which (15-lipoxygenase) may detect compounds significant in modulating the development of atherosclerotic plaque. The pure compounds that inhibited various enzymes were polybrominated phenols and polybrominated phenoxyphenols. Fourteen of these phenols were isolated, six of which were new compounds. A variety of the phenols inhibited inosine monophosphate dehydrogenase (IMPDH), guanosine monophosphate synthetase, and 15-lipoxygenase. No activity was observed with protein tyrosine kinase pp60v-src or matrix metalloprotease.

New cycloartanol sulfates from the alga Tydemania expeditionis: inhibitors of the protein tyrosine kinase pp60v-src.

Bioactivity-directed fractionation of the extracts of the green alga Tydemania expeditionis using the protein tyrosine kinase pp60v-src led to the isolation of three new cycloartanol disulfates, 1-3, which show modest inhibition of this enzyme. The structures were deduced by spectroscopic methods.

Synthetic antigens as immunogens: Part IV. Specificity of antisera developed to Gal beta 1-3(GlcNAc beta 1-6)GalNAc and GlcNAc beta 1-6GalNAc.

Antisera to the chemically synthesized trisaccharide, Gal beta 1-3(GlcNAc beta 1-6)GalNAc, and disaccharide, GlcNAc beta 1-6GalNAc, were developed using the diazophenyl bovine serum albumin derivatives. The binding specificity of the antisera were analyzed by enzyme immunoassays with structurally related, chemically synthesized oligosaccharides. The anti-trisaccharide antibody showed no reactivity to T antigenic structures which bear the Gal beta 1-3GalNAc moiety. The immunodominant area of the Gal beta 1-3(GlcNAc beta 1-6)GalNAc was contained in the GlcNAc beta 1-6GalNAc region of the molecule. The reactivity pattern of the anti-trisaccharide antibody, although directed to the disaccharide, did not exactly duplicate the reactivity pattern of the anti-disaccharide.

A diterpenoid lactone from Aplysia juliana.

A new diterpenoid lactone, angasiol acetate [1], has been isolated from the sea hare Aplysia juliana collected from the Karachi coastline of the Arabian ocean. The structure, including the absolute configuration of 1, was determined by single-crystal X-ray diffraction and spectroscopic techniques.