Background Increased lipid levels in blood contribute to increasing the risk of diabetic complications. Glucagon exerts lipid lowering effects in diabetic state. However, the mechanism behind the lipid reduction by glucagon independent of glucose homeostasis is not well understood. We assessed the actions of glucagon on lipid modulation in blood and markers in liver in hyperlipidemic hamsters and rats.Methods Male Sprague Dawley rats and Golden Syrian hamsters on a hyperlipidemic diet for 2 weeks were administered a single dose of glucagon by subcutaneous (SC, 150 and 300 mu g/kg) or intracerebroventricular (ICV, 15 and 30 mu g/animal) route. Effect of acute treatment was observed on tyloxapol-induced hypertriglyceridemia, corn oil-induced post-prandial lipemia, and bile flow. A repeated dose treatment by subcutaneous (300 mu g/kg) or intracerebroventricular (30 mu g/animal) route was done for 2 weeks, following which circulating and hepatic lipids, hepatic markers of lipid metabolism and bile flow were assessed.Results Acute administration of glucagon (SC and ICV) decreased triglyceride absorption, hepatic triglyceride secretion rate and increased excretion of cholesterol in bile fluid in dose related manner. Repeated dose treatment reduced circulating and hepatic lipids and mainly LDL, and enhanced cholesterol excretion in bile. In liver, expression of HMGCoA reductase was reduced while that of ABCA1 was increased after repeated treatment, whereas pair fed group did not show significant changes when compared to the control group.Conclusion These findings demonstrate that central as well as peripheral glucagon effectively reduces hyperlipidemia in rat and hamster model, by modulating hepatic lipid metabolism.

AbstractA series of tertiary amino compounds of type (I) is prepared as non‐steroidal GR antagonists.

A series of peptidomimetic containing bidentate pTyr mimetics (9a-w) are reported as potent and selective PTP1B inhibitors. Compounds (9p and 9q) showed excellent selectivity towards PTP1B over various PTPs, including TCPTP (in vitro), which confirms discovery of highly potent and selective PTP1B inhibitors.

Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver selectivity. These preliminary results confirm discovery of potent and liver selective passive GR antagonist for the treatment of T2DM.

One-pot synthesis of 3,4-diaryl substituted 2(5H)-furanones was established and its commercial application has been demonstrated by accomplishing total synthesis of rofecoxib, under mild reaction conditions, with good yields and purity.

A peptidomimetic based cyanopyrrolidine derivatives are reported as potent and selective DPP-IV inhibitors. Some of the test compounds (10l and 10m) showed excellent potency and selectivity towards DPP-IV over various serine proteases, without CYP inhibition.

A new series of gamma-lactam hydroxamate based TACE inhibitors was designed mainly by introducing various substitutions at the 2nd position of the quinoline nucleus to achieve high potency and good selectivity towards TACE over matrix metalloproteases (MMPs) and ADAM-10. In ex vivo TNF-alpha inhibitory activity assays, compounds 11o and 11p were identified as the most potent compounds. The in vitro TACE inhibitory activity, selectivity over MMPs and ADAM-10 and the in vivo TNF-alpha inhibitory activities of compounds 11o and 11p were assessed and lead compound 11p was identified. Preliminary toxicity and pharmacokinetic (PK) studies were conducted for compound 11p and it showed an improved PK and clean toxicological profile compared to standard compound 1. Altogether, these results demonstrated the discovery of highly potent and selective gamma-lactam hydroxamate based TACE inhibitors which show potential for the safe and effective treatment of inflammatory diseases.

[image omitted] A convenient and cost-effective synthesis of pharmacologically important tert-butyl-2-(4-2-aminoethyl)phenylthio)-2-methylpropanoate from commercially available 2-2-phenyl-1-ethanol is described.

Background: Comparative effectiveness research, medical product safety evaluation, and quality measurement will require the ability to use electronic health data held by multiple organizations. There is no consensus about whether to create regional or national combined (eg, “all payer”) databases for these purposes, or distributed data networks that leave most Protected Health Information and proprietary data in the possession of the original data holders. Objectives: Demonstrate functions of a distributed research network that supports research needs and also address data holders concerns about participation. Key design functions included strong local control of data uses and a centralized web-based querying interface. Research Design: We implemented a pilot distributed research network and evaluated the design considerations, utility for research, and the acceptability to data holders of methods for menu-driven querying. We developed and tested a central, web-based interface with supporting network software. Specific functions assessed include query formation and distribution, query execution and review, and aggregation of results. Results: This pilot successfully evaluated temporal trends in medication use and diagnoses at 5 separate sites, demonstrating some of the possibilities of using a distributed research network. The pilot demonstrated the potential utility of the design, which addressed the major concerns of both users and data holders. No serious obstacles were identified that would prevent development of a fully functional, scalable network. Conclusions: Distributed networks are capable of addressing nearly all anticipated uses of routinely collected electronic healthcare data. Distributed networks would obviate the need for centralized databases, thus avoiding numerous obstacles.

4-Aryl-substituted 2(5H)-furanones were prepared by reaction of diethylphosphono acetic acid and phenacyl bromides, followed by an intramolecular Horner-Emmons-type cyclization. Both the reactions were carried out in situ to give the desired 4-aryl substituted 2(5H)-furanone derivatives.

Previous studies concerning the microbiology of otitis media with effusion (OME) did not correlate the past use of antimicrobial agents with the recovered organism's antimicrobial susceptibility. A retrospective analysis of cultures obtained from aspirates of 129 children with OME was performed. The study identified the isolated organisms and determined their susceptibility to the most recently administered antimicrobials. Bacterial growth was noted in 58 (45 per cent) patients. Aerobic organisms only were recovered in 37 aspirates (63 per cent of the culture-positive aspirates); anaerobic bacteria in seven (12 per cent); and mixed aerobic and anaerobic bacteria in 14 (24 per cent). A total of 92 bacterial isolates were recovered, accounting for 1.6 isolates per specimen (1.1 aerobes and 0.5 anaerobes). There were a total of 66 aerobic isolates, including Haemophilus influenzae non type-b (20 isolates), Streptococcus pneumoniae (17), and Staphylococcus spp. (seven). Twenty-six anaerobes were recovered, including Peptostreptococcus spp. and Prevotella spp. (eight each) and Propionibacterium acnes (four). Resistance to the antimicrobial used was found in 60 (65 per cent) isolates, recovered from 41 (71 per cent) of the patients. Of the 41 patients in whom resistance was detected, 37 (90 per cent) had been treated within three months of culture and four (10 per cent) had completed treatment more than three months before the cultures were taken (p < 0.01). The highest rate of recovery of resistant organisms was following trimethoprim-sulfamethoxazole (96 per cent), amoxycillin (71 per cent), and azithromycin (56 per cent). Of the patients treated with amoxycillin, H influenzae predominated. S pneumoniae was recovered from four of the seven (57 per cent) after trimethoprim-sulfamethoxazole, four of 14 (29 per cent) following amoxycillin, and three of 11 (27 per cent) after azithromycin. The data illustrate the relationship between resistance to the antimicrobials given to children and their recovery from the middle ear of patients with OME.

OBJECTIVEWe sought to compare the effect on the adenoid bacterial flora of patients with recurrent otitis media of antimicrobial therapy with amoxicillin (Am) or clindamycin (C).PATIENTS AND METHODSForty‐five children scheduled for elective adenoidectomy participated in a prospective randomized study. They were divided into 3 groups of 15 each to receive either no therapy (control) or 10 days of therapy with Am or C. Core adenoid tissues was quantitatively cultured for aerobic and anaerobic bacteria.RESULTSPolymicrobial aerobic‐anaerobic flora were present in all instances. The predominant aerobes in all groups were α‐hemolytic and γ‐hemolytic streptococci, Haemophilus influenzae, Staphylococcus aureus, group A β‐hemolytic streptococci, and Moraxella catarrhalis. The prominent anaerobes were Peptostreptococcus, Prevotella, and Fusobacterium spp. The number of isolates was significantly reduced in those treated with Am (n = 110, P < 0.05) or C (n = 58, P < 0.001) compared with control (n = 148). The number of bacteria per gram/tissue was lower in those treated with either antibiotics. The number of potential pathogens was lower in those treated with C compared with the other 2 groups (P < 0.001). The number of β‐lactamase‐producing bacteria was lower in those treated with C than in those treated with Am (P < 0.025) or control (P < 0.001).CONCLUSIONSThese data illustrate the ability of C and, to a lesser degree, of Am to reduce the bacterial load as well as potential pathogens and β‐lactamase‐producing bacteria from the adenoids of children with recurrent otitis media.

OBJECTIVE:To determine the qualitative and quantitative microbiology of core adenoid tissue obtained from four groups of 15 children each, with recurrent otitis media (ROM), recurrent adenotonsillitis (RAT), obstructive adenoid hypertrophy (OAH), and occlusion or speech abnormalities (controls).METHODS:Core cultures of surgically removed diseased adenoids and of healthy controls were cultured for aerobic and anaerobic bacteria.RESULTS:Polymicrobial aerobic-anaerobic flora were present in all instances. Ninety-four organisms were isolated from control specimens, and 148 from ROM, 142 from RAT, and 149 from OAH specimens. The predominant aerobes in all groups were alpha-hemolytic and gamma-hemolytic streptococci, Haemophilus influenzae, Staphylococcus aureus, group A beta-hemolytic streptococci, and Moraxella catarrhalis. The prominent anaerobes were Peptostreptococcus, Prevotella, and Fusobacterium species. The number, concentration and distribution of types of most organisms did not vary among the three groups of diseased adenoids. However, the number of those that are potential pathogens and those that produced beta-lactamase was lower in the control than the diseased adenoids (P < .001).CONCLUSION:The study highlights the importance of the bacterial load in the adenoids in contributing to the etiology of ROM, RAT, and OAH.

The microbiologic features of infected sinus aspirates in nine children with neurologic impairment were studied. Anaerobic bacteria, always mixed with aerobic and facultative bacteria, were isolated in 6 (67%) aspirates and aerobic bacteria only in 3 (33%). There were 24 bacterial isolates, 12 aerobic or facultative and 12 anaerobic. The predominant aerobic isolates were Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus (2 each) and Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae (1 each). The predominant anaerobes were Prevotella sp. (5), Peptostreptococcus sp. (4), Fusobacterium nucleatum (2), and Bacteroides fragilis (1). Beta-lactamase-producing bacteria were isolated from 8 (89%) patients. Organisms similar to those recovered from the sinuses were also isolated from tracheostomy site and gastrostomy wound aspirates in five of seven instances. This study demonstrates the uniqueness of the microbiologic features of sinusitis in neurologically impaired children, in which, in addition to the organisms known to cause infection in children without neurologic impairment, facultative and anaerobic gram-negative organisms that can colonize other body sites are predominant.

The microbiology of in 55 ear aspirates obtained from 34 children with chronic otorrhea was studied. Aspiration of the middle ear exudate was done immediately following removal of tympanostomy tube (TT). The middle ear aspirates and swab specimens of the external auditory canals were cultured for aerobic and anaerobic bacteria. Sixty-five isolates were recovered only from the middle ears, 73 only from the external ear canals, and 73 were present at both sites. Analysis of the 138 middle ear isolates demonstrated the recovery of aerobic bacteria only in 28 patients (50%), anaerobes only in seven (13%), and both aerobes and anaerobes in 20 (36%). There were 77 aerobic and 61 anaerobic isolates. Commonly recovered aerobes were Pseudomonas aeruginosa (17 isolates), Staphylococcus aureus (11), Proteus sp. (7), Moraxella catarrhalis (6), Klebsiella pneumoniae (5) and non-typable Haemophilus influenzae (5). Commonly isolated anaerobes were Peptostreptococcus sp. (25 isolates), Prevotella sp. (10), Bacteroides sp. (8) and Fusobacterium sp. (6). Pseudomonas aeruginosa and S. aureus were more often isolated in children older then 6 years. These findings demonstrate the polymicrobial bacteriology of TT-related otorrhea in children. Specimens collected from the external auditory canals can be misleading. Reliable information can be obtained from the ear exudes when collected through the TT or through the open perforation after their removal.

The hematologic manifestations of 100 pediatric patients with AIDS/ARC were reviewed. Acute or chronic anemia was present in 94% of all patients. Two patients had autoimmune hemolytic anemia and 1 patient had an aplastic anemia. A positive Coombs test was detected in 40% of all patients. Leukopenia and neutropenia occurred in 50% and 40% of patients respectively. Antineutrophil antibodies were detected in 2 patients. Ten of 13 children developed neutropenia on Bactrim. Forty percent of all children were lymphopenic. Monocytosis and eosinophilia occurred in 66% and 40% of patients respectively. Thrombocytopenia was seen in 33% and of these 25% developed a persistent thrombocytopenia. Platelet antibodies were detected in 10 of 11 patients. Pancytopenia occurred in 20% of children with opportunistic infection (O.I.). Acquired Von Willebrands disease and autoantibodies to Factors X, XI and XII were seen in 2 individuals. Peripheral smears revealed ovalocytes, microcytosis, hypochromia and atypical lymphocytes. Bone marrow examination showed hypercellularity, myeloid hyperplasia and increased plasma cells and lymphocytes. Decreased erythropoeisis, dysmyelopoeisis, dyserythropoeisis and megaloblastic changes were occasionally seen. Bone marrow cultures were positive for mycobacterium avium intra cellulare (4), Candida (2) and CMV (1) in a total of 7 patients.

Pediatric PulmonologyVolume 3, Issue 4 p. 280-281 Case Report Clinical Candida supraglottitis in an infant with AIDS-related complex Dr. Michael R. Bye MD, Corresponding Author Dr. Michael R. Bye MD Divisions of Pulmonary Medicine, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New YorkPediatric Pulmonary Medicine, Albert Einstein College of Medicine, Jacobi Hospital Room 817, Pelham Parkway and Eastchester Road, Bronx, NY 10461Search for more papers by this authorAnthony Palomba MD, Anthony Palomba MD Critical Care, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New YorkSearch for more papers by this authorLarry Bernstein MD, Larry Bernstein MD Allergy/Immunology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New YorkSearch for more papers by this authorKiran Shah MD, Kiran Shah MD Allergy/Immunology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New YorkSearch for more papers by this author Dr. Michael R. Bye MD, Corresponding Author Dr. Michael R. Bye MD Divisions of Pulmonary Medicine, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New YorkPediatric Pulmonary Medicine, Albert Einstein College of Medicine, Jacobi Hospital Room 817, Pelham Parkway and Eastchester Road, Bronx, NY 10461Search for more papers by this authorAnthony Palomba MD, Anthony Palomba MD Critical Care, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New YorkSearch for more papers by this authorLarry Bernstein MD, Larry Bernstein MD Allergy/Immunology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New YorkSearch for more papers by this authorKiran Shah MD, Kiran Shah MD Allergy/Immunology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New YorkSearch for more papers by this author First published: July/August 1987 https://doi.org/10.1002/ppul.1950030415Citations: 18AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Claesson B, Trollfors B, Ekstrom-Jodal B, et al. Incidence and prognosis of acute epiglottitis in children in a Swedish region. Pediatr Infect Dis 1984; 3: 534–538. 2 MayoSmith MF, Hirsch PJ, Wodzinski SF, Schiffman FJ. Acute epiglottitis in adults. N Engl J Med 1986; 314: 1133–1139. 3 Costigan DC, Newth CJL. Respiratory status of children with epiglottitis with and without and artificial airway. Am J Dis Child 1983; 137: 139–141. 4 CDC. Update: Acquired immunodeficiency syndrome. Morbid Mortal Weekly Rep 32: 688–691. 5 Wood RE. Spelunking in the pediatric airways: Explorations with the flexible fiberoptic bronchoscope. Pediatr Clin North Am 1984; 31: 785. 6 Kobayashi RH, Rosenblatt HM, Carney JM. Candida esophagitis and laryngitis in chronic mucocutaneous candidiasis. Pediatrics 1980; 66: 380–384. 7 Jacobs RF, Yasuda K, Smith AL, Benjamin DR. Laryngeal candidiasis presenting as inspiratory stridor. Pediatrics 1982; 69: 234–236. 8 Hughes WT. Systemic candidiasis: A study of 109 fatal cases. Pediatr Infect Dis 1982; 1: 11–18. Citing Literature Volume3, Issue4July/August 1987Pages 280-281 ReferencesRelatedInformation

Between October, 1985 and May 1987, 29 children (mean age 22 ± 22 months, range 2–54 months) with AIDS or ARC developed acute respiratory illness. The initial diagnostic procedure was flexible fiberoptic bronchoscopy, with bronchoalveolar lavage (BAL). BAL was positive for Pneumocystis carinii in 14 and for respiratory syncytial virus, Staphylococcus aureus , and Escherichia coli in 3 additional patients. Subsequent lung tissue analysis and/or clinical course suggested no false negative lavages. Complications possibly related to the procedure occurred in two patients. We find BAL an effective diagnostic technique in these patients, offering a less invasive alternative to open lung biopsy.

Aspirates of serous ear fluids from 57 children were examined for aerobic and anaerobic bacteria. Bacterial growth was noted in 23 patients (40 per cent). Aerobic organisms only were recovered in 13 aspirates (57 per cent of the culture-positive aspirates); anaerobic bacteria in four (17 per cent); and mixed aerobic and anaerobic bacteria in six (26 per cent). A total of 45 bacterial isolates were recovered, accounting for 2.0 isolates per specimen (1.4 aerobes and 0.6 anaerobe). There were a total of 31 aerobic isolates, including Hemophilus influenzae (eight isolates), Staphylococcus aureus and Streptococcus pneumoniae (five of each), and Staphylococcus epidermidis and alpha-hemolytic streptococcus (four of each). Fourteen anaerobes were recovered, including anaerobic gram-positive cocci and Bacteroides melaninogenicus (five isolates each) and Propionibacterium acnes (three isolates).