inhibitor11

Thursday, August 2, 2012

Insulin inhalation: NN 1998.

Insulin inhalation: NN 1998.

Drugs R D. 2004;5(1):46-9

Authors:

Abstract
Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal insulin administered once or twice daily. In 2003, the US FDA adopted new GMP guidelines requiring sterile production of inhalation products and their devices. Novo Nordisk, therefore, will need to repeat phase III studies following device optimisation. These studies may begin at the end of 2004 and will include efficacy studies for 6-12 months and safety studies for up to 2 years (Lehman Brothers, Equity research, 7 August 2003). A phase IIb, 12-week clinical trial in 107 patients with type 2 diabetes was completed in the US. This trial was designed to compare the safety and efficacy of pulmonary insulin delivered via AERx iDMS, with intensified treatment with subcutaneous insulin administered at mealtimes. The results of the study positively compared pulmonary insulin with intensified subcutaneous insulin. Aradigm Corporation has a total of 85 patents pertaining to its proprietary AERx drug delivery system. Among those granted patents, 18 patents cover pulmonary insulin formulation including the method of patient breathing technique during pulmonary delivery of insulin. This patent guides patients on how to breathe in certain defined ways to achieve an effective amount and reproducibility of blood levels of insulin.

PMID: 14725493 [PubMed - indexed for MEDLINE]

peptide synthesis companies Natural products custom peptide price

Insulin inhalation: NN 1998.

Insulin inhalation: NN 1998.

Drugs R D. 2004;5(1):46-9

Authors:

PMID: 14725493 [PubMed - indexed for MEDLINE]

potassium channel genes

Wednesday, August 1, 2012

Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin.

Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin.

J Dermatol Sci. 2010 Aug;59(2):123-8

Authors: Muizzuddin N, Hellemans L, Van Overloop L, Corstjens H, Declercq L, Maes D

Abstract
BACKGROUND: Differences in structural and functional skin characteristics have been linked with ethnical background. But racial differences in skin have not been thoroughly investigated by objective methods and the data are often contradictory.
OBJECTIVES: This study was undertaken to compare skin barrier-related parameters of the stratum corneum on African American, Caucasian and East Asian skin by objective measurements.
METHODS: Baseline values of trans epidermal water loss were collected on the face. Consecutive stratum corneum D-squame tape strippings were collected on the panelist's ventral forearm and face to evaluate skin barrier strength and cohesion. Stratum corneum ceramides, maturation, measured as the transglutaminase-mediated cross-linking of stratum corneum proteins, and stratum corneum trypsin like enzyme activity were measured on the D-squame tape strippings.
RESULTS: East Asian and to some extent Caucasian skin was characterized by low maturation and relatively weak skin barrier. African American skin was characterized by low ceramide levels and high protein cohesion in the uppermost layers of the stratum corneum. These data can be interpreted in terms of the high prevalence of xerosis in black skin and increased skin sensitivity in East Asian skin.
CONCLUSION: These results demonstrate that skin properties at the level of the stratum corneum vary considerably among these ethnic groups. This contributes to an improved understanding of physiological differences between these study populations.

PMID: 20654785 [PubMed - indexed for MEDLINE]

potassium channel genes potassium channel Paclitaxel

Promising outcomes of definitive chemoradiation and cetuximab for patients with esophageal squamous cell carcinoma.

Promising outcomes of definitive chemoradiation and cetuximab for patients with esophageal squamous cell carcinoma.

Cancer Sci. 2012 Jul 27;

Authors: Chen Y, Wu X, Bu S, He C, Wang W, Liu J, Guo W, Tan B, Wang Y, Wang J

Abstract
This study investigated cetuximab added to definitive concurrent chemoradiation for esophageal squamous cell carcinoma (ESCC). Previously untreated patients with stage II-IVa ESCC received cetuximab (400�mg/m(2) /wk in week 1, then�250 mg/m(2) /wk during weeks 2 to 8), paclitaxel (45 mg/m(2) /wk) and cisplatin (20 mg/m(2) /wk) in weeks 2 to 8 with 59.4Gy radiotherapy. EGFR status in tumor specimens was assessed. Thirty-one patients were enrolled and evaluated for toxicity. Of the 29 patients assessable for response, 20 (69.0%) had clinical complete response (CR). Over a median follow-up of 23.6 months, disease progression was observed in 7 patients. The 1- and 2-year progression-free survival (PFS) rates were 85.5% and 75.1%, respectively. PFS was shorter for patients with lymphatic metastatic disease than for those with locally confined tumor, one-year PFS rate was 78.7% and 92.3%, respectively (P = 0.038). Sixteen patients (55.2%) were immunohistochemically positive for EGFR. The patients with EGFR-expressing tumor had a CR rate of 75.0% compared to 61.5% in those�with negative EGFR expression (P = 0.024). The PFS for patients with EGFR-expressing tumor was longer compared with the PFS of patients with negative EGFR (P = 0.133). The patients with prominent cetuximab-induced rash (? grade 2) had better CR rate and PFS than those with no or grade 1 rash (P < 0.05). The rates of Grades 3/4 esophagitis, hematologic and dermatologic toxicities were 9.7%, 29.0% and 16.1%, respectively. The regimen of definitive chemoradiation plus cetuximab achieved good clinical response and has an acceptable safety profile in Chinese ESCC patients.

PMID: 22845557 [PubMed - as supplied by publisher]

compound library screening small molecule library custom peptide synthesis

The treatment of West syndrome: a Cochrane review of the literature to December 2000.

The treatment of West syndrome: a Cochrane review of the literature to December 2000.

Brain Dev. 2001 Nov;23(7):624-34

Authors: Hancock E, Osborne JP, Milner P

Abstract
BACKGROUND: West syndrome is an age dependent syndrome, which includes a peculiar type of epileptic seizure (infantile spasms), usually hypsarrhythmia and in the majority psychomotor retardation. Despite huge advances in medicine it still remains a poorly understood entity and although with newer imaging techniques we are more often able to elicit the underlying 'causes' of these spasms, still little is known about their pathophysiological basis and treatment remains problematic.
OBJECTIVES: To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of long-term psychomotor development, subsequent epilepsy, control of the spasms and side effects.
METHODS: A search of the central trials register of the Cochrane Epilepsy Group, medline database, embase database and the reference lists of all retrieved articles was undertaken. Correspondence with colleagues and drug companies and appeals at international conferences were also undertaken to try and discover unpublished data. All randomised controlled trials (RCTs) on the medical treatment of infantile spasms were included. Data was then extracted independently by the three reviewers and analysed using the RevMan software package.
MAIN RESULTS: We found ten small RCTs on the pharmacological treatment of infantile spasms. No unpublished trials were discovered. These ten studies looked at just 335 patients treated with a total of eight different pharmaceutical agents. Overall methodology of the studies was poor, partly because of ethical dilemmas such as giving placebo injections to children. No study considered the effects of treatment on long-term psychomotor development or onset of other seizure types. One small study found vigabatrin to be more efficacious in stopping infantile spasms in a group of patients with tuberous sclerosis than hydrocortisone. One underpowered study showed a trend for vigabatrin to be more efficacious than placebo in stopping infantile spasms, another two equally underpowered studies suggested adrenocorticotrophic hormone (ACTH) to be more efficacious than low-dose prednisone. It was not possible to compare reduction in the number of spasms between the different treatments because of differences in methods of analysis. Overall, only nine patients were reported to have been withdrawn from the trial treatments due to side effects and two deaths were reported.
CONCLUSIONS: There is still little evidence available on the optimum treatment for infantile spasms. Further trials with larger number of patients, and longer follow-up are required.

PMID: 11701267 [PubMed - indexed for MEDLINE]

high throughput screening solid phase Peptide synthesis compare peptide companies

Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin.

Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin.

J Dermatol Sci. 2010 Aug;59(2):123-8

Authors: Muizzuddin N, Hellemans L, Van Overloop L, Corstjens H, Declercq L, Maes D

PMID: 20654785 [PubMed - indexed for MEDLINE]

ATPase potassium channel genes potassium channel

Prognostic Models to Predict Survival in Non-Small-Cell Lung Cancer Patients Treated with First-Line Paclitaxel and Carboplatin with or without Bevacizumab.

Prognostic Models to Predict Survival in Non-Small-Cell Lung Cancer Patients Treated with First-Line Paclitaxel and Carboplatin with or without Bevacizumab.

J Thorac Oncol. 2012 Jul 26;

Authors: Hoang T, Dahlberg SE, Sandler AB, Brahmer JR, Schiller JH, Johnson DH

Abstract
BACKGROUND:: To determine prognostic factors and build a model to predict 1-year overall survival (OS) and 6-month progression-free survival (PFS) in advanced non-small-cell lung cancer (NSCLC) patients treated with first-line paclitaxel and carboplatin with or without bevacizumab. MATERIALS AND METHODS:: We analyzed 26 pretreatment clinical variables in 850 NSCLC patients treated in the randomized Eastern Cooperative Oncology Group 4599 study. Univariate and multivariate analyses were performed to identify prognostic factors. Cox regression with 50% randomly sampled data was used to build nomograms with a prognostic score assigned to each factor. The model was validated with the remaining 50% of data. RESULTS:: Eleven poor factors for OS (hazard ratio) were as follows: skin metastasis (4.49), body mass index less than 18.5 (2.09), increased serum lactate dehydrogenase (1.74), adrenal metastasis (1.52), performance status greater than 0 (1.45), low serum albumin (1.45), men (1.39), bone metastasis (1.39), large cell/not otherwise specified histology (1.29), mediastinal nodal metastasis (1.23), and treatment without bevacizumab (1.18). Seven poor factors for PFS were as follows: skin metastasis (3.13), treatment without bevacizumab (1.52), bone metastasis (1.41), liver metastasis (1.40), low serum albumin (1.39), performance status greater than 0 (1.21), and mediastinal nodal metastasis (1.14). Based on these factors, we built and validated two nomograms predicting 1-year OS and 6-month PFS. CONCLUSION:: Using our proposed models, the probability of survival with first-line paclitaxel and carboplatin with or without bevacizumab in nonsquamous NSCLC patients can be estimated. These prognostic models provide a tool for research design and clinical decision making, such as patient stratification and therapy selection.

PMID: 22843087 [PubMed - as supplied by publisher]

custom peptide synthesis antigenic peptides antigen peptide