Comparative assessment of immunogenicity of recombinant insulin Aspart from BioGenomics and its originator NovoRapid® in adult patients with type 2 diabetes mellitus.

OBJECTIVES: To assess and compare the immunogenicity of recombinant Insulin Aspart [manufactured by BioGenomics Limited (BGL-ASP)] with its originator NovoRapid® (manufactured by Novo Nordisk) in adult patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: BGL-IA-CTP301 study was a randomized, open label, parallel group, multicenter phase-III clinical study to compare the efficacy and safety of recombinant Insulin Aspart 100 U/mL [manufactured by BioGenomics Limited (BGL-ASP)] with its reference medicinal product (RMP); NovoRapid® [manufactured by Novo Nordisk], in adult patients with Type 2 diabetes mellitus (T2DM). The primary objective of the study was to compare the immunogenicity of BGL-ASP and RMP; NovoRapid® in patient serum samples collected from phase-III clinical study. Immunogenicity was studied as the incidence of patients positive for anti-insulin Aspart (AIA) antibodies, developed against BGL-ASP/RMP at baseline, end of 12 week and end of 24 week of the treatment period. The changes in incidence of patients positive for AIA antibodies post-baseline were also studied to assess and compare the treatment-emergent antibody response (TEAR) between the treatment groups (BGL-ASP and RMP). Statistical evaluation was done by Fisher's exact test to compare the overall incidence of patients positive for AIA antibodies and the TEAR positives observed post-baseline in both the treated groups. An in-vitro neutralizing antibody assay (Nab assay) was also performed to study the effect of AIA antibodies in neutralizing the biological activity/metabolic function of the insulin. The neutralizing potential of AIA was studied by its effect on %glucose uptake. We also evaluated the association between AIA antibody levels and its impact on biological activity by studying the correlation between them. RESULTS: Analysis of immunogenicity data suggested that the percentage of patients positive for AIA antibodies until week 24 was similar and comparable in both the treatment groups, BGL-ASP and RMP; NovoRapid®. The changes in incidence of patients positive for AIA post-baseline in terms of TEAR positives were also similar and comparable between the treatment groups. The results of the Nab assay with confirmed positive AIA samples from BGL-ASP- and RMP-treated groups did not have any negative impact on %glucose uptake by the cells in Nab assay, confirming the absence of neutralizing antibodies in both the treatment groups. The correlation studies also showed absence of association between AIA antibody levels and percentage glucose uptake in both BGL-ASP and RMP-NovoRapid® treatment groups. CONCLUSIONS: The immunogenicity assessment based on the overall incidence of patients positive for AIA, changes in incidence of patients positive for AIA post-baseline, TEAR rates and absence of neutralizing antibodies, were found to be apparently similar and comparable in both the treatment groups (BGL-ASP and RMP). We conclude from our studies that the immunogenicity of BGL-ASP is similar and comparable to RMP and the observed immunogenicity in terms of anti-insulin Aspart antibody levels had no impact on the biological activity of insulin.

Punica granatum L. Hydrogel for Wound Care Treatment: From Case Study to Phytomedicine Standardization.

The pharmacological activities of many Punica granatum L. components suggest a wide range of clinical applications for the prevention and treatment of diseases where chronic inflammation is believed to play an essential etiologic role. The current work reports a case study analyzing the effect produced by a magistral formulation of ethanolic extracts of Punica granatum peels on a non-healing chronic ulcer. The complete closure of the chronic ulcer that was initially not responsive to standard medical care was observed. A 2% (w/w) P. granatum peels ethanolic extract hydrogel-based formulation (PGHF) was standardized and subjected to physicochemical studies to establish the quality control parameters using, among others, assessment criteria such as optimum appearance, pH range, viscosity and hydrogel disintegration. The stability and quantitative chromatographic data was assessed in storage for six months under two temperature regimes. An efficient HPLC-DAD method was established distinguishing the biomarkers punicalin and punicalagin simultaneously in a single 8 min run. PGHF presented suitable sensorial and physicochemical performance, showing that punicalagin was not significantly affected by storage (p > 0.05). Formulations containing extracts with not less than 0.49% (w/w) total punicalagin might find good use in wound healing therapy.

New isomers in the full seniority scheme of neutron-rich lead isotopes: the role of effective three-body forces.

The neutron-rich lead isotopes, up to (216)Pb, have been studied for the first time, exploiting the fragmentation of a primary uranium beam at the FRS-RISING setup at GSI. The observed isomeric states exhibit electromagnetic transition strengths which deviate from state-of-the-art shell-model calculations. It is shown that their complete description demands the introduction of effective three-body interactions and two-body transition operators in the conventional neutron valence space beyond (208)Pb.

Bullous allergic drug eruption with presence of myeloperoxidase and reorganization of the dermal vessels observed by using CD34 and collagen IV antibodies.

CONTEXT: Bullous allergic reactions are inflammatory skin disorders, presenting usually as a result of some type of reaction to medication. CASE REPORT: A 67-year-old female was evaluated for the presence of diffuse patches of erythema, microvesiculation, vesicles, crusts, and oozing of sudden appearance on the extremities and on the rest of the body after taking sulfamethoxazole in combination with trimethoprim. Skin biopsies for hematoxylin and eosin examination, as well as for direct immunofluorescence and immunohistochemistry analysis were performed. H&E staining demonstrated classic features. Direct immunofluorescence revealed strong deposits of fibrinogen in the vessels of the skin. The immunohistochemistry stain showed strong positivity of myeloperoxidase within the blister cavity. The distribution of the vessels around the inflammatory process were noticed by using antibodies to CD34 as well to collagen IV. CONCLUSIONS: sulfamethoxazole is catalysed by CYP2C9 and/or myeloperoxidase. Thus, myeloperoxidase appears to be of importance in this disorder.

Monocationic surfactant induced ultra structural changes in antibiotic resistant Escherichia coli.

BACKGROUND & OBJECTIVES: Cetrimide is a monocationic surfactant, commonly used for disinfection of hospital floors, equipments, for cleansing of burns and wounds, hand wash, etc. We evaluated whether antibiotic resistant (AR) Escherichia coli isolates from hospital settings (nosocomial pathogens) show any evidence of significant reduction in their susceptibility to cetrimide. Also the response of AR E. coli (nosocomial pathogens) to the action of cetrimide was assessed by studying the ultra structural changes induced using transmission electron microscopy (TEM). METHODS: A total of 165 clinical samples were screened for isolation of E. coli. Eighty two (49.6%) samples were positive for E. coli. Antibiotic susceptibility testing of E. coli isolates was carried out by Kirby Bauer method to isolate AR E. coli. The randomly selected AR E. coli isolate was treated with different concentrations of cetrimide and minimum inhibitory concentration (MIC) of cetrimide was determined by broth micro dilution method. This same isolate was used for performing time kill assay and TEM study. RESULTS: The test E. coli isolate showed resistance to 12 different antibiotics. The MIC of cetrimide against AR E. coli was 312.5 microg/ml. The ultra cellular structural changes in cetrimide treated AR E. coli revealed vacuole formation, disaxilization of nuclear material, loss of cytoplasmic granularity, bleb formation and cell lysis. CONCLUSION: Ultra structural changes induced by the action of cetrimide revealed cell damaging changes in the AR E. coli to be dose and time dependent. The results showed that antibiotic resistance does not alter any change in susceptibility of E. coli to cetrimide, which was found to be still an effective disinfectant against a nosocomial pathogen E. coli.

Discovery of highly excited long-lived isomers in neutron-rich hafnium and tantalum isotopes through direct mass measurements.

A study of cooled ¹97Au projectile-fragmentation products has been performed with a storage ring. This has enabled metastable nuclear excitations with energies up to 3 MeV, and half-lives extending to minutes or longer, to be identified in the neutron-rich nuclides ¹8³(,)¹84(,)¹86Hf and ¹86(,)¹87Ta. The results support the prediction of a strongly favored isomer region near neutron number 116.

Simultaneous determination of metformin in combination with rosiglitazone by reversed-phase liquid chromatography.

A simple, rapid, and precise reversed-phase liquid chromatographic method is developed for the simultaneous determination of metformin in combination with rosiglitazone. This method uses a Zorbax XDB C(18) 15-cm analytical column, a mobile phase of acetonitrile and buffer containing 10mM disodium hydrogen phsosphate, and 5mM sodium dodecyl sulphate in the ratio of 34:66 (v/v), and pH is adjusted to 7.1 with orthophosphoric acid. The instrumental settings are a flow rate of 1 mL/min, column temperature at 40 degrees C, and detector wavelength of 226 nm. The internal standard method is used for the quantitation of metformin and rosiglitazone. Methylparaben is used as an internal standard. The method is validated and shown to be linear. The correlation coefficients for metformin and rosiglitazone are 0.9996 and 0.9997, respectively. The relative standard deviation for six replicate measurements in two sets of each drug in the tablets is always less than 2%.

Simultaneous high-performance liquid chromatographic determination of pioglitazone and metformin in pharmaceutical-dosage form.

A simple, rapid, and precise method is developed for the quantitative simultaneous determination of metformin and pioglitazone in a combined pharmaceutical-dosage form. Separation is achieved with a Zorbax XDB C(18), 15-cm analytical column using buffer-acetonitrile (66:34, v/v) of pH 7.1, adjusted with orthophosphoric acid as the mobile phase. The buffer used in the mobile phase contains 10mM disodium hydrogen phosphate and 5mM sodium dodecyl sulphate in double-distilled water. The instrumental settings are flow rate of 1 mL/min, column temperature at 40 degrees C, and detector wavelength of 226 nm. The internal standard method is used for the quantitation of the ingredients of this combination. Methylparaben is used as an internal standard. The method is validated and shown to be linear for metformin and pioglitazone. The correlation coefficients for metformin and pioglitazone are 0.9991 and 0.9999, respectively. The relative standard deviations for six replicate measurements in two sets of each drug in the tablets are always less than 2%.

Liquid chromatographic method for the determination of rosiglitazone in human plasma.

A robust, accurate and sensitive high-performance liquid chromatographic method for the determination of rosiglitazone (I) in human plasma has been developed. Pioglitazone (II) was used as internal standard. Both I and II are extracted from plasma using a liquid-liquid extraction procedure. Isocratic separation of I and II is carried out using a reversed-phase Zorbax SB C(18), 15-cm column with mobile phase consisting of methanol and a mixed phosphate buffer (10 mM monobasic sodium phosphate and dibasic sodium phosphate, pH adjusted to 2.6 with ortho-phosphoric acid) in the ratio 30:70 (v/v) and quantified by UV detection at 245 nm. Linearity was established over the range 5-1250 ng/ml using 1 ml human plasma. The method is specific, the endogenous components in plasma do not interfere with I and II. C.V. (%) of intra-day samples is less than 5.0% at four concentrations tested namely 5, 10, 500 and 1000 ng/ml. Similarly, over the same nominal concentrations, the precision of inter-day (5 days) samples also results in C.V. (%) less than 5.0%. The recoveries of I and II from human plasma were about 79 and 60%, respectively. This method can be used for routine clinical monitoring of I.

Resuspension of soil as a source of airborne lead near industrial facilities and highways.

Geologic materials are an important source of airborne particulate matter less than 10 microm aerodynamic diameter (PM10), but the contribution of contaminated soil to concentrations of Pb and other trace elements in air has not been documented. To examine the potential significance of this mechanism, surface soil samples with a range of bulk soil Pb concentrations were obtained near five industrial facilities and along roadsides and were resuspended in a specially designed laboratory chamber. The concentration of Pb and other trace elements was measured in the bulk soil, in soil size fractions, and in PM10 generated during resuspension of soils and fractions. Average yields of PM10 from dry soils ranged from 0.169 to 0.869 mg of PM10/g of soil. Yields declined approximately linearly with increasing geometric mean particle size of the bulk soil. The resulting PM10 had average Pb concentrations as high as 2283 mg/kg for samples from a secondary Pb smelter. Pb was enriched in PM10 by 5.36-88.7 times as compared with uncontaminated California soils. Total production of PM10 bound Pb from the soil samples varied between 0.012 and 1.2 mg of Pb/kg of bulk soil. During a relatively large erosion event, a contaminated site might contribute approximately 300 ng/m3 of PM10-bound Pb to air. Contribution of soil from contaminated sites to airborne element balances thus deserves consideration when constructing receptor models for source apportionment or attempting to control airborne Pb emissions.

Should the association of physicians of India adopt family planning?

PIP: Basic sciences are growing exponentially. With that growth, the field of medical science is also expanding, marked by the creation of new specialties and subspecialties and the existence of newly in-depth understanding of already longstanding medical problems and phenomena. More comprehensive training in basic sciences is needed in both medical training and continuing medical education programs. The Association of Physicians of India (API) is a large and active academic association. Any new medical specialty should become involved in the association in order to benefit from the interaction among specialists from emerging specialties and between specialists and general physicians which comes with membership. API's annual conference is an important forum for the exchange of ideas. However, while the scientific program covers a wide range of issues, emerging specialties are often overlooked because delegates usually attend sessions on more traditional medical topics. API can help in the development of a specialty by declaring it the specialty of the year and organizing a special session on the subject at the annual conference, releasing a booklet on the specialty, highlighting the specialty in the association's journal, and conducting other promotion activities.^ieng