•Harmonized pharmacopoeial peptide monograph will reduce manufacturer’s burden.•Quality assessment of peptides is crucial to ensure optimal safety to patients.•Purity characterization of peptides is ...critical for development of peptide therapeutics.•Global peptides therapeutic market is predicted to flourish in near future.
Exquisite selectivity, remarkable efficacy, and minimal toxicity are key attributes inherently assigned to peptides, resulting in increased research interest from the pharmaceutical industry in peptide-based therapeutics (PbTs). Pharmacopoeias develop authoritative standards for PbT by providing standard specifications and test methods. Nevertheless, a lack of harmonization in test procedures adopted for PbT in the latest editions of Pharmacopoeias has been observed. Adoption of a harmonized monograph could increase further the interest of the global pharmaceutical industry in PbTs. Here, we provide an overview of pharmacopoeial methodologies and specifications commonly observed in PbT monographs and highlight the main differences among the pharmacopoeias in terms of the active pharmaceutical ingredients that they focus on. We also address the prospects for PbTs to mature as a new therapeutic niche.
The article provides an interpharmacopoeial comparison of quality specifications of peptide-based drug monographs and areas for improvement in peptide therapeutics.
Background
Patch test is the gold standard for diagnosing allergic contact dermatitis. Conventionally, the patches are applied for 48 h, which in tropical weather conditions causes excessive ...sweating, leading to irritation, and sometimes the patches come off, making the test inconclusive.
Objective
To compare the patch test positivity after 24 and 48 h of occlusion time in patients of allergic contact dermatitis, using standard allergen concentration.
Materials and methods
Clinically suspected patients of allergic contact dermatitis were enrolled and patch tested using the Indian Standard Series, parthenium acetone extracts (1:50, 1:100 and 1:200 dilutions) and patient material. Patches were applied in duplicate on either side of the back, using a random number table. One set of patches was removed after 24‐h of occlusion, while the other set after 48‐h. Readings were performed at 48‐ and 96‐h by two independent dermatologists, blinded to the duration of occlusion.
Results
The study had 97 adult patients (58 males and 39 females; mean age: 48.12 ± 13.07 years). A total of 133 and 142 positive reactions were observed after 48 h occlusion at 48 and 96 h reading, respectively. Of these 117 (87.9%) and 132 (92.9%) patches were positive and concordant and noted at 24 h occlusion time. The Cohen's kappa coefficient were 0.94 for 48 h and 0.97 for 96 h reading, hence showing an almost complete agreement (ⱪ > 0.81) between patches occluded for 24 and 48 h.
Conclusion
Though there is no significant difference in patch test positivity among ISS allergens after either occlusion time, 48 h occlusion performs significantly better compared with 24 h, when reactions of all allergens (ISS, patient material and parthenium acetone extract) are analysed together.
Our study compares patch test positivity in 97 patients of allergic contact dermatitis after 24 and 48 h of application. Using standard allergen concentrations, we found no significant difference in Indian Standard Series allergens. However, when analysing all allergens together, 48 h application outperformed 24 h. Moreover, positive reactions after 48 h had increased severity (grading) as compared with after 24 h. Our results suggest that a shorter occlusion time may be sufficient, enhancing patient comfort and test reliability, particularly in tropical climates. Consideration for a new standard occlusion time is proposed, with further multicentre studies needed for validation.
The objective of this paper is to estimate the reliability function and mean time to system failure of a
k-
out-of
-n
system which consists of
n
independent and identically distributed components ...with life times following Weibull model. The system is operational until at least
k
of its
n
components are functional. The Reliability characteristics are obtained using uncensored failure observations by both the maximum likelihood estimation and Bayesian methods. The Bayes estimates are obtained using Lindley’s approximation technique with non-informative and informative priors under squared error loss function. The asymptotic confidence interval is constructed for the reliability function using maximum likelihood estimator. A simulation study is carried out for comparing the performances of these estimates with respect to their mean squared errors. Analysis of a real data set is also given.
In the recent years, number of threats to network security increases exponentially as the Internet users which poses serious threat in cloud storage application. Detection and defending against the ...multiple threats are currently a hot topic in industry and considered as one of the challenging research in academia. Many methodologies and algorithms devised to predict the different attacks. Still, most of the methods cannot simultaneously achieve high performance of prediction with a small number of false alarm rates. In this scenario, Deep Learning (DL) algorithms are appropriate and intelligent to categorize the multiple attacks. Still, most of the existing DL techniques are computationally inefficient that may degrade the performance in predicting the both normal and attack information. To overcome this aforementioned problem, this paper proposes the hybrid combination of attention maps with deep recurrent networks to mitigate the multiple attacks with low computational overhead. Initially, the pre-processing step is proposed to the inputs in a specified range. Later on, input data are fed into the Attention Enabled Gated Recurrent Networks (AEGRN) which is used to remove the redundant features and select the optimal features that aids for the better classification. Further to enhance the faster response, deep feed forward layers are proposed to replace the traditional deep neural networks. Numerous metrics for performance, including accuracy, precision, recall, specificity, and F1-score, are examined and analyzed as part of the thorough experimentation utilizing multiple datasets, including NSL-KDD-99, UNSW -2019, and CIDC-001. Comparisons of performance between the method that is suggested and existing models developed with DL are used to demonstrate the proposed algorithm's supremacy. The suggested framework surpasses the other DL models and has the best accuracy in predicting with little computational overhead, according to an investigation.
A collaborative study was conducted to establish the first Indian Pharmacopoeia Reference Standard (IPRS) for teriparatide to be used in quality control testing of marketed products in compliance ...with the Indian Pharmacopoeia (IP) monograph. The study objective was to evaluate the candidate standard in terms of the WHO International Standard (IS) to assign its content in mg per vial terms. This study involved four laboratories from India and the candidate standard was calibrated against the WHO IS by each participant laboratory using high-performance liquid chromatography (HPLC) assay method per IP monograph. Direct calibration of the candidate standard resulted in an assigned content of 1.02 mg per vial. Based on the study results the candidate standard was judged suitable to serve as the first IPRS for teriparatide for identification and assay by HPLC.
•Collaborative study to establish first Indian Pharmacopoeia Reference Standard (IPRS) for teriparatide.•Calibration of the candidate standard in terms of the WHO International Standard.•Study assigned the content of candidate standard as 1.02 mg per vial.•Candidate standard judged suitable to serve as first IPRS for teriparatide for identification and assay by HPLC.
Aim
To investigate the correlation between the concentration of active‐matrix metalloproteinases‐9 (aMMP‐9) in pulpal blood and the outcome of pulpotomy in mature permanent teeth with symptomatic ...irreversible pulpitis (SIP).
Methodology
Forty permanent molar teeth with a clinical diagnosis of SIP and normal apical tissues with periapical index (PAI) score ≤ 2 and ten permanent teeth (8 molars and two premolars) with a diagnosis of normal pulp that required root canal treatment for prosthetic reasons from patients between the ages of 15–35 years were recruited. All clinical procedures were performed under local anaesthesia and rubber dam isolation. After access opening, the coronal pulp tissue was amputated up to the canal orifice. A 100 μL volume of the pulpal blood was collected using a micropipette and transported to the laboratory. Sodium hypochlorite (2.5 %) was used as a haemostatic agent, and mineral trioxide aggregate (MTA) was used as the pulp capping material. The tooth was restored with composite at the same visit. Teeth with normal pulps were treated with single‐visit root canal treatment. Patients with pulpotomy were recalled at 6 and 12 months. Outcome assessment of teeth with pulpotomy was carried out at 12 months and was categorized as success (asymptomatic patients with PAI score ≤ 2) or failure (symptomatic patients or PAI score ≥ 3). Quantification of aMMP‐9 in pulpal blood was achieved using a fluorometric assay. The following statistical analyses were performed to assess the data: t‐test, Fisher's exact test, kappa coefficient, non‐parametric test, Wilcoxon rank‐sum test, Spearman rank correlation test and receiver operating characteristic curve (ROC).
Result
The success rate of pulpotomy was 88 % at 12‐months. There was a significant difference between the median concentrations of aMMP‐9 in pulpal blood of teeth with normal pulps (52 (12–96) ng mL−1:) and SIP (193.3 (25.8–607.7) ng mL−1:) (P = 0.0003) and successful (132.3 (25.8–548.3) ng mL−1:) and failed cases (512.4 (334.8–607.7 ng mL−1:) (P = 0.0015) of MTA pulpotomy. A significant association was established between aMMP‐9 concentration and outcome of pulpotomy. The area under the receiver operating characteristics curve (0.9484, 95%CI) suggested excellent discriminatory power of aMMP‐9 concentration in pulpal blood to predict the pulpotomy outcome.
Conclusion
The pulpal blood concentration of aMMP‐9 was significantly associated with the outcome of pulpotomy in teeth with symptomatic irreversible pulpitis, where it may be used as a potential prognostic biomarker.
Background & objectives: Research studies in the 1970s reported that in pre-school children, undernutrition increased the risk of infections and infections aggravated undernutrition. Over decades, ...there has been a reduction in prevalence of undernutrition and improvement in access to healthcare for treatment of infections. A mixed longitudinal study was undertaken to assess whether over time there were any changes from the earlier reported effect of undernutrition prior to infection on the risk of morbidity and effect of morbidity on nutritional status in pre-school children.
Methods: Pre-school (0-59 months of age) children from urban low- and middle-income families whose parents were willing to allow their participation in the study were enrolled. Information on sociodemographic profile of the families was collected at enrolment. Weight of all children and length in infants were recorded every month; length/height in children 12-59 months of age was recorded once in three months. Morbidity information was collected through fortnightly visits.
Results: 3888 pre-school children were followed up in 74636 home visits. Among these children, underweight and wasting were associated with a small increase in risk of infections. The odds ratio for risk of infection for underweight children was 1.09 (95% CI: 1.02 to 1.16) and for wasting was 1.18 (95% CI: 1.08 to 1.29). The deterioration in Z scores for weight-for-age and body mass index-for-age in children during illness and convalescence was small but significant (P<0.001).
Interpretation & conclusions: The increased risk of infections in undernourished children living in overcrowded tenements in areas with poor environmental hygiene was not significant, perhaps because the risk of infection in normally nourished children was also high. The deterioration in nutritional status following infection was small because of the ready access to and utilization of health and nutrition care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & objectives: In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the standardization ...of the management protocol for the same. In addition, there also exists diversity in the views about the clinical diagnosis, ancillary investigations and clinical parameters. The objective of the present study was to evaluate the reported outcomes of surgical interventions for the management of LSCD.
Methods: A systematic review of published literature on limbal stem cell transplantation (LSCT) was performed using Ovid Medline, Embase and PubMed for a duration of 2009 to 2019. Original studies including prospective, retrospective case series and randomized controlled trials, articles in English language, articles with access to full text and studies with more than or at least 10 patients were included in this review. Data related to clinical and visual outcomes were evaluated, and pool estimates of different surgeries were calculated using random-effects model and individually using Pearson's Chi-square test.
Results: A total of 1133 abstracts were evaluated. Finally, 17 studies were included for the analysis. Among these 17 studies, direct limbal lenticule transplantation was performed in five studies, of which autologous tissue from the fellow eye conjunctival limbal autograft (CLAU), allograft from a cadaver/live donor keratolimbal allograft (KLAL)/conjunctival limbal allograft (CLAL) and combination of CLAU plus KLAL were done in one, three and one studies, respectively. The ex vivo expanded cultivated limbal epithelial transplantation (CLET) was reported in six studies and simple limbal epithelial transplantation (SLET) in four studies. Two were comparative studies comparing CLET and CLAL (living-related CLAL) with cadaveric KLAL, respectively. Outcome analysis of the included studies showed significant heterogeneity. Calculated pool rate for various types of surgeries was calculated. The pool estimate for CLAL was 67.56 per cent 95% confidence interval (CI), 41.75-93.36; I2=83.5%, P=0.002. For KLAL, this value was 63.65 per cent (95% CI, 31.38-95.91; I2=92.4%, P=0.000). Pool estimate for CLET was 78.90 per cent (95% CI, 70.51-87.28; I2=73.6%, P=0.001). Corresponding values for SLET were 79.08 per cent (95% CI, 74.10-84.07; I2=0.0%, P=0.619). CLAU and combination of CLAU plus KLAL were done in one study each; hence, statistical analysis could not be done. The functional outcome in terms of gain in visual acuity post-operatively was better in KLAL (P<0.005) and SLET group as compared to CLET group.
Interpretation & conclusions: The present analysis suggests that though the anatomical success rates were almost identical between SLET, CLET, CLAL, and KLAL procedures, the functional success rates were better following KLAL and SLET procedures as compared to CLET. Decision for LSCT for cases of ocular burns based on either clinical judgement of the surgeon or individual diagnosis remains a suitable option.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Designer foods are normal foods fortified with health promoting ingredients. These foods are similar in appearance to normal foods and are consumed regularly as a part of diet. In this article we ...have reviewed the global regulatory status and benefits of available designer foods such as designer egg, designer milk, designer grains, probiotics, designer foods enriched with micro and macronutrients and designer proteins. Designer foods are produced by the process of fortification or nutrification. With the advances in the biotechnology, biofortification of foods using technologies such as recombinant DNA technology and fermentation procedures are gaining advantage in the industry. The ultimate acceptability and extensive use of designer foods depend on proper regulation in the market by the regulatory authorities of the country and by creating consumer awareness about their health benefits through various nationwide programs.
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Aegle marmelos (L.) Correa is an Indian medicinal plant known for its vast therapeutic activities. In Ayurveda, the plant is known to balance “vata,” “pitta,” and “kapha” dosh. Recent ...studies suggest anti-inflammatory, anti-microbial, and anti-diabetic potential butlack in defining the dosage over thetherapeutic activities. This study aims to determine the chemical profile ofAegle marmelosfruit extract; identification, enrichment, and characterization of the principal active component(s) having anti-inflammatory and anti-diabetic potential.Targeted enrichment of total coumarins, focusing on marmelosin, marmesin, aegeline, psoralen, scopoletin, and umbelliferone, was done fromAegle marmelosfruit pulp, and characterized using advanced high-throughput techniques. In vitro and in silico anti-diabetic and anti-inflammatory activities were assessed to confirm their efficacy and affinity as anti-diabetic and anti-inflammatory agents. The target compounds were also analysed for toxicity by in silico ADMET study and in vitro MTT assay on THP-1 and A549 cell lines. Thecoumarins enrichment process designed, was found specific for coumarins isolation as it resulted into 48.61% of total coumarins enrichment, which includes 31.2% marmelosin, 8.9% marmesin, 4% psoralen, 2% scopoletin, 1.7% umbelliferone, and 0.72% aegeline. The quantification with HPTLC and qNMR was found to be correlated with the HPLC assay results. The present study validates the potential use ofAegle marmelosas an anti-inflammatory and anti-diabetic agent. Coumarins enriched from the plant fruit have good therapeutic activity and can be used for Phytopharmaceutical ingredient development. The study is novel, in which coumarins were enriched and characterized by a simple and sophisticated methodology.
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