Prediction of 2-Year Carcinogenicity Study Results for Pharmaceutical Products: How Are We Doing?

Background: Oral squamous cell carcinoma (OSCC) is the most common oral cancer. In recent decades, numerous studies have focused on the effects of new herbal and natural bioactive substances or pharmaceutical products on different cancer types. Some investigations have shown that anthocyanins can inhibit carcinogenesis in various ways, and some others focused on the effects of anthocyanins on squamous cell carcinoma (SCC). Methods: An electronic search of the literature was carried out in PubMed, Web of Science, and Scopus databases using the keywords “anthocyanins” and “oral cancer” or “oral squamous cell carcinoma”. Articles relevant to our topic (except for review articles) were included in this study. Results: The reviewed articles showed the inhibitory and suppressive effects of anthocyanins on OSCC, which were exerted by inhibiting NF-κB, p-Akt/PI3k, and JAK/STAT3 pathways, the induction of caspase-1 and caspase-3 overexpression, pyroptosis, mitochondrial-mediated apoptosis, and reduction of expression and production of matrix metalloproteinases and urokinase-type plasminogen activator. Conclusions: Based on the results, the anti-proliferative and apoptotic effects of anthocyanins on OSCC were dominant. Their antimetastatic effect was also reported. Therefore, anthocyanins seem to be promising natural compounds for the prevention and treatment of OSCC. In vivo studies and clinical trials are recommended to further confirm these results.

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Style-shifting in Usage Instructions of Food, Beverage, and Pharmaceutical Products in Japanese Language

Japanese Research on Linguistics Literature and Culture ◽

10.33633/jr.v3i2.4589 ◽

2021 ◽

Vol 3 (2) ◽

pp. 100-112

Author(s):

Mulyadi Mulyadi ◽

Suhandano Suhandano ◽

Aris Munandar

Keyword(s):

Present Article ◽

Spoken Language ◽

Pharmaceutical Products ◽

Pharmaceutical Product ◽

External Factors ◽

Written Discourse ◽

Japanese Study ◽

Study Results ◽

The Status ◽

Style Shifting

The present article attempts to describe the shifting use of formal and informal styles in usage instruction discourse of food, beverage, and pharmaceutical products in Japanese. The aim is to explain the background of style-shifting from a formal style, indicated by -desu in adjectives and nouns and -masu in verbs, into an informal style without any -desu or –masu forms in place. The background is reviewed through the perspectives of both sociolinguistics and pragmatics. The data were collected from various food, beverage, and pharmaceutical product packages containing usage instructions in Japanese. Study results indicate that style-shifting does not only occur through spoken language (orally) but via written discourse, which maintains unchanging external factors or definite contexts. Style-shifting is not only affected by the status of the speech partner but also more likely affected by the content of the information delivered to the consumers. Aside from occurring within a single discourse, style-shifting is also observed at a narrower level, namely within one element of discourse conveying a relatively homogenous information.

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Pathogenesis of Renal Injury and Gene Expression Changes in the Male CD-1 Mouse Associated with Exposure to Empagliflozin

Toxicologic Pathology ◽

10.1177/0192623318784514 ◽

2018 ◽

Vol 46 (6) ◽

pp. 671-682 ◽

Cited By ~ 3

Author(s):

Brian Knight ◽

Jing Yuan ◽

Sally Koegler ◽

Parimal Pande ◽

Jennifer Hall ◽

...

Keyword(s):

Renal Injury ◽

Dose Group ◽

Glucose Transporter ◽

Transforming Growth Factor ◽

High Dose ◽

Sequencing Analysis ◽

Carcinogenicity Study ◽

Glucose Transporter 2 ◽

Study Results ◽

Renal Tubular

An increased incidence of renal tubular adenomas and carcinomas was identified in the 2-year CD-1 mouse carcinogenicity study with empagliflozin (sodium-glucose transporter 2 inhibitor) in high dose (1,000 mg/kg/day) male mice. A 13-week mouse renal investigative pathogenesis study was conducted with empagliflozin to evaluate dose dependency and temporal onset of nonneoplastic degenerative/regenerative renal tubular and molecular (genes, pathways) changes which precede neoplasia. Male and female CD-1 mice were given daily oral doses of 0, 100, 300, or 1,000 mg/kg/day (corresponding carcinogenicity study dose levels) for 1, 2, 4, 8, or 13 weeks. The maximum expected pharmacology with secondary osmotic diuresis was observed by week 1 at ≥100 mg/kg/day in both genders. Histopathologic kidney changes were first detected after 4 weeks of dosing in the male 1,000 mg/kg/day dose group, with progressive increases in the incidence and/or number of findings in this dose group so that they were more readily detected during weeks 8 and 13. Changes detected starting on week 4 consisted of minimal single-cell necrosis and minimal increases in mitotic figures. These changes persisted at an increased incidence at weeks 8 and 13 and were accompanied by minimal to mild tubular epithelial karyomegaly, minimal proximal convoluted tubular epithelial cell hyperplasia, and a corresponding increase in Ki-67-positive nuclei in epithelial cells of the proximal convoluted tubules. There were no corresponding changes in serum chemistry or urinalysis parameters indicative of any physiologically meaningful effect on renal function and thus these findings were not considered to be adverse. Similar changes were not identified in lower-dose groups in males nor were they present in females of any dose group. RNA-sequencing analysis revealed male mouse-specific changes in kidney over 13 weeks of dosing at 1,000 mg/kg/day. Treatment-related changes included genes and pathways related to p53-regulated cell cycle and proliferation, transforming growth factor β, oxidative stress, and renal injury and the number of genes with significant expression change dramatically increased at week 13. These treatment-related changes in genes and pathways were predominant in high-dose males and complemented the observed temporal renal tubular changes. Overall, these mouse investigative study results support the role of early empagliflozin-related degenerative/regenerative changes only observed in high-dose male CD-1 mice as a key contributing feature to a nongenotoxic mode of renal tumor pathogenesis.

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Studying Regional Clusters with the Use of Data Processing Systems: The Case of the Biopharmaceutical Cluster

REGIONOLOGY ◽

10.15507/2413-1407.110.028.202001.048-079 ◽

2020 ◽

Vol 28 (1) ◽

pp. 48-79

Author(s):

Tatiana Yu. Kudryavtseva ◽

Angi E. Skhvediani

Keyword(s):

Cluster Structure ◽

Pharmaceutical Products ◽

The State ◽

Economic Activities ◽

Cluster Development ◽

The Core ◽

Managerial Decisions ◽

Use Of Data ◽

Study Results ◽

Analytical System

Introduction. The dynamics of the development of the digital economy necessitates introduction of integrated information and analytical systems. This provides integration with the existing statistics for making managerial decisions in the field of public administration of cluster development in Russia. The objective of this study is to develop an information and analytical system, a database, and test it taking the case the biopharmaceutical cluster as an example. Materials and Methods. The study employed materials from the Clusters of Russia’s Regions database as well as statistical tools in accordance with the methodology proposed by the European Cluster Observatory. The tools used made it possible to calculate such factors as ‘coefficient of localization’, ‘size’ and ‘focus’; groups of Russian regions (stable, increasing, and decreasing ones) were identified depending on the state of the cluster under study. Results. Statistical databases containing the number of employees in the constituent entities of the Russian Federation for 2009–2018 have been formed and grouped in accordance with the structure of the core of the biopharmaceutical cluster. The core of the biopharmaceutical cluster includes two codes of the Russian National Classifier of Economic Activities: 24.4 – Manufacture of pharmaceutical products and 24.5 – Manufacture of soap; detergents, cleaning and polishing preparations; perfumes and cosmetic products. Regions of localization of biopharmaceutical clusters in Russia in 2009–2018 have been identified; corresponding cartograms have been developed. Discussion and Conclusion. The developed methodology enables quick monitoring of the concentration of employment in the regions and can be used to assess the effectiveness of managing the cluster development of the territory. The results of the study can be used by the authorities to substantiate the cluster industrial policy of the regions, as well as by researchers analyzing the state of the cluster structure of the regions, and by teachers implementing higher education programs in the field of Economic Geography and State and Municipal Administration.

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Assessing multiple sclerosis-related quality of life among Iranian patients using the MSQOL-54 tool: a cross-sectional study

BMC Neurology ◽

10.1186/s12883-021-02357-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shadi Ziaie ◽

Niloofar Namazi ◽

Golnaz Afzal ◽

Saghar Barati ◽

Rezvaneh Mohebbi ◽

...

Keyword(s):

Quality Of Life ◽

Multiple Sclerosis ◽

Cross Sectional Study ◽

Pharmaceutical Products ◽

Sectional Study ◽

Herbal Supplements ◽

Cross Sectional ◽

Supplement Use ◽

Study Results

Abstract Background Multiple sclerosis (MS) is a chronic autoimmune disease and is one of the most costly medical conditions that imposed families with catastrophic health expenditures. There is an increasing trend in using alternative medicines including, dietary supplements, herbs, vitamins, and minerals. To date, the association between dietary as well as herbal supplements and QoL in MS patients is under researched; thus, this study aimed to assess the association between the self-reported supplement used and QoL between MS patients. Methods This cross-sectional study was conducted on patients with MS referring to Shahid Kazemi Pharmacy, based in the city of Tehran, Iran, as a national pharmacy providing specialized pharmaceutical products and pharmaceutical care to patients. The Multiple Sclerosis Quality of Life-54 (MSQoL-54) tools was performed to evaluate MS patients QoL. Results A total number of 382 patients with MS participated in this study. They include 89 (23.3%) men and 293 (76.7%) women, aged 40 ± 10.9 years old. The overall score of the MSQoL-54 questionnaire was 41.58 out of 100. Physical health composite (PHC) and mental health composite (MHC) were 69.60 and 62.99 from 100, respectively. This study revealed that 76.4% of patients used at least one vitamin daily; 92.4% of patients do not receive any herbal product. Vitamin D is the most widely used supplement, followed by calcium, while vitamin C is the least consumed. No correlation was observed regarding supplement use and overall QoL, PHC, or MHC. There were no significant differences between QoL’s dimensions score in patients who used supplements. The results showed that increasing the number of supplements used did not relate to overall QoL, PHC, or MHC. In addition, there was not any correlation between the duration used of supplements and QoL’s dimensions score in MS patients (p-value> 0.05). Conclusions The dietary supplement appears to be popular among MS patients. The study results showed that the number of supplementations and their long-term use in patients with MS were not associated with higher QoL. Similarly, the herbal supplements have failed to improve QoL.

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Aesculin based glucosamine-6-phosphate synthase inhibitors as novel preservatives for food and pharmaceutical products: in-silico studies, antioxidant, antimicrobial and preservative efficacy evaluation

BMC Chemistry ◽

10.1186/s13065-021-00769-8 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Amit Lather ◽

Sunil Sharma ◽

Anurag Khatkar

Keyword(s):

Antimicrobial Activity ◽

Molecular Docking ◽

Side Effect ◽

Aloe Vera ◽

Pharmaceutical Products ◽

Stability Study ◽

Efficacy Evaluation ◽

Study Results ◽

In Silico Studies ◽

Phosphate Synthase

Abstract Background Presently available chemical based synthetic preservative have emerged with various side effects, so the aspiration of natural and side effect free novel preservative has been greatly increased. As the natural preservative exhibit poor side effect with improved preservative efficacy. The recent development in computational studies leads advancement in drug designing and discovery of novel glucosamine-6-phosphate synthase (G-6-P synthase) inhibition based natural antimicrobial preservatives. Here, selected aesculin derivatives were screened for G-6-P synthase inhibition via docking study and evaluated for antioxidant, antimicrobial, preservative efficacy as well stability study. Results Modified aesculin derivatives were designed, synthesized and showed potent G-6-P synthase inhibition with remarkable antimicrobial, antioxidant, preservative efficacy and stability study. The molecular docking with target pdb id 1moq from G-6-P synthase resulted with better dock score and energy for compound 1 as compared to standard drugs streptomycin, ciprofloxacin, ampicillin and fluconazole, that supported the wet lab results. Among the synthesized compounds, the compound 1 possessed good antioxidant activity as compared to standard L-ascorbic acid. The resultant data for antimicrobial activity of aesculin derivatives revealed compound 1 as the most potent antimicrobial compound as compared to the standard drugs streptomycin, ciprofloxacin, ampicillin and fluconazole. While compound 2 showed better antimicrobial activity as compared to streptomycin, ciprofloxacin, ampicillin. The preservative efficacy test for compound 1 in aloe vera juice and white lotion USP has been showed the log CFU/mL values within the prescribed limit of USP standard and results were comparable to standard sodium benzoate, ethyl paraben and propyl paraben. Compound 1 has been found to be within prescribed limit of stability study over six month. Conclusion Compound 1 showed the potent G-6-P synthase inhibitory, antioxidant, antimicrobial, preservative efficacy and stability study results as compared to standard drugs taken. The results have found comparable to molecular docking results, and this final compound may be used as new preservatives for food and pharmaceutical products. Moreover, the mechanistic insight into the docking poses was also explored by binding interactions of aesculin derivatives inside the pdb id 1moq. These results also supported the results for novel synthesized G-6-P synthase inhibitors. Graphical abstract

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Apportionment of Impairment from Meniscal Tears and Knee Arthritis

Guides Newsletter ◽

10.1001/amaguidesnewsletters.2013.sepoct01 ◽

2013 ◽

Vol 18 (5) ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Charles N. Brooks ◽

James B. Talmage

Keyword(s):

Medial Meniscus ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Detailed Knowledge ◽

Meniscal Tears ◽

Knee Arthritis ◽

Degenerative Arthritis ◽

Study Results ◽

Physical Findings ◽

Causation Analysis

Abstract Meniscal tears and osteoarthritis (osteoarthrosis, degenerative arthritis, or degenerative joint disease) are two of the most common conditions involving the knee. This article includes definitions of apportionment and causes; presents a case report of initial and recurrent tears of the medial meniscus plus osteoarthritis (OA) in the medial compartment of the knee; and addresses questions regarding apportionment. The authors, experienced impairment raters who are knowledgeable regarding the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), show that, when instructions on impairment rating are incomplete, unclear, or inconsistent, interrater reliability diminishes (different physicians may derive different impairment estimates). Accurate apportionment of impairment is a demanding task that requires detailed knowledge of causation for the conditions in question; the mechanisms of injury or extent of exposures; prior and current symptoms, functional status, physical findings, and clinical study results; and use of the appropriate edition of the AMA Guides. Sometimes the available data are incomplete, requiring the rating physician to make assumptions. However, if those assumptions are reasonable and consistent with the medical literature and facts of the case, if the causation analysis is plausible, and if the examiner follows impairment rating instructions in the AMA Guides (or at least uses a rational and hence defensible method when instructions are suboptimal), the resulting apportionment should be credible.

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Planned Home Births Safe, Study Results Suggest

Ob Gyn News ◽

10.1016/s0029-7437(05)70677-7 ◽

2005 ◽

Vol 40 (14) ◽

pp. 11

Author(s):

MICHELE G. SULLIVAN

Keyword(s):

Home Births ◽

Study Results

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Study Results Link Obesity and Asthma Severity

Pediatric News ◽

10.1016/s0031-398x(07)70256-4 ◽

2007 ◽

Vol 41 (4) ◽

pp. 44

Author(s):

DOUG BRUNK

Keyword(s):

Asthma Severity ◽

Study Results

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Efficacy of compression stockings in preventing post-thrombotic syndrome in patients with deep venous thrombosis: a systematic review and metaanalysis

VASA ◽

10.1024/0301-1526/a000508 ◽

2016 ◽

Vol 45 (2) ◽

pp. 141-147 ◽

Cited By ~ 7

Author(s):

Jakob Martin Burgstaller ◽

Johann Steurer ◽

Ulrike Held ◽

Beatrice Amann-Vesti

Keyword(s):

Systematic Review ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Cochrane Library ◽

Compression Stockings ◽

Post Thrombotic Syndrome ◽

Study Results ◽

Preventive Efficacy ◽

One Year ◽

The Cochrane Library

Abstract. Background: Here, we update an earlier systematic review on the preventive efficacy of active compression stockings in patients with diagnosed proximal deep venous thrombosis (DVT) by including the results of recently published trials. The aims are to synthesize the results of the original studies, and to identify details to explain heterogeneous results. Methods: We searched the Cochrane Library, PubMed, Scopus, and Medline for original studies that compared the preventive efficacy of active compression stockings with placebo or no compression stockings in patients with diagnosed proximal DVT. Only randomized controlled trials (RCTs) were included. Results: Five eligible RCTs with a total of 1393 patients (sample sizes ranged from 47 to 803 patients) were included. In three RCTs, patients started to wear compression stockings, placebo stockings or no stockings within the first three weeks after the diagnosis of DVT. The results of two RCTs indicate a statistically significant reduction in post-thrombotic syndrome (PTS) of 50% or more after two or more years. The result of one RCT shows no preventive effect of compression stockings at all. Due to the heterogeneity of the study results, we refrained from pooling the results of the RCTs. In a further RCT, randomization to groups with and without compression stockings took place six months after the diagnosis of DVT, and in another RCT, only patients with the absence of PTS one year after the diagnosis of DVT were analyzed. One RCT revealed a significant reduction in symptoms, whereas another RCT failed to show any benefit of using compression stockings. Conclusions: At this time, it does not seem to be justifiable to entirely abandon the recommendations regarding compression stockings to prevent PTS in patients with DVT. There is evidence favoring compression stockings, but there is also evidence showing no benefit of compression stockings.

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