Current Pharmaceutical Biotechnology - Volume 20, Issue 11, 2019

Background and Objective: Chronic pain is a highly prevalent problem, involving high costs and seriously affecting a patient's quality of life. This review aimed to systematically review economic evaluations of pharmacological-based treatments for non-malignant chronic pain and to compare different treatment approaches with regard to their economic profile. Methods: PubMed and Scopus were systematically searched in April 2016. Studies were included if quality-adjusted life years and incremental cost-effectiveness ratios were reported. Quality assessment was carried out by using La Torre’s weighted scale on the Drummond checklist. Costs were converted into US$2014. Results: Fourteen economic evaluations met the inclusion criteria. Three treatment categories identified were: opioids, anticonvulsants, and anti-depressants. Compared to anticonvulsants and antidepressant, opioids had lower ICER. Transdermal buprenorphine showed an ICER of about US$11,000.00 while pregabalin showed an ICER of US$19,200. Studies included showed a diversity of methodological approaches, such as different modeling approaches and different perspectives (NHS and private payer). Conclusion: There are limitations to the success of making appropriate recommendations about which treatment is most cost-effective due to considerable variability between treatments, pain syndromes, and drug dosages. Opioids may have lower ICER, but the societal implications of the opioid epidemic and overdose deaths should be taken into account when coming to general conclusions about their cost-effectiveness. To ensure correct resource allocation as well as the best benefit for patients, uniform and standardized approaches of cost and outcome measurement in economic evaluations of chronic are needed.

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objectives: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/μl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/μl or PRP-R with 1.5·105 platelets/μl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

Objective: Calcium acetate (Ca(CH3COO)2) is commonly used in calcium supplement for medicine, which is used as an auxiliary agent to treat osteoporosis. An effervescent granule is widely used in medical industry due to its palatability. The purpose of this study is to develop a new preparation of compound effervescent granule of the biological calcium acetate (Ca(CH3COO)2 effervescent granule), overcoming the disadvantages of the previous other dosage forms of calcium and thus enhancing the therapeutic efficacy. Methods: The biological Ca(CH3COO)2 effervescent granule was prepared by the wet granulation method. The formulation was optimized by the orthogonal experiment. The effervescent base was comprised of various amounts of citric acid and sodium bicarbonate. Other ingredients were added for optimal performance of effervescent granule. The performed Ca(CH3COO)2 effervescent granule was evaluated for the particle size, repose angle, pH value of solution, calcium acetate content and effervescence time. The in vivo effects of Ca(CH3COO)2 effervescent granule on the bone microarchitecture were investigated via Micro-CT detection, and the serum calcium level was also investigated. Results: The optimized formulation of the biological Ca(CH3COO)2 effervescent granules was composed of calcium acetate, citric acid, sodium bicarbonate, PEG6000, aspartame, PVP ethanol solution, lactose and vitamin D. Our findings reveal that this biological Ca(CH3COO)2 effervescent granule exhibited prominent effect on preventing the bone-mass loss and did better in enhancing the bone microarchitecture compared to the other calcium preparations. Conclusion: The biological Ca(CH3COO)2 effervescent granule is a novel dosage form among so many kinds of calcium preparations. It may perform better functions in the dairy calcium supplement.

Background: Novel quercetin-loaded microparticles (QM) were fabricated using coaxial electrospraying, characterized for surface morphology and release profile, and evaluated for antitumor activity in vitro. Methods: QM exhibited an average diameter of 1.69 ±1.13 mm, which was an appropriate size suitable for respiratory delivery. X-ray diffraction patterns showed that the components in QM existed in an amorphous physical form, leading to favorable interactions between the drug (quercetin), the polymer matrix (polyvinylpyrrolidone, PVP) and other excipients (sodium dodecyl sulfate and sucralose). Results: QM performed much faster release rate compared with free quercetin powder (Q) in vitro. Furthermore, QM also showed more potent inhibitory effects on A549 cell growth with reduced cell viability, decreased cell migration and induced more G0/G1 phase cell cycle arrest than Q. Conclusion: Thus, the quercetin loaded microparticles exhibited more potent inhibitory effects than free quercetin on A549 cell. The increased antitumor activity could be attributed to the enhanced accumulation of quercetin in the A549 cells with the QM. However, further studies are necessary to elucidate the exact mechanisms.

Background: VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 are important proteins involved in the induction and development of a new blood vessel network through which the tumor is properly nourished and oxygenated. Objectives: The aim of the study was to evaluate changes in VEGF-A, VEGF-B, VEGFR-1 and VEGFR-2 expression in endometrial cancer depending on its grade and to determine the VEGFR-1 to VEGFR-2 concentration ratio. Methods: The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, Cracow, Poland). It included the one-way ANOVA and Tukey's post-hoc test (p<0.05). Results: Statistically significant differences in the level of VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 were observed between the majority of analyzed groups (except for VEGF-B; G3 vs. G1, p=0.997700). The expression pattern of VEGF-A, VEGF-R1, VEGFR-2 was as follows: G3>G2>G1>C; VEGF-B: G2> G3> G1>C. A lower concentration of VEGFR-1 than VEGFR-2 was found regardless of the cancer grade. Conclusion: VEGF-A, VEGF-B, VEGF-R1, VEGFR-2 are key proteins involved in tumor angiogenesis. The analysis of the entire panel of proteins participating in a given process is an important element of modern diagnostics. The concentration ratio of VEGFR-1 to VEGFR-2 appears to be a determining factor in the patients' survival prognosis.

Background: The study was conducted to identify the bacterial strain associated with marine sponge Hyrtiosaff. erectus collected from the Red Sea coastal water and to assess the utilization of their secondary metabolites for human benefit as antioxidant, anti-Alzheimer, anti-viral, anticancer and anti-inflammatory agent. Methods: After biochemical identification of Pesudomance sp. bacterial strain, the total polyphenol contents, cytotoxic, antioxidant, anti-Alzheimer, anti-viral, anticancer and anti-inflammatory activity of the Pesudomance sp. ethyl acetate extract were investigated by applying different biochemical assays. Polyphenol contents were investigated using spectrophotometric techniques. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), and 2,2/-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) ABTS radical scavenging activity assays. The cytotoxic effects were investigated by using the human cancerous cell lines. Results: The anti-Alzheimer, anti-viral, anticancer and anti-inflammatory activities were determined using ELISA. Qualitative phytochemical analysis of the Pesudomance sp. extract demonstrated the presence of a large and diverse group of substances such as alkaloids, carbohydrates, flavonoids, phenols, terpenoids, saponins, and tannins. The strong antioxidant activity of the Pesudomance sp. extract was mainly attributed to the protective role of polyphenols against reactive oxygen. It was also observed that Pesudomance sp. extract possessed significant anti-Alzheimer activity with 94% at 1 mg. The extract showed also high antiviral activity (90%) using reverse transcriptase enzymes inhibition assay. The examination of the anticancer activity by applying two experimental models, i.e., PTK and SHKI cleared out high significant percentages of 76.19 and 83.09 %; respectively. Conclusion: The anti-inflammatory profiling using TNF, COX1, COX2, IL6 also revealed high antiinflammatory activity with different metabolic pathway of 62.70, 75.444, 79.27 and 54.15 %; respectively. The present study concluded that ethyl acetate extract of Pesudomance sp. possessed strong antioxidant, anti-Alzheimer, and anti-viral, anticancer and anti-inflammatory activities. Further studies are required to purify the bioactive compounds.

Background: Kombucha beverage is considered as a dietary supplement and drinking it strengthens the body’s immune system which prevents diseases. Objective: The purpose of this study was to determine the amount of glucuronic acid and antibacterial activity of Kombucha black tea drink during its production at different storage temperature. Methods: The extent of glucuronic acid at temperatures of 20°C and 30°C was explored by the use of the HPLC system for 21 days. To analyse the antibacterial property, the influence of Kombucha black tea supernatant on the growth of Salmonella typhimurium, Staphylococcus aureus, and Lactobacillus rhamnosus bacteria was examined via the two procedures of the disc and agar well diffusion. Results: The production of glucuronic acid underwent a variation at 20°C from 17.0 mg/L on day 1 to roughly 27.2 mg/L on day 21, and the difference was significant. Furthermore, the quantity of this acid at 30°C increased from 42.2 mg/L on day 1 to 48.0 mg/L on day 21. The amount of glucuronic acid produced at 30°C was significantly greater than that at 20°C (p<0.05). This study indicated that the Kombucha black tea has antibacterial activity against Salmonella typhimurium and Staphylococcus aureus, but not against Lactobacillus rhamnosus. However, there are no statistical differences in antibacterial activity of Kombucha between incubation at 20oC and 30oC (P>0.05). Conclusion: This study offers a perspective on glucuronic acid production (especially in 30°C rather than 20°C) and antibacterial activity of Kombucha black tea beverage.