The Effect of Green Tea Consumption on Prostate Cancer Risk and Progression: A Systematic Review

This systematic review aimed to assess the clinical benefits of green tea consumption on the progression and prevention of prostate cancer (PCa). A systematic search was performed across the following databases: PubMed, Excerpta Medica dataBASE, Database of Abstracts of Reviews of Effects, Current Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. We included studies from database inception to September 2015. Studies must report on the effect of green tea consumption on PCa. The quality of observational studies was assessed using the Newcastle-Ottawa Scale (NOS), while randomized controlled trials (RCTs) were assessed for quality using the Jadad scale. A total of 15 articles were included, with 11 reporting on the effect of green tea consumption on PCa prevention, and four reporting on the effect of green tea on treatment. Mean NOS for observational studies was 7.4 (SD±1.3), with a range from 6 to 9, while all three RCTs scored 5 on the Jadad scale. Findings demonstrate that green tea appears to be an effective chemopreventive agent, particularly in those with high-grade prostate intraepithelial neoplasia. However, evidence of efficacy in the treatment of PCa is currently lacking. Given the limitations in current studies, more well-designed RCTs should be undertaken to determine if green tea indeed has a role in the prevention and treatment of PCa.     

Contraindications and side effects of commonly used medications in coronary CT angiography

For certain clinical applications, coronary CT angiography (CCTA) has become a useful tool for the noninvasive evaluation of coronary artery atherosclerosis. To optimize image quality in CCTA, medications are often given prior to scanning to slow the heart rate or distend the arteries. These medications have side effects and are contraindicated in certain patient populations. Metoprolol is the ß-blocker of choice in CCTA, and it has been shown to be effective in achieving the goal heart rate of less than 65 beats per minute for CCTA and in minimizing variability of heart rate. It is contraindicated in patients with hypotension or high degree AV block, and it must be used with caution in patients with asthma or obstructive pulmonary disease, patients with decompensated heart failure, and those with vasospastic or vasoocclusive disease. Diltiazem, the calcium channel blocker of choice in CCTA, is a reasonable alternative for heart control, particularly in patients with asthma or bronchospastic disease, and patients with orthotopic heart transplants that have been sympathetically denervated. Sublingual nitroglycerin is especially useful in order to dilate distal arteries to improve stenosis visibility. However, it is contraindicated in patients on erectile dysfunction medications and those with severe anemia. It must be used cautiously in patients with aortic stenosis or other preload-dependant cardiac pathologies.     

Optimization,in vitro release and toxicity evaluation of novel pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum semi-interpenetrating networks

BackgroundIn recent era, pH sensitive polymeric carriers that combines the materials engineering and medicine is gaining researcher’s attention as they maximizes drug concentration at site of absorption and reduces side effects for e.g. orally administered cetirizine HCl (CTZ HCl) upsets the stomach and furthermore shows high intestinal absorption. Thus, development of pH sensitive hydrogels with sufficient mechanical strength will be good candidate to address this issue.MethodsHere, we developed pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum (IA-g-poly(AM)/sterculia gum) semi-interpenetrating network (semi-IPN) by free radical polymerization technique for intestinal delivery of CTZ HCL.ResultsOptimized formulation (I5) with 6% w/w IA showed negligible swelling at pH 1.2, and maximum swelling at pH 7.4. Solid state characterization of optimized formulation showed successful development of semi-IPN structure and incorporation of drug without any noticeable drug-carrier interaction. In vitro release study showed biphasic pH dependent release of CTZ HCl, where initial burst release was observed at acidic pH followed by sustained release at basic pH. Acute oral toxicity and histopathological studies confirmed the non-toxic nature of IA-g-poly(AM)/sterculia gum.ConclusionConclusively, developed biocompatible semi-IPN hydrogels with sufficient pH sensitivity and mechanical strength could serve as a potential carrier for intestinal delivery of CTZ HCL to maximize its absorption and reduce side effects.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40199-021-00395-8.     

Optimization and In Vivo Evaluation of an Oral Dual Controlled-Release Tablet Dosage Form of Insulin and Duck Ovomucoid

The objectives of the present study were to (1) optimize the release rate of insulin from compressed microparticulates and (2) compare the in vivo hypoglycemic effect of optimized insulin microparticulates with compressed enzyme inhibitor (duck ovomucoid) and without inhibitor. A 3-factor, 15-run Box Behnken design was used to construct polynomial models correlating the dependent and independent variables. Independent processing variables were rate of addition of the alcoholic Eudragit© L100 dispersion, volume of the antisolvent, and compression pressure. Responses were cumulative percent of insulin released from 1–6 hours. Insulin and ovomucoid release was simultaneously analyzed by high-performance liquid chromatography. They demonstrated variable release rates, which were optimized to the Higuchi's square root of time model to release the insulin and the inhibitor over 6 hours. The relationship between dissolution profiles and process parameters were demonstrated by contour and response surface plots. In vivo hypoglycemic effect was evaluated in rabbits in a 3-way crossover design. Cocompressed microparticulates of insulin and duck ovomucoid displayed a 3.2-fold greater hypoglycemic effect when compared with a similar preparation without ovomucoid. This study demonstrated the potential benefits of dosage forms with dual controlled-release mechanisms for both the protein and enzyme inhibitor.     

Cyp1b1 protein in the mouse eye during development: an immunohistochemical study.

We show, for the first time, the spatiotemporal appearance of Cyp1b1 protein during mouse eye ontogeny. The protein was unambiguously identified in the adult mouse eye and newborn (P0) whole mouse microsomes and was shown to be localized in inner ciliary epithelium, corneal epithelium, retinal inner nuclear cells, and ganglion cells. The enzyme protein was present in the lens epithelium adjacent to the developing ciliary body at 15.5 days postconception (E15.5) and was most strongly expressed during E17.5 to 7 days postnatally (P07). Subsequently, it declined to very low levels. The protein was also expressed in the corneal endothelial cells adjacent to the ciliary body at P07. Cyp1b1 was barely detectable in the inner ciliary epithelium before E17.5 but increased rapidly postnatally, reaching adult levels by P28. Levels of the enzyme protein in the corneal epithelium were seen from E15.5 onward, increasing sharply, and after a decrease at P07, were highest in the adult animal eye. The presence of Cyp1b1 protein in the inner nuclear layer of the retina was very low in the prenatal eye, increasing rapidly postnatally, and was highest in the adult animal eye. In the ganglion cell layer of the retina, it increased slowly from E15.5 to P07 and then rapidly reached adult levels. Interestingly, Cyp1b1 was not detected in the trabecular meshwork at any stage of development or in the adult eye. We conclude that the enzyme may play important roles in normal eye development and function in mice as in humans, and that the mouse may prove to be an excellent model for determination of the roles of CYP1B1 in human eye development and function.     

Cardiovascular effects of the aqueous extract of Moringa pterygosperma

The aqueous extract of stem bark of Moriga pterygosperma (Family Moraingaceae) was investigated for its effect on various pharmacological parameters. In cardiovascular profile at lower concentrations (1–10 ng) it produced a dose dependent positive inotropic effect (n = 3, 1.29 ± 0.021 for 10 ng) and at higher concentrations (0.1–1 μg) a dose dependent negative inotropic effect (n = 3, 0.53 ± 0.033 for 1 μg) on the isolated frog heart. It also produced a dose dependent hypotensive effect on dog blood pressure (n = 3, 82 ± 0.98 for 20 mg/kg). It failed to elicit any effect on isolated guinea-pig ileum, rat stomach fundus or frog rectus abdominis muscle.     

Molecular genetics of primary congenital glaucoma in Brazil

PURPOSE: To determine the distribution of CYP1B1 gene mutations in Brazilian patients with primary congenital glaucoma (PCG). METHODS: PCG diagnosis was established by presence of buphthalmos in at least one affected eye and associated high intraocular pressures before the age of 3 years. CYP1B1 mutation screening of 52 patients with PCG was performed by SSCP and direct sequencing of PCR fragments. RESULTS: Eleven mutations, four of which are novel, were observed in 26 (50%) individuals. A new frameshift mutation (4340delG) was observed in 20.2% of all individuals screened. These individuals had early-onset, bilateral glaucoma that necessitated multiple surgical interventions. CYP1B1 mutations were twice as frequent in affected individuals of European descent as in individuals of African descent. Analysis of six intragenic single nucleotide polymorphisms (SNPs) established 5'-C-C-G-G-T-A-3' as the most common haplotype among the affected Brazilian individuals. A nonsense mutation (W57X) previously reported in an individual with Peters anomaly (compound heterozygote) was also observed in two individuals with PCG but combined with different mutations. A newly developed SSCP assay enabled us to detect all DNA mutations and polymorphisms previously detected by direct sequencing. CONCLUSIONS: Our results indicate that CYP1B1 mutations may be responsible for half of cases of PCG in the Brazilian population. The SNP haplotype 5'-C-C-G-G-T-A-3' was associated with the majority of CYP1B1 mutations. This haplotype harbors the high-activity V432 allele, which is emerging as a putative susceptibility factor in several cancers.     

Biodegradable poly(epsilon -caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen

To increase the local concentration of tamoxifen in estrogen receptor (ER) positive breast cancer, we have developed and characterized nanoparticle formulation using poly(epsilon -caprolactone) (PCL). The nanoparticles were prepared by solvent displacement method using acetone-water system. Particle size analysis, scanning electron microscopy, zeta potential measurements, and differential scanning calorimetry (DSC) were used for nanoparticle characterization. Biodegradation studies were performed in the presence and absence of Pseudomonas lipase in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. Tamoxifen loading over different concentrations was analyzed by high-performance liquid chromatography (HPLC) and the optimum loading concentration was determined. In vitro release studies were performed in 0.5% (w/v) sodium lauryl sulfate (SLS) containing PBS at 37 degrees C. Cellular uptake and distribution of fluorescent-labeled nanoparticles was examined in MCF-7 breast cancer cells. SEM micrographs and Coulter analysis showed nanoparticles with spherical shape and uniform size distribution (250-300 nm), respectively. Zeta potential analysis revealed a positive surface charge of +25 mV on the tamoxifen-loaded formulation. Being hydrophobic crystalline polyester, PCL did not degrade in PBS alone, but the degradation was enhanced by the presence of lipase. The maximum tamoxifen loading efficiency was 64%. Initial burst release of tamoxifen was observed, probably due to significant surface presence of the drug on the nanoparticles. A large fraction of the administered nanoparticle dose was taken up by MCF-7 cells through non-specific endocytosis. The nanoparticles were found in the perinuclear region after 1 h. Results of the study suggest that nanoparticle formulations of selective ER modulators, like tamoxifen, would provide increased therapeutic benefit by delivering the drug in the vicinity of the ER.