Aim To evaluate the predictive significance of gene polymorphism in endothelin-1 type 2A receptor, NADPH oxidase, p53 protein, endothelial nitric oxide synthase, caspase 8, interleukin-1β, tumor ...necrosis factor-α, superoxide dismutase-2, glutathione peroxidase-1, β1-adrenoceptor, angiotensin-converting enzyme, and matrix metalloproteinase-3 (MMP-3) genes in evaluating the risk of anthracycline-induced cardiotoxicity (AIC) in women without concurrent cardiovascular diseases (CVD).Material and methods This study included 176 women aged 45.0 42.0; 50.0 years with breast cancer without concurrent CVD who were scheduled for polychemotherapy (PCT) with anthracycline antibiotics. Echocardiography was performed for all patients at baseline and at 12 months after the end of PCT course. Genetic polymorphism was determined with the polymerase chain reaction.Results At 12 months, all patients were in remission of the underlying disease. They were retrospectively included into 2 groups: 1st group, 52 patients with AIC and 2nd group, 124 women without AIC symptoms. The development of AIC was associated with the presence of the p53 protein gene Arg / Arg genotype (odds ratio (OR), 2.972; p=0.001), NOS3 gene T / T genotype (OR, 3.059; p=0.018), NADPH oxidase gene T / T genotype (OR, 2.753; p=0.008), GPX1 gene C / C genotype (OR, 2.345; p=0.007), MMP-3 gene 5A / 5A genotype (OR, 2.753; p=0.008), and ADRB1 gene G / G genotype (OR, 3.271; p=0.043).Conclusion Evaluation of genetic polymorphism in p53 protein (rs1042522), NOS3 (rs1799983), NADPH-oxidase (rs4673), GPX1 (rs1050450), ADRB1 (Arg389Gly, rs1801253), and MMP-3 (rs3025058) genes can be recommended for use prior to starting chemotherapy in women with breast cancer without CVD for assessing the risk of AIC. A maximum risk of cardiotoxicity is associated with the presence of the p53 protein gene Arg / Arg genotype and NOS3 gene T / T genotype.
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that removes various adducts from the 3' end of DNA. Such adducts are formed by enzymes that introduce single-strand breaks in DNA during ...catalysis (for example, topoisomerase 1) and a number of anticancer drugs with different mechanisms of action. Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes posttranslational modification (PARylation) of various targets and thus controls many cell processes, including DNA repair. Tdp1 is a PARP1 target, and its PARylation attracts Tdp1 to the site of DNA damage. Olaparib is a PARP1 inhibitor used in clinical practice to treat homologous recombination-deficient tumors. Olaparib inhibits PARylation and, therefore, DNA repair. The Tdp1 inhibitor OL7-43 was used in combination with olaparib to increase the antitumor effect of the latter. Olaparib cytotoxicity was found to increase in the presence of OL7-43 in vitro. OL7-43 did not exert a sensitizing effect, but showed its own antitumor and antimetastatic effects in Lewis and Krebs-2 carcinoma models.
Aim. To develop a visual aid “Comorbid patient Scale” and evaluate its effectiveness through dynamic follow-up of patients with chronic non-communicable diseases (NCDs) in outpatient ...practice.Materials and methods. The prevalence of risk factors and NCDs were analyzed in the course of a retrospective study of 1444 patients in rural areas. A visual aid “Comorbid Patient Scale” developed on obtained data has been evaluated in a 3-month prospective comparative study of 93 patients with NCDs, randomized to group 1, in which the Scale was used (n = 47), and a control group (group 2, n = 46).Results. Group 1 showed a statistically significant increase in adherence to treatment after using the Scale for 3 months: 81% vs 57% at baseline (p < 0.05); in group 2 similar indicators were: 61% vs 54% (the difference is not significant). In group 1, the proportion of smoking patients (39% vs 15% (p < 0.05)) and the number of patients with hypercholesterolemia (23% vs 0% (p < 0.05)) significantly decreased; the number of patients with well-controlled arterial hypertension increased from 47% to 87% (p < 0.05). A similar dynamics was observed in group 2, however, the difference was not statistically significant. At baseline and 3 months later, the share of patients without exacerbation of diseases of the musculoskeletal system and respiratory tract diseases was the same across the groups.Conclusion. The use of “Comorbid patient Scale” compared to standard patient management increases patient adherence to treatment by 17%, reduces the share of smoking patients by 21%, with hypercholesterolemia by 14%, with the achievement of target blood pressure indicators by 26%.
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that removes various adducts from the 3' end of DNA. Such adducts are formed by enzymes that introduce single-strand breaks in DNA during ...catalysis (for example, topoisomerase 1) and a number of anticancer drugs with different mechanisms of action. Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes posttranslational modification (PARylation) of various targets and thus controls many cell processes, including DNA repair. Tdp1 is a PARP1 target, and its PARylation attracts Tdp1 to the site of DNA damage. Olaparib is a PARP1 inhibitor used in clinical practice to treat homologous recombination-deficient tumors. Olaparib inhibits PARylation and, therefore, DNA repair. The Tdp1 inhibitor
OL7-43
was used in combination with olaparib to increase the antitumor effect of the latter. Olaparib cytotoxicity was found to increase in the presence of
OL7-43
in vitro. OL7-43 did not exert a sensitizing effect, but showed its own antitumor and antimetastatic effects in Lewis and Krebs-2 carcinoma models.
Aim.
To evaluate the role of polymorphisms in adrenoceptor beta 1 (
ADRB1
) (Arg389Gly, rs1801253) and angiotensin-converting enzyme (ACE) (I/D, rs4343) genes in assessing the effectiveness of ...β-blocker (carvedilol) and ACE inhibitor (enalapril) therapy in women with anthracycline-induced cardiotoxicity (AIC) without prior cardiovascular diseases (CVD) during 12-month follow-up.
Materials and methods.
A total of 82 women (average age 45.0 (42.0; 50.0) years) with AIC and without prior CVD were included in the study. Echocardiography was performed and serum levels of NT-proBNP were determined at baseline and at 12 months after the enrollment. Gene polymorphisms in
ADRB1
and
ACE
genes were evaluated by polymerase chain reaction at baseline.
Results.
Carriers of the G/G genotype in the
ADRB1
gene and G/G genotype in the
ACE
(I/D, rs4343) gene showed a significant increase in left ventricular ejection fraction (LVEF), a decrease in the size of the left ventricle (LV) and left atrium (LA), and a fall in the NT-proBNP level. Carriers of other genotypes had further progression of AIC which was manifested through a decrease in LVEF and an increase in the size of LV and LA.
Conclusion.
Evaluation of gene polymorphisms in
ADRB1
(Arg389Gly, rs1801253) and
ACE
(I/D, rs4343) genes may be recommended before treatment initiation for AIC in women without prior CVD to determine who will benefit from carvedilol and enalapril therapy, as well as to identify a priority group of patients for personalized intensification and optimization of treatment for decreasing development of adverse cardiovascular events.
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•Albumin performs structural, enzymatic and transport functions in vivo.•We studied albumin complexes with H2T((4-N+MePy)I−)4P in aqueous solvents.•Determined that the stability ...constant of the porphyrin complexes with albumin.•The porphyrin is localized within the subdomains IB and IIA protein.
In present work interactions of bovine serum albumin with 5,10,15,20-tetrakis(4-N-methylpyridil) tetra iodide porphyrin have been studied by electron absorption and fluorescence spectroscopy. The studies were carried out in aqueous media at different pH and in water–dimethylformamide mixtures containing up to 0.19M of the organic solvent. It has been demonstrated that the porphyrin forms stable complexes with BSA in which the porphyrin is located subdomains IB and IIA. The stability constants of the complexes is practically independent of pH.
Purposeful development of special methods to be included into pharmacopoeial monographs on the quality of darunavir (DRV) preparations is shown to allow the use of expensive imported standard samples ...(SSs) for drug analysis to be avoided. Part I of the present work describes these methods and their validation. UV spectrophotometry is proposed in the “Authenticity” section for detecting DRV by the coincidence of extrema in the spectrum of an aqueous MeOH extract (pH 9) with well-known peaks in the spectrum of deprotonated DRV at 230 nm (minimum) and 267 nm (maximum). This section also requires GC analysis for solvated EtOH, the presence of which indicates that DRV ethanolate was used as the active pharmaceutical ingredient (API) and the absence of which, that non-solvated amorphous DRV was used. The significant increase in the accuracy of the quantitative determination and the sharp reduction in its duration allow the use of SSs to be avoided. For this reason, the “Dissolution” section proposes determining the DRV concentration in the dissolution medium (pH 3) by spectrophotometry using a method that requires experimental determination of the specific absorption coefficient
A
1
cm
1
%
of DRV solutions in this medium at the maximum (267 nm). The established value
A
1
cm
1
%
= (393.4 ± 2) cm
–1
was a physicochemical constant with a relative standard deviation
RSD
< 1% at confidence level α = 0.05.
BACKGROUND:Underrepresentation of ethnic minority communities limits the generalizability of HIV vaccine trial results. We explored perceived barriers and motivators regarding HIV vaccine trial ...participation among low-socioeconomic ethnic minority respondents at risk for HIV.
METHODS:Six focus group interviews were conducted using a semistructured interview guide. Participants (N = 58, mean age = 36 years, 37% female, and 56% Latino/a and 35% African American) were recruited using venue-based sampling in Los Angeles. Data were analyzed using narrative thematic analysis and Ethnograph qualitative software.
RESULTS:Perceived barriers to HIV vaccine trial participation, in rank order, were (1) vaccine-induced HIV infection, (2) physical side effects, (3) uncertainty about vaccine efficacy, (4) uncertainty about other vaccine characteristics, (5) mistrust, (6) low perceived HIV risk, (7) study demands, (8) stigma, and (9) vaccine-induced HIV seropositivity. Motivators were (1) protection against HIV infection, (2) free insurance and/or medical care, (3) altruism, and (4) monetary incentives.
CONCLUSIONS:Population-specific HIV vaccine trial recruitment and implementation strategies should address trial risks from a family perspective, cultural gender norms, mistrust, low perceived HIV risk, the importance of African-American and Latino/a community participation in HIV vaccine trials, and misconceptions about gaining protection against HIV infection. Increasing the cultural relevance of trial recruitment and implementation should facilitate the participation of Latinos/as and African Americans in HIV vaccine trials.
Liquefied hydrocarbon mixtures with traceable composition are required in order to underpin measurements of the composition and other physical properties of LPG (liquefied petroleum gas), thus ...meeting the needs of an increasingly large industrial market.
This comparison aims to assess the analytical capabilities of laboratories for measuring the composition of a Liquid Petroleum Gas (LPG) mixture when sampled in the liquid phase from a Constant Pressure Cylinder. Mixtures contained ethane, propane, propene, i-butane, n-butane, but-1-ene and i-pentane with nominal amount fractions of 2, 71, 9, 4, 10, 3 and 1 cmol mol
−1
respectively.
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The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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