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SUMMARY: Estradiol and progesterone receptors play an essential role in the changes occurring in the uterus during the estrus cycle in dogs (Canis lupus familiaris). In order to investigate the potential effect of progestational agent medroxyprogesterone acetate (MPA) when is used during anestrus on the expression of estradiol receptors [ER], progesterone receptors [PR] and nuclear protein Ki67, we evaluated uterine tissue immunohistochemically. Uteri were grouped as nulliparous (control, n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount and location of PR, ER and Ki67 were studied on the epithelial surface, apical and basal regions of the endometrium and myometrium using immunohistochemical techniques with a spectral confocal microscope and analyzed by ANOVA. Differences in ER were observed between the multiparous and MPA-treated groups in the apical region of the endometrium (p=0.0022). Differences in cell proliferation were detected between the nulliparous and multiparous groups (p=0.0037) and nulliparous and MPA-treated groups (p=0.0003) in the basal region of the endometrium. In conclusion, two doses of MPA (5mg/kg; i.m.) do not have a significant effect on the expression of ER and PR; however, they inhibit cell proliferation in the basal region of the endometrium, which includes the stroma, subepithelial cell layer, compact layer, and spongy layer. The clinical and long-term effect of this treatment should be evaluated in subsequent studies.
Los receptores de estradiol y progesterona juegan un rol fundamental en los cambios que se producen en el útero durante el ciclo estral de las perras (Canis lupus familiaris). El objetivo de este estudio fue evaluar las expresiones de ER-a y PR en el útero y la proliferación de células endometriales detectando la expresión nuclear de la proteína Ki67 en perras expuestas a la progestina sintética MPA y compararlas con perras nulíparas y multíparas expuestas a progesterona luteal. Úteros fueron agrupados como nulíparas (control, n=11), multíparas (n=11) y tratadas con MPA (n=11; nulíparas con dos tratamientos; 5 mg/kg; i.m.). La expresión de PR, ER-a y Ki67 fue evaluada en la regiones apicales y basales del endometrio y miometrio con un microscopio confocal espectral. Se observó diferencias en ER-a entre los grupos multíparas y tratados con MPA en la región apical del endometrio (p=0,0022). Se detectaron diferencias en la proliferación celular entre los grupos de nulíparas y multíparas (p=0,0037) y los grupos de nulíparas y tratados con MPA (p=0,0003) en la región basal del endometrio. En conclusión, dos dosis de MPA (5mg/kg; i.m.) no tienen un efecto significativo sobre la expresión de ER y PR; sin embargo, inhiben la proliferación celular en la región basal del endometrio, el cual incluye a estroma, capa de células subepiteliales, estratos compacto y esponjoso. El efecto clínico a largo plazo de este tratamiento debe ser evaluado en estudios posteriores.
Subject(s)
Animals , Female , Dogs , Progesterone/metabolism , Uterus/metabolism , Receptors, Estrogen/metabolism , Ki-67 Antigen/metabolism , Immunohistochemistry , Medroxyprogesterone Acetate/metabolismABSTRACT
Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.
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Background: Contraception is the intentional use of artificial methods or other techniques to prevent pregnancy as a consequence of sexual intercourse. Progesterone only injectables are highly effective in preventing in pregnancy as they do not rely on daily usage of contraceptions as such as oral contraceptive pills and barrier methods. Injection depot-medroxyprogesterone acetate (DMPA) is an effective contraceptive method in lactating mother and postabortal patients. Aims and Objectives: The aims of this study were to study utilization pattern, acceptance, effectiveness, and adverse effects of DMPA in postpartum and postabortal women. Materials and Methods: It was a prospective and observational single-center study and was conducted at tertiary care teaching hospital. The data were collected in patient received Inj. DMPA 150 mg intra muscularly immediately after abortion and delivery before discharge. The follow-up was done after administration of DMPA (usually every 3 months). Results: In this study, 56 (53.34%) patients were in the age group of 18–25 years, while 38 (36.19%) patients were 26–35 years whereas 11 (10.47%) were more than 36 years. Out of 105 patients, 12 patients were administered only one injection, 16 patients administered two injections and 16 patients given three injections of DMPA. Common adverse effects of DMPA are irregular bleeding (43.8%), amenorrhea (22.8%), and heavy bleeding (5.7%). Out of 24 patient who developed amenorrhea after injections of DMPA, total 11 patients had amenorrhea after fourth injection, 5 patients after first injection, and 2 patients after second injection of DMPA. Average time for return of fertility after last injection of DMPA was 9 months. Conclusion: DMPA is very effective contraceptive and apart from menstrual troubles that there are no significant major side (weight gain, mood changes, etc.) effects related to its use. DMPA may cause a delay in the return of fertility, the return of fertility takes 7–10 months from date of last injection, but it is completely reversible.
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Objective: To investigate the specificity of endogenous metabolic profile in plasma of patients with occupational acute methyl acetate poisoning using non-targeted metabolomics. Methods: A total of six patients with occupational acute methyl acetate poisoning were selected as the poisoning group, while 10 healthy workers without occupational exposure history of chemical hazards in the same industry were selected as the control group using the judgment sampling method. Metabolites in patient plasma of the two groups were detected using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and non-targeted metabolomics analysis was performed. Principal component analysis and partial least squares discriminant analysis were used to identify differential metabolites and analyze their metabolic pathways. Results: There were significant differences in metabolite profiles in patient plasma between poisoning group and control group. A total of 195 differentially expressed metabolites were screened in plasma of patients in poisoning group, including 119 upregulated and 76 downregulated metabolites. Lipid substances (lipids and lipid-like molecules) accounted for the highest proportion (21.5%). The differential metabolites of poisoning group were related to folate biosynthesis, amino acid metabolism, pyrimidine metabolism, sphingolipid biosynthesis and other metabolic pathways in plasma compared with the control group (all P<0.05). Conclusion: Occupational acute methyl acetate poisoning affects metabolism of the body. The folic acid biosynthesis, amino acid and lipid metabolism and other pathways may be involved in the occurrence and development of poisoning.
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Objective:To compare the effect and biotoxicity of tert-butyl acetate (TBA) and ethyl butyrate (EB) on stone dissolution in vitro.Methods:Ten gallstone samples from patients with multiple gallbladder stones were selected and the cholesterol content was analyzed by HPLC. Stone dissolution tests of TBA and EB were performed on cholesterol gallstone in vitro, and the weight of stone at each time point was recorded, meanwhile, methyl tert-butyl ether (MTBE) was used as the control. The inhibitory effects of MTBE, TBA and EB on proliferation of human normal liver cell line LO2 were analyzed by cell proliferation inhibition assay. Flow cytometry was used to analyze the effects of MTBE, TBA and EB on the early and late apoptosis of LO2 cells, and the changes of reactive oxygen species level in LO2 cells were also analyzed.Results:Of the 10 gallbladder gallstones, 6 were cholesterol gallstones and 4 were non-cholesterol gallstones. Stone dissolution experiment showed that the remaining stones of MTBE, TBA and EB groups were (47.83±3.84)%, (58.12±4.53)% and (75.75±4.61)% 30 minutes later. The remaining stones were (18.38±6.47)%, (33.82±6.22)% and (56.38±3.91)% 90 minutes later. MTBE had the best stone dissolution effect in vitro, the stone dissolution effect of TBA was slightly weaker than MTBE, and the stone dissolution effect of EB was relatively weak in all ( P<0.05). The cell proliferation inhibition experiment showed that the cell viability of the control group, MTBE group and TBA group were (100.00±4.46)%, (96.79±4.32)% and (93.72±3.51)%, respectively, and there were no significant differences among the three groups ( P>0.05). However, the cell viability of EB group (87.57±5.29)% was lower than the above three groups, and the differences were statistically significant ( P<0.001). The early apoptosis and late apoptosis of the control group were (1.67±0.15)% and (1.27±0.06)%, respectively. EB induced early apoptosis (15.90±0.53)% ( P<0.001) and late apoptosis (5.13±0.76)% ( P<0.05). However, MTBE and TBA had no significant effect on cell apoptosis ( P>0.05). Compared with control group, MTBE, TBA and EB all significantly inhibited the level of reactive oxygen species ( P<0.05), and the inhibitory effect of EB was the most obvious. Conclusions:TBA has good stone dissolution effect and biosafety for gallbladder cholesterol stones in vitro, while EB has relatively poor performance. TBA is a potential drug for gallstone dissolution.
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Objective:To investigate the effects of fractional CO 2 laser, focused ultrasound and simple drug treatment of gynecological vulva white lesions. Methods:A prospective study was conducted on 126 patients with white lesions of the vulva admitted to Hainan Cancer Hospital from August 2018 to December 2020. They were divided into drug group, focused ultrasound group and fractional CO 2 laser group by random number table method, with 42 patients in each group. The drug group was treated with mometasone furoate cream or dexamethasone acetate cream, and the focused ultrasound group was treated with focused ultrasound; the fractional CO 2 laser group was treated with fractional CO 2 laser. The serum interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and human epidermal growth factor (EGF) levels before and after treatment, and Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI) scores of the three groups were compared. Results:Before treatment, there was no significant difference in the levels of IL-2, TNF-α, CRP and EGF among the three groups (all P>0.05). After treatment, the levels of IL-2, TNF-α, CRP and EGF in the three groups were significantly decreased, and the levels of IL-2, TNF-α, CRP and EGF in the focused ultrasound group and fractional CO 2 laser group were lower than those in the drug group, with statistically significant difference (all P<0.05). Before treatment, there was no significant difference in the white lesions, dry pruritus, sexual pain and chapped skin scores of the three groups (all P>0.05); After treatment, scores of all dimensions of the three groups were significantly decreased, and scores of all dimensions of the focused ultrasound group and fractional CO 2 laser were lower than those of the drug group, with statistical significance (all P<0.05). Before treatment, there was no significant difference in the scores of symptoms and feelings, daily activities and interpersonal relationship of the three groups (all P>0.05); After treatment, scores of all dimensions of the three groups were significantly decreased, and scores of all dimensions of the focused ultrasound group and fractional CO 2 laser were lower than those of the drug group, with statistical significance (all P<0.05). Conclusions:Fractional CO 2 laser has a remarkable effect in the treatment of gynecological vulva white lesions, which can reduce the level of inflammatory factors in patients, improve the pain condition, and improve the quality of life.
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@#In order to study the involatile chemical components in Moutai-flavored distiller’s grains, the Moutai-flavored distiller’s grains were extracted with 75% ethanol, followed by extraction with petroleum ether, ethyl acetate, and n-butanol. Silica gel, ODS, sephadex LH-20, and preparative HPLC were used to separate and identify the petroleum ether and ethyl acetate layers.ESI-MS and NMR were used to identify the compounds, which were respectively identified as pentadecanoic acid (1), palmitic acid (2), trans-2-decenoic acid (3), n-nonyl octadecanoate (4), ethyl octadecanoate (5), ethyl linoleate (6), luric acid (7), 1, 3-dicaprylyl-2-linoleylglycerin (8), cyclic (phenylalanine-proline) (9), cyclo-(proline-leucine) (10), 3, 6-bis-(2-methylpropyl)-2,5-dione piperazine (11), 4-hydroxyphenethyl alcohol (12), 2,4-dihydroxybenzoic acid (13), stigmasterol (14), 2-furancarboxylic acid (15), valine (16), L-alanine acyl-L-proline (17), dihydroquercetin (18), 5, 7, 3'', 4''-tetrahydroxyflavonoids (19), quercetin (20), and naringenin (21). Compounds 1-21 were isolated from distiller’s grains for the first time.
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Objective To detect and analyze the susceptibility genes of methyl acetate poisoning in patients by whole exome sequencing. Methods Two patients with occupational acute severe methyl acetate poisoning and their first-degree relatives who work in the same occupation and position with similar working hours were selected as the research subjects by judgment sampling method. Peripheral blood was collected for whole exome sequencing. The sequencing data was compared with the public genome database to screen the mutation sites and find out the gene sites related to methyl acetate poisoning. The suspected pathogenic mutation genes were annotated and interpreted. Results The results of whole exome sequencing showed that there were 40 differential genes between the patients with methyl acetate poisoning and their first-degree relatives, including 80 single nucleotide polymorphisms and eight Indel with specific marker sequence index. Among these, the genes with strong correlation were carboxyesterase 1 (CES1) and mucin (MUC) 5B. The CES1 gene loci c.248C>T (p.Ser83Leu) heterozygous mutations, MUC5B gene loci c.6635C>T (p.Thr2212Met) and c.7685C>T (p.Thr2562Met) heterozygous mutations in patients with methyl acetate poisoning were detected. They were missense mutations. By constructing a protein-protein interaction network, a total of 11 pairs of interactions with high levels of evidence were identified, involving genes such as lysine methyltransferase 2C, HECT and RLD domains containing E3 ubiquitin protein ligase 2, neutrophil cytoplasmic factor 1, nicotinamide adenine dinucleotide phosphate oxidase 3, C-terminal binding protein 2, zinc finger protein 717, FSHD region gene 2 family member C, FSHD region gene 1, MUC4, MUC6, MUC5B, and MUC12. Conclusion The polymorphism of CES1 and MUC5B genes may be related to the occurrence and development of methyl acetate poisoning in patients.
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AIM: To assess the bioequivalence of oral dexamethasone acetate tablets between the test and reference formulations in healthy adult Chinese subjects on an empty stomach and after meals. METHODS: A randomized, open, single-dose, two-cycle double crossover bioequivalence study was followed. Twenty-four healthy subjects were included in the fasting group, and 32 healthy subjects were included in the postprandial group, taking 2 tablets (0.75 mg/tablet) of the test formulation (T) or 3 tablets (0.50 mg/tablet) of the reference formulation (R) per cycle for two cycles. The concentrations of dexamethasone acetate in human plasma were determined using liquid chromatography-mass spectrometry, and the pharmacokinetic parameters were calculated according to the non-atrial model using WinNonlin 8.0 software.The bioequivalence of both the test formulation and the reference formulation was evaluated. RESULTS: The pharmacokinetic parameters after oral administration of dexamethasone acetate tablets in a fasted state in subjects with the reference formulation are as follows: Tmax 1.13 (0.50, 4.00) and 1.00 (0.50, 5.00) h, AUC0-t (72.25±21.55) and (69.23±17.76) ng · mL
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Females increase aggression for mating opportunities and for acquiring reproductive resources. Although the close relationship between female aggression and mating status is widely appreciated, whether and how female aggression is regulated by mating-related cues remains poorly understood. Here we report an interesting observation that Drosophila virgin females initiate high-frequency attacks toward mated females. We identify 11-cis-vaccenyl acetate (cVA), a male-derived pheromone transferred to females during mating, which promotes virgin female aggression. We subsequently reveal a cVA-responsive neural circuit consisting of four orders of neurons, including Or67d, DA1, aSP-g, and pC1 neurons, that mediate cVA-induced virgin female aggression. We also determine that aSP-g neurons release acetylcholine (ACh) to excite pC1 neurons via the nicotinic ACh receptor nAChRα7. Together, beyond revealing cVA as a mating-related inducer of virgin female aggression, our results identify a neural circuit linking the chemosensory perception of mating-related cues to aggressive behavior in Drosophila females.
Subject(s)
Animals , Male , Female , Drosophila/physiology , Drosophila Proteins/physiology , Cues , Sexual Behavior, Animal/physiology , Aggression/physiology , Drosophila melanogaster/physiologyABSTRACT
Background Lead is widely distributed. Lead exposure interferes with early life development in zebrafish, but the mechanisms by which lead exposure affects skeletal development and cardiac development are not clear as yet. Objective To investigate the molecular mechanisms of bone development and cardiac development toxicity induced by lead acetate exposure. Methods Zebrafish embryos were exposed to different concentrations of lead acetate (0, 6, 12, 24, and 48 μmol·L−1) for 3 h post-fertilization (3 hpf) until 5 d post-fertilization (5 dpf). The malformation phenotypes of 5 dpf were counted, and the mRNA expressions of spinal development-related genes (bmp2b, bmp4, bmp9, runx2a, runx2b) and heart development-related genes (nkx2.5, myh6, myh7) were detected by quantitative PCR (qPCR). Expressions of genes of development-related regulatory pathways including Wnt/β-catenin pathway (wnt5a, wnt8a, wnt10a, β-catenin) and TGF-β pathway (tgf-β1, tgf-β2) as well as key molecule eph of Eph-Ephrin signaling were analyzed. Results At 5 dpf, the zebrafish in the lead acetate treated groups showed deformed phenotypes including spinal curvature and pericardial sac edema compared to the control group. In the lead acetate groups at 24 and 48 μmol·L−1, the spinal curvature deformity rates reached 26.47% and 71.52% (P<0.01) respectively. The qPCR results revealed that the expression levels of spinal development-related genes bmp2b, bmp4, bmp9, runx2a, and runx2b were downregulated in the 48 μmol·L−1 exposure group compared to the control group by 82.8%, 58.0%, 88.7%, 85.5%, and 69.2%, respectively (P<0.05 or P<0.01); the expression levels of heart development-related genes myh6, myh7, and nkx2.5 were down-regulated by 63.7%, 58.9%, and 55.2%, respectively (P<0.01); the expression levels of wnt8a and β-catenin in the Wnt/β-catenin pathway were down-regulated by 71.5% and 47.3% (P < 0.05 or P < 0.01), respectively; the expression level of tgf- β1 in the TGF-β pathway was down-regulated by 67.5% (P<0.01); the expression level of eph was down-regulated by 86.9% (P<0.01). Conclusion Lead acetate exerts developmental toxic effects on zebrafish heart and bone by down-regulating the expressions of genes related to spinal development and heart development, as well as inhibiting development-related Wnt/β-catenin and TGF-β pathways and Eph-Ephrin signaling, causing malformed phenotypes such as spinal curvature and pericardial sac edema.
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This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.
Subject(s)
Antioxidants/chemistry , Molecular Docking Simulation , Artemisia , Network Pharmacology , Phosphatidylinositol 3-Kinases , Anti-Inflammatory Agents/chemistry , Drugs, Chinese Herbal/pharmacology , Interleukin-6ABSTRACT
Acetato de Megestrol (AM). Indicação: Tratamento da Síndrome anorexia-caquexia (SAC) em doentes crônicos em fase de cuidados paliativos. Objetivo: Avaliar a eficácia e segurança do uso do AM em doentes crônicos sob cuidados paliativos. Métodos: Foi realizada uma revisão rápida de revisões sistemáticas, com levantamento bibliográfico nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library, Web Of Science e em registros de revisões sistemáticas e ensaios clínicos. A qualidade metodológica dos estudos incluídos foi avaliada com a ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: A busca recuperou um total de 2.370 após exclusão das duplicatas; 1003 estudos foram triados pelo título e resumo, de acordo com os critérios de inclusão previamente estabelecidos. Dezesseis RSs foram selecionadas para leitura completa, sendo que, destas, apenas 1 RS foi classificado com alta qualidade metodológica. Após a análise dos ECR das RSs excluídas, um ECR foi incluído considerando os critérios de inclusão. Dois estudos adicionais publicados posteriormente a RS de Ruiz-Garcia et al. Conclusão: Com base nas evidências disponíveis, o AM proporciona leve ganho de peso e melhora o apetite, porém esses resultados não refletem melhoria na qualidade de vida dos pacientes, além de haver risco considerável de desenvolver fenômenos tromboembólicos
Megestrol acetate (MA). Indication: treatment of anorexia-cachexia syndrome (ACS) in chronic diseases patients, under palliative care. Objective: Evaluate the efficacy and safety of the use of Megestrol Acetate to treat ACS in patients under palliative care. Methods: Rapid review protocol of Systematic Reviews and Clinical Trials. A literature Search was performed in PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library, Web of Science databases and in clinical trials records, following a predefined strategy. The methodological quality of the selected articles was assessed through AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2) tool. Results: the search resulted in 2,370 articles, after the duplicates exclusion. 1003 were analyzed by tittle and abstracts according the inclusion criteria. 16 were selected for full text reading, and only one considered to have high methodological quality. After the analyses of the Randomized Clinical Trials of the excluded Systematic Reviews, one RCT was included. Two additional studies published after the SR of Ruiz-Garcia et al were also included. Conclusion: based on available evidence, the MA promoted a small gain in body weight and a slight appetite improvement, although these results did not imply an enhancement in their quality of life. Moreover, there is a considerable risk of causing thromboembolic disorders
Subject(s)
Humans , Male , Female , Megestrol Acetate/adverse effects , Weight Gain/drug effectsABSTRACT
The safety and survival benefits of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer have been confirmed by randomized controlled trials and clinical studies abroad. However, real-world studies remain lacking. In this article, we review the progress of real-world studies of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer and the problems faced in clinical practice against the background of differentiated real-world studies. Further research is needed to address clinically important issues, such as individualized dosing, combination dosing, and monitoring of adverse effects.
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OBJECTIVE@#To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism.@*METHODS@#The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT.@*RESULTS@#Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G1 phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells.@*CONCLUSION@#TPA induces NB4 cell cycle arrest in G1 phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
Subject(s)
Humans , Leukemia, Promyelocytic, Acute , Caspase 3/metabolism , Caspase 9/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , bcl-2-Associated X Protein/metabolism , Cell Line, Tumor , Cell Division , Apoptosis , RNA, Messenger , Cell ProliferationABSTRACT
En algunos estudios se ha asociado a la terapia de reemplazo hormonal (TRH) con estrógenos y progestinas a un mayor riesgo de cáncer de mama que la terapia con estrógenos solos. Sin embargo, dependiendo de su naturaleza algunas progestinas serían más seguras que otras. Se buscaron y analizaron artículos atingentes al tema en las bases de datos Google Scholar, PubMed, Science, SciELO y Cochrane, introduciendo los siguientes términos: terapia de reemplazo hormonal y cáncer de mama, progestinas y cáncer de mama, receptor de progesterona. Específicamente se ha asociado a las progestinas sintéticas acetato de medroxiprogesterona, noretisterona y levonorgestrel con un mayor riesgo de cáncer de mama, no así a la progesterona natural, a la progesterona oral micronizada ni a la didrogesterona. La progesterona natural, progesterona micronizada y didrogesterona serían más seguras en TRH para evitar el desarrollo de cáncer de mama, lo que estaría dado por la mayor especificidad en su acción.
In some studies, hormone replacement therapy (HRT) with estrogens and progestins has been associated with a higher risk of breast cancer than therapy with estrogens alone. However, depending on their nature, some progestins may be safer than others. This article analyzes the mode of action of progesterone in breast tissue and also the role of some progestins in the development of this pathology. Articles related to the subject were searched for and analyzed in Google Scholar, PubMed, Science, SciELO and Cochrane databases, introducing the following terms: hormone replacement therapy and breast cancer, progestins and breast cancer, progesterone receptor. Specifically, synthetic progestins medroxyprogesterone acetate, norethisterone, and levonorgestrel have been associated with an increased risk of breast cancer, but not natural progesterone, micronized oral progesterone, or dydrogesterone. Natural progesterone, micronized progesterone and dydrogesterone would be safer in HRT to prevent the development of breast cancer, which would be due to the greater specificity of their action.
Subject(s)
Humans , Female , Progestins/adverse effects , Breast Neoplasms/chemically induced , Progestins/classification , Progestins/physiology , Receptors, Progesterone , Risk Assessment , Hormone Replacement Therapy/adverse effects , Estrogens/adverse effectsABSTRACT
This study was carried out on ?sh channa punctatus to investigate the lethal concentration of copper acetate on ?sh channa punctatus at 48 hr. Experiment procedure was repeated ?ve times at the selected copper acetate concentrations, noting the number of ?sh killed. The mean values was taken. These values was taken to determine LC50 value for 48 hr. By Dragstedt and Behrens Method
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RESUMEN Fundamento: La electroforesis de proteínas y las cadenas ligeras libres en suero son técnicas utilizadas en el diagnóstico del mieloma múltiple. Sin embargo, la utilidad diagnóstica de ambas pruebas puede variar según el método empleado y condiciones reales del medio donde se realicen. Objetivo: Determinar el valor diagnóstico de la electroforesis de proteínas y de las cadenas ligeras libres en suero en el mieloma múltiple. Metodología: Se realizó un estudio retrospectivo de los parámetros electroforesis de proteínas en suero y cadenas ligeras libres en suero a 43 pacientes con diagnóstico de mieloma múltiple por evaluación de la médula ósea. La electroforesis de proteínas se realizó por el método convencional de separación de proteínas sobre papel de acetato de celulosa y para las cadenas ligeras libres se aplicó un ensayo inmunoturbidimétrico en el que se usó un analizador químico (Cobas 311). Se calcularon 7 parámetros que evaluaron la exactitud diagnóstica. Resultados: Todos los parámetros que evaluaron la exactitud diagnóstica estuvieron dentro de los intervalos de confianza en ambas pruebas. Conclusiones: La electroforesis de proteínas y las cadenas ligeras libres en suero son ensayos de gran utilidad en el diagnóstico del mieloma múltiple y se deben utilizar en conjunto para la mayor captación posible de casos.
ABSTRACT Background: Protein electrophoresis and serum free light chains are techniques used in the diagnosis of multiple myeloma. However, the diagnostic utility of both tests may vary according to the method used and the actual conditions of the environment where they are performed. Objective: To determine the diagnostic value of protein electrophoresis and serum free light chains in multiple myeloma. Methodology: A retrospective study of serum protein electrophoresis parameters and serum free light chains was conducted in 43 patients diagnosed with multiple myeloma by bone marrow evaluation. Protein electrophoresis was completed by the conventional method of protein separation on cellulose acetate paper and for free light chains an immunoturbidimetric assay was applied in which a chemical analyzer (Cobas 311) was used. Seven parameters were calculated to evaluate diagnostic accuracy. Results: All parameters assessing diagnostic accuracy were within confidence intervals in both tests. Conclusions: Protein electrophoresis and serum free light chains are very useful assays in the diagnosis of multiple myeloma and should be used in conjunction for the highest possible approval of cases.
Subject(s)
Blood Protein Electrophoresis , Immunoglobulin kappa-Chains , Electrophoresis, Cellulose Acetate , Data Accuracy , Multiple Myeloma/diagnosisABSTRACT
Purpose: To compare the efficacy of topical nonsteroidal anti?inflammatory drugs (NSAIDs) and prednisolone acetate in controlling inflammation and preventing cystoid macular edema (CME) after uneventful phacoemulsification. Methods: All patients who underwent uneventful phacoemulsification from December 2020 to Feb 2021 were included in the study. These were randomly assigned to receive any one anti?inflammatory agent among topical nepafenac (0.1%) [96 eyes], bromfenac (0.07%) [93 eyes], preservative?free ketorolac (0.4%) [94 eyes], nepafenac (0.3%) [96 eyes], or prednisolone acetate (1%) [91 eyes]. The efficacy of the drugs was evaluated by comparing the grade of anterior chamber (AC) cells, conjunctival hyperemia, pain score, visual acuity, intraocular pressure (IOP), and central macular thickness (CMT) at 1 and 6 weeks after surgery. Results: At 1 and 6 weeks, there was no significant difference in pain score, conjunctival hyperemia, AC cells, change in IOP, and visual acuity between the prednisolone and the NSAIDs groups, though nepafenac 0.3% was most effective. At 6 weeks, there was no significant difference in the number of patients developing subclinical CME in the prednisolone versus NSAID group. The mean increase in CMT was significantly lower in nepafenac 0.3% than prednisolone at 1 and 6 weeks (P = 0.003 and 0.004, respectively). Conclusion: NSAIDs used in isolation are comparable to prednisolone in preventing inflammation and pain after uneventful phacoemulsification. However, nepafenac 0.3% is most comparable to prednisolone and more efficacious in reducing the incidence of CME. We recommend that nepafenac 0.3% can be used as a sole anti?inflammatory agent in patients with uneventful phacoemulsification.
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Objective@#The antibacterial properties and bonding strength of 3M orthodontic adhesive resin modified by chlorhexidine acetate (CHA) composite mesoporous silica were investigated.@*Methods@# CHA with different mass fractions was encapsulated in mesoporous silica nanoparticles (MSNs) (denoted CHA@MSNs). Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were used to characterize the samples. The 3M Z350XT flow resin was divided into 4 groups: group A: 3M+CHA@MSNs (0%); group B: 3M+CHA@MSNs (3%); group C: 3M+CHA@MSNs (5%); and group D: 3M+CHA@MSNs (6.4%), with mass scores of 0%, 3%, 5%, and 6.4%, respectively. The shear strength of the modified adhesive was tested by a universal electronic material testing machine, the adhesive residue was observed by a 10 × magnifying glass, and the adhesive Remnant index (ARI) was calculated. The four groups of modified adhesives were cultured with Streptococcus mutans. The OD540 value of the bacterial solution was measured by a spectrophotometer, and the amount of plaque attachment was observed by scanning electron microscopy to evaluate the antibacterial performance of the adhesives.@*Results@#Infrared spectroscopic analysis of CHA@MSNs showed that CHA was successfully loaded onto MSNs. Under scanning electron microscopy, it could be seen that, after Cha was combined with MSNs, the structure of MSNs changed, as the boundary was fuzzy and aggregated into a layered structure. A comparison of shear strength revealed a statistically significant difference between the groups containing CHA@MSNs and the groups without CHA@MSNs (P<0.05). The value of the shear strength in group D decreased the most, while there was no statistically significant difference between group B and group C (P > 0.05). There was no statistical significance across all groups (P > 0.05), suggesting that the addition of CHA@MSNs had little effect on the bracket shedding. The OD540 value of bacterial fluid indicated that the difference among groups A, B and C was statistically significant (P < 0.05), and the antibacterial effect of group C was the best; there was no statistically significant difference between group C and group D (P > 0.05).@*Conclusions@#Therefore, adding 5% CHA@MSN antibacterial agent significantly improved the antibacterial effect and did not affect the bond strength.