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1.
West Afr J Med ; 41(2): 175-182, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38581696

RESUMO

BACKGROUND: Maternal infections remain a significant contributor to maternal mortality worldwide. Majority of births in northern Nigeria occur at home and are attended by Traditional Birth Attendants (TBAs). Little has been documented about their knowledge and practice on infection prevention and control practices in Kano, northern Nigeria. OBJECTIVES: This study evaluated the level as well as factors associated with TBAs' infection prevention and control knowledge and practices. METHODS: The study is the baseline phase of a quasi-experimental study, conducted in a rural LGA in Kano State, Nigeria. Using an adapted tool, 163 eligible TBAs were surveyed. Knowledge and practice of IPC were scored, aggregated, and dichotomized into good or poor. Binary logistic regression analysis was used to predict knowledge and practice of IPC. RESULTS: Majority (79.1%) of the TBAs exhibited poor IPC knowledge but many (78.5%) reported good practice. Good knowledge of IPC was predicted by the TBAs' age: a six-fold increased likelihood (AOR=6.25, 95% CI: 1.02- 38.53) and almost five-fold increased likelihood (AOR=4.75, 95% CI: 1.39- 16.24) for those in their second and fourth decades of life. TBAs who reported poor practice of IPC were 83% less likely (AOR=0.17, 95% CI: 0.03- 0.92) to have good knowledge of IPC. TBAs' practice was only linked to previous training (AOR=0.17, 95% CI: 0.04- 0.76). CONCLUSION: TBAs knowledge of IPC was low although reported practice was good. The need for tailored training interventions to enhance knowledge and skills for safe delivery care is paramount to improve maternal and neonatal outcomes.


CONTEXTE: Les infections maternelles restent une contribution significative à la mortalité maternelle dans le monde. La majorité des accouchements dans le nord du Nigeria ont lieu à domicile et sont assistés par des TBA. Peu de choses ont été documentées sur leurs connaissances et leurs pratiques en matière de prévention et de contrôle des infections à Kano, dans le nord du Nigeria. OBJECTIFS: Cette étude a évalué le niveau de connaissances et de pratiques des TBA en matière de prévention et de contrôle des infections, ainsi que les facteurs associés. MÉTHODES: L'étude est la phase de base d'une étude quasiexpérimentale, menée dans une LGA rurale de l'État de Kano, au Nigeria. En utilisant un outil adapté, 163 TBA éligibles ont été interrogés. Les connaissances et les pratiques en matière de PCI ont été évaluées, agrégées et dichotomisées en bonnes ou mauvaises. Une analyse de régression logistique binaire a été utilisée pour prédire les connaissances et les pratiques en matière de PCI. RÉSULTATS: La majorité (79,1 %) des TBA présentaient des connaissances médiocres en PCI, mais beaucoup (78,5 %) ont déclaré avoir de bonnes pratiques. De bonnes connaissances en PCI étaient prédites par l'âge des TBA : une probabilité multipliée par six (AOR=6,25, IC à 95 % : 1,02-38,53) et presque multipliée par cinq (AOR=4,75, IC à 95 % : 1,39-16,24) pour ceux dans leur deuxième et quatrième décennies de vie. Les TBA qui ont déclaré une mauvaise pratique de la PCI étaient 83 % moins susceptibles (AOR=0,17, IC à 95 % : 0,03-0,92) d'avoir de bonnes connaissances en PCI. La pratique des TBA était uniquement liée à une formation antérieure (AOR=0,17, IC à 95 % : 0,04­0,76). CONCLUSION: Les connaissances des TBA en matière de PCI étaient faibles bien que les pratiques déclarées étaient bonnes. La nécessité d'interventions de formation sur mesure pour améliorer les connaissances et les compétences en matière de soins de l'accouchement sécurisés est primordiale pour améliorer les résultats maternels et néonatals. MOTS-CLÉS: Accoucheuses Traditionnelles, Mortalité Maternelle, Infection Maternelle, Nigeria.


Assuntos
Tocologia , Gravidez , Recém-Nascido , Humanos , Feminino , Tocologia/educação , Nigéria/epidemiologia , População Rural , Conhecimentos, Atitudes e Prática em Saúde , Mortalidade Materna
2.
Sci Rep ; 14(1): 565, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177275

RESUMO

To combat infections, silver was used extensively in biomedical field but there was a need for a capping agent to eliminate its cytotoxic effects. In this study, polymeric calcium polyphosphate was doped by silver with three concentrations 1, 3 or 5 mol.% and were characterized by TEM, XRD, FTIR, TGA. Moreover, cytotoxicity, antibacterial, cell migration and DNA fragmentation assays were done to assure its safety. The results showed that the increase in silver percentage caused an increase in particle size. XRD showed the silver peaks, which indicated that it is present in its metallic form. The TGA showed that thermal stability was increased by increasing silver content. The antibacterial tests showed that the prepared nanoparticles have an antibacterial activity against tested pathogens. In addition, the cytotoxicity results showed that the samples exhibited non-cytotoxic behavior even with the highest doping concentration (5% Ag-CaPp). The cell migration assay showed that the increase in the silver concentration enhances cell migration up to 3% Ag-CaPp. The DNA fragmentation test revealed that all the prepared nanoparticles caused no fragmentation. From the results we can deduce that 3% Ag-CaPp was the optimum silver doped calcium polyphosphate concentration that could be used safely for medical applications.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Prata/farmacologia , Cálcio , Fragmentação do DNA , Extratos Vegetais , Antibacterianos/farmacologia , Cálcio da Dieta , Movimento Celular , Testes de Sensibilidade Microbiana
3.
Genes (Basel) ; 14(10)2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37895271

RESUMO

Reduced feed intake during heat stress (HS) disrupts glucose homeostasis, thereby resulting in endoplasmic reticulum (ER) stress and triggering apoptosis in chickens. We hypothesize that glucose supplementation could reduce apoptosis in chickens raised under HS. This study comprised 456 28-day-old broiler chickens randomly assigned to four treatment combinations under glucose supplementation and HS. The treatments were TN0, TN6, HS0, and HS6 with two glucose levels (0% and 6%) and two temperature levels (25 °C (thermoneutral-TN) and 35 °C (8.00 AM to 8.00 PM, (HS)). After 7 days post-HS, the blood glucose level for the HS6 group was higher than for TN0, TN6, and HS0. We studied the mRNA expression of genes and caspase-3 activity in the four experimental groups. The expressions of GCN2, ATF4, CHOP, and FOXO3a increased during HS regardless of glucose supplementation, while PERK and MAFbx increased only under HS with glucose supplementation. We show that under TN conditions, glucose supplementation led to a significant increase in cellular apoptosis in the Pectoralis (P.) major. However, under HS with glucose, the level of apoptosis was similar to that of chickens raised under TN conditions with no glucose supplementation. The utility of glucose to curtail apoptosis under HS should be tested under other intense models of HS.


Assuntos
Galinhas , Glucose , Animais , Galinhas/genética , Glucose/farmacologia , Músculos Peitorais , Temperatura Alta , Suplementos Nutricionais , Resposta ao Choque Térmico/genética , Apoptose
4.
Cureus ; 15(7): e42061, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37601996

RESUMO

Background Multiple sclerosis (MS) is a chronic autoimmune disease caused by multiple factors. It can lead to many physical and mental symptoms. Fatigue is one of the most commonly mentioned complaints among MS patients that can affect their quality of life. Physical activity has many benefits for the physical and mental health of patients with MS. Aim To assess the role of exercise on fatigue among patients with multiple sclerosis and identify the relationship between depression, sleep quality, sociodemographic variables, and fatigue. Methods This is an analytical cross-sectional study based on a sample size of 235 patients recruited from the MS clinic at King Fahad Hospital (KFH) in Madinah. The outcome of the study was fatigue among MS patients. Data were collected through telephone calls from February to May 2022 using a structured questionnaire and scales, such as the Godin Leisure-Time Exercise Questionnaire (GLTEQ), Modified Fatigue Impact Scale (MFIS), Patient Health Questionnaire (PHQ2), and Pittsburgh Sleep Quality Index (PSQI). Data were analyzed through SPSS version 20 (IBM Corp., Armonk, NY, USA). The correlation coefficient (r), Chi-square tests, and simple and multiple logistic regression were used as found appropriate. Results Out of the total samples, 37.4% were male and 62.6% were female. The median age of patients was 36 years. The prevalence of fatigue was 37% among patients, with a reported median fatigue score of 26. It was found that 63% of the patients were physically inactive; 32.2% were overweight, 14.2% were obese; 63.8% of patients had poor sleep quality. The fatigue score was negatively correlated with the GLTEQ score, but the results were not significant (r=-0.066; P-value (level of significance)=0.335). Nonetheless, a moderately significant correlation was observed between the MFIS and PSQI and MFIS and PHQ2 (r=0.505, P=<0.001 and r=0.520, P=<0.001, respectively). The Chi-square test showed a significant association between fatigue and progressive types of MS, the primary progressive MS (PPMS), secondary progressive MS (SPMS), and relapsing-remitting MS (RRMS) (odds ratio (OR)=4.4; 95% confidence interval (CI): 2.1-8.9), P=<0.001). Depressed patients were 9.7 times more likely to develop fatigue compared to non-depressed patients (P=<0.001). Those with poor sleep quality were 4.6 times more likely to develop fatigue compared to those with good sleep quality (P=<0.001). Fifty-six percent of fatigue among MS patients were predicted by low income, progressive types, unemployment, obesity, depression, and poor sleep quality. Conclusion Fatigue is a major complaint among MS patients. Most of the patients were found to be physically inactive, depressed, and have poor sleep quality. This study found an association between physical inactivity and fatigue, but the results were not significant. There was a significant association between sociodemographic factors like low income and unemployment, poor sleep quality, obesity, progressive types of MS, depression, and fatigue. Encouraging exercise practice and implementing a regular exercise program are needed, along with weight management plans. Further studies and psychological support meetings are required, with the importance of a holistic approach to patient care.

5.
Nutrients ; 15(12)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37375613

RESUMO

Pomegranate juice concentrate (PJC) is a rich source of polyphenols, which exhibit significant antioxidant activity and potential health benefits for disease prevention and therapy. In this study, the polyphenolic profile of PJC was investigated for the first time, and it was found that PJC can inhibit oxidative damage to bovine serum albumin (BSA) and deoxyribonucleic acid (DNA), as well as acetylcholinesterase, α-amylase, and tyrosinase activities. The primary polyphenols identified in PJC were 4-Hydroxy-3-Methoxybenzoate, epicatechin, catechin, rutin, ferulic acid, P-coumaric acid, and cinnamic acid. Additionally, PJC demonstrated potent antibacterial effects against human pathogens such as Streptococcus mutans and Aeromonas hydrophila and dose-dependently reduced the proliferation of colorectal, breast, and hepatic cancer cells via apoptosis. Furthermore, PJC blocked B-cell lymphoma 2 (BCl-2) and the expression of a potent cyclin-dependent kinase inhibitor (P21) and enhanced tumor protein (P53) expression, compared to both untreated cells and cells treated with fluoropyrimidine 5-fluorouracil (5-FU). As a result, PJC may be a beneficial ingredient in the formulation of emerging natural-compound-based chemotherapy and functional foods and could be utilized by the food, nutraceutical, and pharmaceutical industries.


Assuntos
Anti-Infecciosos , Punica granatum , Humanos , Antioxidantes/farmacologia , Acetilcolinesterase , Polifenóis/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios
6.
Nutrients ; 15(11)2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37299576

RESUMO

Palm fruit pollen extract (PFPE) is a natural source of bioactive polyphenols. The primary aim of the study was to determine the antioxidant, antimicrobial, anticancer, enzyme inhibition, bovine serum albumin (BSA), and DNA-protective properties of PFPE and identify and quantify the phenolic compounds present in PFPE. The results demonstrated that PFPE exhibited potent antioxidant activity in various radical-scavenging assays, including (2,2-diphenyl-1-picrylhydrazyl) (DPPH•), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•), nitric oxide (NO), ferric-reducing/antioxidant power (FRAP), and total antioxidant capacity (TAC). PFPE also displayed antimicrobial activity against several pathogenic bacteria. Similarly, PFPE reduced acetylcholinesterase, tyrosinase, and α-amylase activities. PFPE has been proven to have an anticancer effect against colon carcinoma (Caco-2), hepatoma (HepG-2), and breast carcinoma (MDA) cancer cells. Apoptosis occurred in PFPE-treated cells in a dose-dependent manner, and cell cycle arrest was observed. Furthermore, in breast cancer cells, PFPE down-regulated Bcl-2 and p21 and up-regulated p53 and Caspase-9. These results show that PFPE constitutes a potential source of polyphenols for pharmaceutical, nutraceutical, and functional food applications.


Assuntos
Neoplasias , Phoeniceae , Humanos , Antioxidantes/farmacologia , Frutas/química , Acetilcolinesterase , Células CACO-2 , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Polifenóis/análise , DNA , Neoplasias/tratamento farmacológico
7.
Antimicrob Agents Chemother ; 67(7): e0027723, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37166191

RESUMO

Resistant Gram-negative bacteria are a growing concern in the United States, leading to significant morbidity and mortality. We identified a 72-year-old female patient who presented with unilateral vision loss. She was found to have a large corneal ulcer with hypopyon. Culture of corneal scrapings grew extensively drug-resistant Pseudomonas aeruginosa. Treatment involved a combination of systemic and topical antibiotics. Whole genome sequencing revealed the presence of blaVIM-80, blaGES-9, and other resistance determinants. This distinctive organism was linked to an over-the-counter artificial tears product.


Assuntos
Úlcera da Córnea , Infecções por Pseudomonas , Feminino , Humanos , Idoso , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Pseudomonas aeruginosa/genética , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas , Infecções por Pseudomonas/microbiologia , Testes de Sensibilidade Microbiana
8.
Pharmaceuticals (Basel) ; 16(3)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36986552

RESUMO

Irreversible myocardial injury causes the exhaustion of cellular adenosine triphosphate (ATP) contributing to heart failure (HF). Cyclocreatine phosphate (CCrP) was shown to preserve myocardial ATP during ischemia and maintain cardiac function in various animal models of ischemia/reperfusion. We tested whether CCrP administered prophylactically/therapeutically prevents HF secondary to ischemic injury in an isoproterenol (ISO) rat model. Thirty-nine rats were allocated into five groups: control/saline, control/CCrP, ISO/saline (85 and 170 mg/kg/day s.c. for 2 consecutive days), and ISO/CCrP (0.8 g/kg/day i.p.) either administrated 24 h or 1 h before ISO administration (prophylactic regimen) or 1 h after the last ISO injection (therapeutic regimen) and then daily for 2 weeks. CCrP protected against ISO-induced CK-MB elevation and ECG/ST changes when administered prophylactically or therapeutically. CCrP administered prophylactically decreased heart weight, hs-TnI, TNF-α, TGF-ß, and caspase-3, as well as increased EF%, eNOS, and connexin-43, and maintained physical activity. Histology indicated a marked decrease in cardiac remodeling (fibrin and collagen deposition) in the ISO/CCrP rats. Similarly, therapeutically administered CCrP showed normal EF% and physical activity, as well as normal serum levels of hs-TnI and BNP. In conclusion, the bioenergetic/anti-inflammatory CCrP is a promising safe drug against myocardial ischemic sequelae, including HF, promoting its clinical application to salvage poorly functioning hearts.

9.
Cureus ; 15(2): e35060, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36942189

RESUMO

Accidental foreign body (FB) ingestion is common in the elderly, particularly edentulous and denture wearers. The most commonly ingested FBs are food-related, including fish and chicken bones. While small FBs can pass through the gastrointestinal tract without any complications, large or irregular-shaped FBs usually cause complications. These complications include choking, ulceration, perforation, fistula, abscess formation, or even death. Ingestion of a large chicken bone that reaches the anal canal without causing injury is extremely rare. We present a rare case of accidental chicken bone (xiphoid process) ingestion that manifested itself by projecting from the anus while defecating. Interestingly, the patient did not experience any food choking or abdominal pain, nor did she have any type of dementia. However, the patient could not grind food properly due to the loss of her upper molar teeth, which made her develop a habit of rapid swallowing. On examination, the chicken bone was seen within the anus with a sharp edge embedded in the mucosal wall. While a plain pelvic X-ray failed to display the FB, a pelvic CT scan with a 3D illustration showed its dimensions (5.0 x 2.5 x 3 cm). A plain pelvic CT scan confirmed the presence of the bone-contrast FB within the anal canal without injuring the surrounding anatomical structures. The FB was gently manipulated and successfully extracted after administering 5 ml of lidocaine gel enema. The patient was counseled regarding proper chewing habits, and she was referred to a dental clinic for a professional assessment. Seven days later, the patient was seen again at the clinic for a follow-up and was found to have an uneventful recovery. Maintaining good dental health and proper eating habits, as well as increasing awareness among edentulous individuals and denture wearers, are required to prevent accidental FB ingestions.

10.
Chem Biodivers ; 20(2): e202200918, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36602020

RESUMO

In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different parts of E. mauritanica were in vitro screened for anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC/MS/MS, molecular networking and NMR, the chemical profile of the active extract was determined. To determine the optimum target for these compounds, docking experiments of the active extract's identified compounds were conducted at several viral targets. The leaves extract showed the best inhibitory effect with IC50 8.231±0.04 µg/ml. The jatrophane diterpenes were provisionally annotated as the primary metabolites of the bioactive leaves extract based on multiplex of LC/MS/MS, molecular network, and NMR. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro, where compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects on SARS-Cov-2 and its molecular targets.


Assuntos
COVID-19 , Diterpenos , Euphorbia , Estrutura Molecular , Euphorbia/química , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , SARS-CoV-2 , Diterpenos/química , Extratos Vegetais/química
11.
Comb Chem High Throughput Screen ; 26(12): 2124-2148, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36650620

RESUMO

Toll-like receptors (TLRs) control both innate and adaptive immunity with a wide expression on renal epithelial cells and leukocytes. Activation of TLRs results in the production of cytokines, chemokines and interferons along with activation of the transcription factor NF-κB, resulting in inflammatory perturbations. TLR4 signaling pathway is the most extensively studied of TLRs. TLR4 is expressed on renal microvascular endothelial and tubular epithelial cells. So, targeting TLR4 modulation could be a therapeutic approach to attenuate kidney diseases that are underlined by inflammatory cascade. Medicinal plants with anti-inflammatory activities display valuable effects and are employed as alternative sources to alleviate renal disease linked with inflammation. Flavonoids and other phytochemicals derived from traditional medicines possess promising pharmacological activities owing to their relatively cheap and high safety profile. Our review focuses on the potent anti-inflammatory activities of twenty phytochemicals to verify if their potential promising renoprotective effects are related to suppression of TLR4 signaling in different renal diseases, including sepsis-induced acute kidney injury, renal fibrosis, chemotherapy-induced nephrotoxicity, diabetic nephropathy and renal ischemia/reperfusion injury. Additionally, molecular docking simulations were employed to explore the potential binding affinity of these phytochemicals to TLR4 as a strategy to attenuate renal diseases associated with activated TLR4 signaling.


Assuntos
Nefropatias Diabéticas , Receptor 4 Toll-Like , Humanos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/uso terapêutico , Simulação de Acoplamento Molecular , Rim/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
12.
Plants (Basel) ; 11(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36365342

RESUMO

Acacia nilotica (synonym: Vachellia nilotica (L.) P.J.H.Hurter and Mabb.) is considered an important plant of the family Fabaceae that is used in traditional medicine in many countries all over the world. In this work, the antiviral potentialities of the chemically characterized essential oils (EOs) obtained from the bark and fruits of A. nilotica were assessed in vitro against HAV, HSV1, and HSV2. Additionally, the in silico evaluation of the main compounds in both EOs was carried out against the two proteins, 3C protease of HAV and thymidine kinase (TK) of HSV. The chemical profiling of the bark EOs revealed the identification of 32 compounds with an abundance of di- (54.60%) and sesquiterpenes (39.81%). Stachene (48.34%), caryophyllene oxide (19.11%), and spathulenol (4.74%) represented the main identified constituents of bark EO. However, 26 components from fruit EO were assigned, with the majority of mono- (63.32%) and sesquiterpenes (34.91%), where trans-caryophyllene (36.95%), Z-anethole (22.87%), and γ-terpinene (7.35%) represented the majors. The maximum non-toxic concentration (MNTC) of the bark and fruits EOs was found at 500 and 1000 µg/mL, respectively. Using the MTT assay, the bark EO exhibited moderate antiviral activity with effects of 47.26% and 35.98% and a selectivity index (SI) of 2.3 and 1.6 against HAV and HSV1, respectively. However, weak activity was observed via the fruits EO with respective SI values of 3.8, 5.7, and 1.6 against HAV, HSV1, and HSV2. The in silico results exhibited that caryophyllene oxide and spathulenol (the main bark EO constituents) showed the best affinities (ΔG = -5.62, -5.33, -6.90, and -6.76 kcal/mol) for 3C protease and TK, respectively. While caryophyllene (the major fruit EO component) revealed promising binding capabilities against both proteins (ΔG = -5.31, -6.58 kcal/mol, respectively). The molecular dynamics simulation results revealed that caryophyllene oxide has the most positive van der Waals energy interaction with 3C protease and TK with significant binding free energies. Although these findings supported the antiviral potentialities of the EOs, especially bark EO, the in vivo assessment should be tested in the intraoral examination for these EOs and/or their main constituents.

13.
Nutrients ; 14(14)2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35889814

RESUMO

Bee pollen is a natural cocktail of floral nectar, flower pollen, enzymes, and salivary secretions produced by honeybees. Bee pollen is one of the bee products most enriched in proteins, polysaccharides, polyphenols, lipids, minerals, and vitamins. It has a significant health and medicinal impact and provides protection against many diseases, including diabetes, cancer, infectious, and cardiovascular. Bee pollen is commonly promoted as a cost-effective functional food. In particular, bee pollen has been applied in clinical trials for allergies and prostate illnesses, with a few investigations on cancer and skin problems. However, it is involved in several patents and health recipes to combat chronic health problems. This review aimed to highlight the clinical trials and patents involving bee pollen for different cases and to present the role of bee pollen as a supplementary food and a potential product in cosmetic applications.


Assuntos
Néctar de Plantas , Pólen , Animais , Abelhas , Masculino , Minerais/metabolismo , Néctar de Plantas/metabolismo , Pólen/química , Polifenóis/metabolismo , Vitaminas/análise
14.
Biomed Chromatogr ; 36(9): e5427, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35708053

RESUMO

The use of complementary medicine (CMD) for liver support in Hepatitis C virus (HCV) patients sometimes coincides with the administration of oral antiviral drugs to eradicate the virus. This calls for a deep investigation of CMD effects on the pharmacokinetic parameters of these drugs to ensure their safety and efficacy. Silymarin (SLY), as a CMD, was selected to be given orally to healthy male rats with sofosbuvir (SFB) and ledipasvir (LED), a common regimen in HCV treatment. A new and sensitive LC-MS method was validated for the bioassay of SLY, LED, SFB and its inactive metabolite, GS-331007, in spiked plasma with lower limits of quantitation of 10, 1, 4 and 10 ng/ml, respectively. Moreover, the method was further applied to conduct a full pharmacokinetic profile of SFB, GS-331007 and ledipasvir with and without SLY. It was found that co-administration of SLY may expose the patient to unplanned high serum concentrations of SFB and LED. This could be accompanied by a decrease in SFB efficacy, potentially leading to therapeutic failure and the emergence of viral resistance.


Assuntos
Hepatite C , Silimarina , Animais , Antivirais/farmacocinética , Benzimidazóis , Cromatografia Líquida , Quimioterapia Combinada , Fluorenos , Hepacivirus , Hepatite C/tratamento farmacológico , Masculino , Ratos , Silimarina/farmacologia , Sofosbuvir , Espectrometria de Massas em Tandem
15.
PLoS One ; 17(6): e0269131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35657942

RESUMO

Eimeria (E.) maxima is one of the most pathogenic Eimeria spp persistently invading the middle jejunum and ileum, damaging the intestinal mucosa of chickens. Heat stress (HS) is a common stressor and equally contributes to inflammation and oxidative stress. We investigated the effect of E. maxima infection and HS on ileal digestibility, mRNA expression of nutrient transporters, and ileal tissue morphology in broiler chickens. There were four treatment groups: thermoneutral control (TNc), thermoneutral infected (TNi), heat stress control (HSc), and heat stress infected (HSi), 6 replicates each of 10 birds per treatment. Chickens were fed a diet containing 0.2% TiO2. At 6-day-post infection, ileal content and tissue were collected to quantify ileal digestibility of crude protein and fat, mRNA levels of nutrient transporters and histopathology. Growth and feed intake were reduced in all treatment groups, compared with the TNc. Contrary to expectation, the combination of two major stressors (E. maxima and HS) in the TNi group exhibited almost normal digestibility while only the TNi birds expressed severe digestibility depression, compared with the TNc group. The TNi group showed the lowest mRNA expression of the transporters: SGLT1, GLUT2-5-8-10-12, FABP1-2-6, and PEPT1 compared with the other treatment groups. The expression of the absorptive enterocytes' gene markers (ACSL5, IAP, and SGLT1) supported by the ileal tissue morphology indicated that the TNi group had the highest enterocytic destruction. The expression of oxidative genes (iNOS and CYBB) dramatically increased only in the TNi group compared with the other treatment groups. Our results showed that exposing broiler chickens to HS can mitigate the disruptive effect of E. maxima on the ileal digestibility and absorption by limiting the parasite-induced tissue injury and suppressing the enterocytic inducible oxidative damage.


Assuntos
Eimeria , Transtornos de Estresse por Calor , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/genética , Dieta/veterinária , Suplementos Nutricionais , Digestão , Eimeria/genética , Transtornos de Estresse por Calor/metabolismo , Resposta ao Choque Térmico , Íleo/metabolismo , Carne , Nutrientes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
Abdom Radiol (NY) ; 47(7): 2494-2499, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35583821

RESUMO

PURPOSE: To investigate whether use of an enema prep reduces the false-negative (FN) rate of PI-RADS 1 MRI of the prostate for clinically significant prostate cancer (csPCa). MATERIALS AND METHODS: 1108 consecutive patients with a PI-RADS 1 MRI performed 01/2016-09/2021 were retrospectively collected. Patient charts were examined for subsequent systematic prostate biopsy performed within 1 year if positive or anytime thereafter if negative. Patients without biopsy were excluded. Use of an enema prep 1-2 h before MRI, which was implemented in 03/2019, was recorded. FN rate of MRI for detection of csPCa, defined as Gleason score ≥ 7, using systematic biopsy was assessed per patient and compared between those with and without an enema prep. Χ2 test and logistic regression were performed. RESULTS: 255 patients (median age 64, IQR 58-69) with median PSA 5.6 (IQR 4.2-8.1), PI-RADS 1 MRI, and subsequent biopsy were included in the analysis. 66 patients (26%) had an enema prep and 189 patients (74%) did not. 7 (11%) patients with and 21 (11%) patients without enema prep had a FN biopsy. There was no significant association between enema prep and FN biopsy (OR 0.95, 95% CI 0.38-2.35, p = 0.91). CONCLUSIONS: Use of an enema prep prior to prostate MRI did not decrease the FN rate of PI-RADS 1 MRI of the prostate for clinically significant prostate cancer.


Assuntos
Próstata , Neoplasias da Próstata , Enema , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos Retrospectivos
17.
PLoS One ; 17(3): e0264969, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35286313

RESUMO

α-glucosidase inhibitors represent an important class of type 2 antidiabetic drugs and they act by lowering postprandial hyperglycemia. Today, only three synthetic inhibitors exist on the market, and there is a need for novel, natural and more efficient molecules exhibiting this activity. In this study, we investigated the ability of Tamarix nilotica ethanolic and aqueous shoot extracts, as well as methanolic fractions prepared from aqueous crude extracts to inhibit α-glucosidase. Both, 50% ethanol and aqueous extracts inhibited α-glucosidase in a concentration-dependent manner, with IC50 values of 12.5 µg/mL and 24.8 µg/mL, respectively. Importantly, α-glucosidase inhibitory activity observed in the T. nilotica crude extracts was considerably higher than pure acarbose (IC50 = 151.1 µg/mL), the most highly prescribed α-glucosidase inhibitor on the market. When T. nilotica crude extracts were fractionated using methanol, enhanced α-glucosidase inhibitory activity was observed in general, with the highest observed α-glucosidase inhibitory activity in the 30% methanol fraction (IC50 = 5.21 µg/mL). Kinetic studies further revealed a competitive reversible mechanism of inhibition by the plant extract. The phytochemical profiles of 50% ethanol extracts, aqueous extracts, and the methanolic fractions were investigated and compared using a metabolomics approach. Statistical analysis revealed significant differences in the contents of the crude extracts and fractions and potentially identified the molecules that were most responsible for these observed variations. Higher α-glucosidase inhibitory activity was associated with an enrichment of terpenoids, fatty acids, and flavonoids. Among the identified molecules, active compounds with known α-glucosidase inhibitory activity were detected, including unsaturated fatty acids, triterpenoids, and flavonoid glycosides. These results put forward T. nilotica as a therapeutic plant for type 2 diabetes and a source of α-glucosidase inhibitors.


Assuntos
Diabetes Mellitus Tipo 2 , Tamaricaceae , Etanol , Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Cinética , Metanol , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Tamaricaceae/metabolismo , alfa-Glucosidases/metabolismo
18.
Exp Neurol ; 351: 113987, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35065054

RESUMO

Traumatic brain injury (TBI) is a major cause of disability and death. Mild TBI (mTBI) constitutes ~75% of all TBI cases. Repeated exposure to mTBI (rmTBI), leads to the exacerbation of the symptoms compared to single mTBI. To date, there is no FDA-approved drug for TBI or rmTBI. This research aims to investigate possible rmTBI neurotherapy by targeting TBI pathology-related mechanisms. Oxidative stress is partly responsible for TBI/rmTBI neuropathologic outcomes. Thus, targeting oxidative stress may ameliorate TBI/rmTBI consequences. In this study, we hypothesized that mitoquinone (MitoQ), a mitochondria-targeted antioxidant, would ameliorate TBI/rmTBI associated pathologic features by mitigating rmTBI-induced oxidative stress. To model rmTBI, C57BL/6 mice were subjected to three concussive head injuries. MitoQ (5 mg/kg) was administered intraperitoneally to rmTBI+MitoQ mice twice per week over one month. Behavioral and cognitive outcomes were assessed, 30 days following the first head injury, using a battery of behavioral tests. Immunofluorescence was used to assess neuroinflammation and neuronal integrity. Also, qRT-PCR was used to evaluate the expression levels of antioxidant enzymes. Our findings indicated that MitoQ alleviated fine motor function and learning impairments caused by rmTBI. Mechanistically, MitoQ reduced astrocytosis, microgliosis, dendritic and axonal shearing, and increased the expression of antioxidant enzymes. MitoQ administration following rmTBI may represent an efficient approach to ameliorate rmTBI neurological and cellular outcomes with no observable side effects.


Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Concussão Encefálica/complicações , Concussão Encefálica/tratamento farmacológico , Concussão Encefálica/patologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Suplementos Nutricionais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Compostos Organofosforados , Estresse Oxidativo , Ubiquinona/análogos & derivados
19.
JCO Oncol Pract ; 18(4): e574-e585, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34905410

RESUMO

PURPOSE: Emergency department observation units (EDOUs) have been shown to decrease length of stay and improve cost effectiveness. Yet, compared with noncancer patients, patients with cancer are placed in EDOUs less often. In this study, we aimed to describe patients who were placed in a cancer center's EDOU to discern their clinical characteristics and outcomes. METHODS: We performed a retrospective observational study that included all patients age 18 years and older who presented to our emergency department (ED) and were placed in the EDOU between March 1, 2019, and February 29, 2020. The patients' electronic medical records were queried for demographics, comorbidities, diagnosis at the time of placement in the EDOU, length of stay, disposition from the EDOU, ED return within 72 hours after discharge from the EDOU, and mortality outcomes at 14 and 30 days. RESULTS: A total of 2,461 visits were eligible for analysis. Cancer-related pain was the main reason for observation in more than one quarter of the visits. The median length of stay in the EDOU was approximately 23 hours, and 69.6% of the patients were discharged. The ED return rate for unscheduled visits at 72 hours was 1.9%. The 14- and 30-day mortality rates were significantly higher for patients who were admitted than for those who were discharged (14 days: 1.7% v 0.3%, P < .001; 30 days: 5.9% v 1.8%, P < .001). CONCLUSION: Our data suggest that placing patients with cancer in EDOUs is safe, reduces admissions, and reserves hospital resources for patients who can receive the most benefit without compromising care.


Assuntos
Unidades de Observação Clínica , Neoplasias , Adolescente , Serviço Hospitalar de Emergência , Hospitalização , Humanos , Tempo de Internação , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia , Estudos Retrospectivos
20.
J Am Heart Assoc ; 10(24): e023227, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34873915

RESUMO

Background The complexity of the interaction between metabolic dysfunction and cardiovascular complications has long been recognized to extend beyond simple perturbations of blood glucose levels. Yet, structured interventions targeting the root pathologies are not forthcoming. Growing evidence implicates the inflammatory changes occurring in perivascular adipose tissue (PVAT) as early instigators of cardiovascular deterioration. Methods and Results We used a nonobese prediabetic rat model with localized PVAT inflammation induced by hypercaloric diet feeding, which dilutes inorganic phosphorus (Pi) to energy ratio by 50%, to investigate whether Pi supplementation ameliorates the early metabolic impairment. A 12-week Pi supplementation at concentrations equivalent to and twice as much as that in the control diet was performed. The localized PVAT inflammation was reversed in a dose-dependent manner. The increased expression of UCP1 (uncoupling protein1), HIF-1α (hypoxia inducible factor-1α), and IL-1ß (interleukin-1ß), representing the hallmark of PVAT inflammation in this rat model, were reversed, with normalization of PVAT macrophage polarization. Pi supplementation restored the metabolic efficiency consistent with its putative role as an UCP1 inhibitor. Alongside, parasympathetic autonomic and cerebrovascular dysfunction function observed in the prediabetic model was reversed, together with the mitigation of multiple molecular and histological cardiovascular damage markers. Significantly, a Pi-deficient control diet neither induced PVAT inflammation nor cardiovascular dysfunction, whereas Pi reinstatement in the diet after a 10-week exposure to a hypercaloric low-Pi diet ameliorated the dysfunction. Conclusions Our present results propose Pi supplementation as a simple intervention to reverse PVAT inflammation and its early cardiovascular consequences, possibly through the interference with hypercaloric-induced increase in UCP1 expression/activity.


Assuntos
Tecido Adiposo , Suplementos Nutricionais , Inflamação , Fósforo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Inflamação/complicações , Inflamação/prevenção & controle , Doenças Metabólicas/prevenção & controle , Fósforo/uso terapêutico , Estado Pré-Diabético , Ratos
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