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1.
Toxics ; 12(6)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38922115

RESUMO

This study utilizes Mentha piperita (MI) for the first time to investigate the uptake and translocation of chlorpyrifos (CPF; 10 µg g-1) from soil, introducing a new approach to improve the efficacy of this technique, which includes using biosurfactants (Bacillus subtilis and Pseudomonas aeruginosa) at 107 CFU/mL to degrade CPF under greenhouse conditions. Moreover, antioxidant enzymes, including superoxide dismutase (SOD) and peroxidase (Prx), and oxidative stress due to hydrogen peroxide (H2O2) and malondialdehyde (MDA) in MI roots and leaves were evaluated under CPF stress. Our results demonstrated that amending soil with MI and B. subtilis followed by P. aeruginosa significantly reduced CPF levels in the soil (p > 0.05) and enhanced CPF concentrations in MI roots and leaves after 1, 3, 7, 10, and 14 days of the experiment. Furthermore, CPF showed its longest half-life (t1/2) in soil contaminated solely with CPF, lasting 15.36 days. Conversely, its shortest half-life occurred in soil contaminated with CPF and treated with MI along with B. subtilis, lasting 4.65 days. Soil contaminated with CPF and treated with MI and P. aeruginosa showed a half-life of 7.98 days. The half-life (t1/2) of CPF-contaminated soil with MI alone was 11.41 days. A batch equilibrium technique showed that B. subtilis is better than P. aeruginosa for eliminating CPF from soil in In vitro experiments. Notably, CPF-polluted soil treated with coadministration of MI and the tested bacteria improved the activities of SOD and Prx and reduced H2O2 and MDA compared with CPF-polluted soil treated with MI alone. Our findings demonstrated that using B. subtilis and P. aeruginosa as biosurfactants to augment phytoremediation represents a commendable strategy for enhancing the remediation of CPF contamination in affected sites while reducing the existence of harmful pesticide remnants in crop plants.

3.
Chem Biol Interact ; 393: 110957, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38513929

RESUMO

Huntington's disease (HD) is an inheritable autosomal-dominant disorder that targets mainly the striatum. 3-Nitropropionic acid (3-NP) induces obvious deleterious behavioral, neurochemical, and histological effects similar to the symptoms of HD. Our study aimed to examine the neuroprotective activity of tropisetron, an alpha-7 neuronal nicotinic acetylcholine receptor (α-7nAChR) agonist, against neurotoxic events associated with 3-NP-induced HD in rats. Forty-eight rats were randomly allocated into four groups. Group I received normal saline, while Groups II, III and IV received 3-NP for 2 weeks. In addition, Group III and IV were treated with tropisetron 1 h after 3-NP administration. Meanwhile, Group IV received methyllycaconitine (MLA), an α-7nAChR antagonist, 30 min before tropisetron administration. Treatment with tropisetron improved motor deficits as confirmed by the behavioral tests and restored normal histopathological features of the striatum. Moreover, tropisetron showed an anti-oxidant activity via increasing the activities of SDH and HO-1 as well as Nrf2 expression along with reducing MDA level. Tropisetron also markedly upregulated the protein expression of p-PI3K and p-Akt which in turn hampered JAK2/NF-κB inflammatory cascade. In addition, tropisetron showed an anti-apoptotic activity through boosting the expression of Bcl-2 and reducing Bax expression and caspase-3 level. Interestingly, all the aforementioned effects of tropisetron were blocked by pre-administration of MLA, which confirms that such neuroprotective effects are mediated via activating of α-7nAChR. In conclusion, tropisetron showed a neuroprotective activity against 3-NP-induced HD via activating PI3K/Akt signaling and suppressing JAK2/NF-κB inflammatory axis. Thus, repositioning of tropisetron could represent a promising therapeutic strategy in management of HD.


Assuntos
Doença de Huntington , Fármacos Neuroprotetores , Receptores Nicotínicos , Animais , Ratos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Doença de Huntington/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , NF-kappa B/metabolismo , Nitrocompostos/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Propionatos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Nicotínicos/metabolismo , Transdução de Sinais , Tropizetrona/uso terapêutico
5.
Int Immunopharmacol ; 127: 111457, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38160566

RESUMO

Cisplatin is a highly effective antitumor agent, but its clinical use is limited due to critical adverse reactions including acute kidney injury (AKI). Nicorandil is an approved antianginal agent decreasing ischemia by potassium channel opening. The aim of this study was to investigate the nephroprotective effects of nicorandil and the possible role of activating PI3K/AKT/mTOR pathway in ameliorating cisplatin-induced AKI. Forty male Wistar rats were randomly allocated in 4 groups (n = 10). Group I: rats received the vehicle and served as control. Group II: rats received a single dose of cisplatin (7 mg/kg, i.p) on the 10th day of the experiment and served as AKI group. Group III: rats received cisplatin as in group II and nicorandil (3 mg/kg/day, p.o) for 14 days. Group IV: rats received cisplatin and nicorandil as in group III as well as wortmannin (15 µg/kg, i.v) for 14 days. Nicorandil exhibited obvious nephroprotective effects via the activation of PI3K/AKT/mTOR pathway. Moreover, nicorandil succeed to reduce the expression of the autophagy markers beclin-1 and LC-3II/I. In parallel, nicorandil showed anti-inflammatory and antiapoptotic effects via inhibition of NF-κB inflammatory pathway and depression of Bax/Bcl-2 ratio. Wortmannin, the PI3K inhibitor, was used to demonstrate the proposed pathway. Our study showed the nephroprotective effects of nicorandil in cisplatin-induced AKI in rats via activation of PI3K/AKT/mTOR signaling cascade, inhibition of autophagy, anti-inflammatory, anti-apoptotic, anti-oxidant activities. Thus, nicorandil could represent a promising renoprotective agent in cancer patients treated with cisplatin.


Assuntos
Injúria Renal Aguda , Cisplatino , Humanos , Ratos , Masculino , Animais , Cisplatino/efeitos adversos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Nicorandil/farmacologia , Nicorandil/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Wortmanina/farmacologia , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Apoptose
6.
BMC Urol ; 23(1): 117, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438810

RESUMO

BACKGROUND: Post-circumcision penile ischemia is a devastating complication. We will present our experience in managing children with various forms of penile ischemia. MATERIALS AND METHODS: This cohort prospective observational and interventional study was performed on all male children with post-circumcision penile ischemia between April 2017 and October 2021. A designed and approved protocol includes a combination of early pentoxifylline infusion, hyperbaric oxygen inhalation, early catheterization, and appropriate surgical debridement were applied for patients with deep ischemia 11/23, mainly the necrotic skin and subcutaneous tissues. Data of patient age, anesthesia method, monopolar diathermy usage, early presentation and positive wound culture were collected and analyzed statistically. RESULTS: During the study period 3,382 children were circumcised for non-medical reasons; 23 children were diagnosed with penile ischemia (0.7%), among other complications (9%). Most of the penile ischemia is associated with the use of monopolar diathermy (74%). The use of compressive wound dressing to control post-circumcision bleeding and infections is also responsible for ischemia in 52.2% and 43.5% of the cases. Inexperienced physicians were commonly responsible for ischemia (73.9%). Patients managed at first 24 h had better outcomes than those who were presented later (p = 0.001). CONCLUSION: In children with post-circumcision penile ischemia, a combination of hyperbaric oxygen therapy and pentoxifylline is especially effective for patients with skin and facial necrosis, this management reduces penile tissue loss.


Assuntos
Circuncisão Masculina , Oxigenoterapia Hiperbárica , Hipertermia Induzida , Pentoxifilina , Criança , Humanos , Masculino , Circuncisão Masculina/efeitos adversos , Pentoxifilina/uso terapêutico , Pênis
7.
J Gastrointest Surg ; 27(7): 1345-1352, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37020159

RESUMO

BACKGROUND: Sleeve gastrectomy (SG) continues to be one of the most popular bariatric procedures all over the world. Thyroid-stimulating hormone (TSH) frequently shows a slight elevation in patients with obesity. The effect of SG on thyroid hormones has been rarely investigated. AIM OF THE STUDY: This study aimed to assess the short-term effect of SG on thyroid functions in Egyptian patients with morbid obesity and the potential predictors of the postoperative thyroid functions. PATIENTS AND METHODS: This study included patients undergoing SG at kasr al ainy hospitals. The patients underwent preoperative 3-, 6-, and 12-month postoperative analyses of the thyroid functions and other biochemical markers. RESULTS: The study included 106 patients who showed significant improvement in thyroid functions at the follow-up assessment. Twelve-month TSH positively correlated with the 12-month measures of LDL and HbA1c. TSH change at 12-month follow-up (TSH) was inversely correlated to 12-month BMI and positively correlated to preoperative TSH and 12-month percentage of total weight loss (TWL%). Univariable linear regression analysis demonstrated that preoperative TSH (p < 0.001), 12-month TWL% (p = 0.042), 12-month HbA1c (p = 0.001), and 12-month LDL (p = 0.049) were significant predictors for the 12-month TSH levels. Multivariable analysis showed that only preoperative TSH levels (p < 0.001) and 12-month HbA1c levels (p = 0.021) could affect the 12-month TSH levels. CONCLUSION: The current study supports the evidence of thyroid function improvement after sleeve gastrectomy. This improvement was affected by the amount of weight loss after surgery.


Assuntos
Gastrectomia , Laparoscopia , Obesidade Mórbida , Tireotropina , Obesidade Mórbida/cirurgia , Laparoscopia/métodos , Gastrectomia/efeitos adversos , Testes de Função Tireóidea , Tireotropina/sangue , Humanos , Redução de Peso , Egito , Glândula Tireoide/fisiologia , Resultado do Tratamento , Estudos Retrospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
8.
Int J Urol ; 30(6): 526-531, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36872075

RESUMO

OBJECTIVE: To define and classify megameatus anomalies, the parameters of a considerable number of cases were investigated and compared with those of normal children. METHODS: A total of 1150 normal babies were examined during routine nonmedical circumcision, and another 750 boys referred with hypospadias were examined during the previous 3 years. All patients were evaluated and assessed for the size, location, and configuration of the urinary meatus, and penile length and girth were measured. Children with normal size and location of the meatus were considered control group A, and 42 cases of different forms of megameatus were considered group B. Other penoscrotal, urinary, and general anomalies were examined and investigated accordingly. All data were analyzed by the SPSS 9.0.1 statistical package and compared by paired t tests. RESULTS: Forty-two uncircumcised patients aged from 1 month to 4 years (mean 18 months) were diagnosed with a urinary meatus that engrossed the whole ventral or dorsal aspects of the glans, exceeding half the width of the glans or penile girth with the complete vanishing of the glans closure in most cases. Megameatus is usually associated with the abnormal meatal position as hypospadiac, orthotopic, or epispadic. Additionally, megameatus may be associated with a normally intact or deficient prepuce. Consequently, we had four categories of megameatus, and the intact prepuce orthotopic megameatus subcategory has not been described before. Megameatus was also detected with deficient prepuce, and this was considered a hypospadiac variant. CONCLUSION: Megameatus is diagnosed precisely with penile biometry and is classified into 4 groups: hypospadiac, epispadic, and orthotopic or central, either with or without intact prepuce. This classification is applicable for expansion to other centers.


Assuntos
Circuncisão Masculina , Epispadia , Hipospadia , Masculino , Lactente , Criança , Humanos , Pênis/anormalidades , Hipospadia/cirurgia , Prepúcio do Pênis , Uretra/anormalidades
9.
Int J Impot Res ; 35(3): 309-322, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36997741

RESUMO

Demographically diverse surveys in the United States suggest that 5-10% of non-voluntarily circumcised American males wish that they had not been circumcised. Similar data are unavailable in other countries. An unknown proportion of circumcised males experience acute circumcision-related distress; some attempt to regain a sense of bodily integrity through non-surgical foreskin restoration. Their concerns are often ignored by health professionals. We conducted an in-depth investigation into foreskin restorers' lived experiences. An online survey containing 49 qualitative and 10 demographic questions was developed to identify restorers' motivations, successes, challenges, and experiences with health professionals. Targeted sampling was employed to reach this distinctive population. Invitations were disseminated to customers of commercial restoration devices, online restoration forums, device manufacturer websites, and via genital autonomy organizations. Over 2100 surveys were submitted by respondents from 60 countries. We report results from 1790 fully completed surveys. Adverse physical, sexual, emotional/psychological and self-esteem impacts attributed to circumcision had motivated participants to seek foreskin restoration. Most sought no professional help due to hopelessness, fear, or mistrust. Those who sought help encountered trivialization, dismissal, or ridicule. Most participants recommended restoration. Many professionals are unprepared to assist this population. Circumcision sufferers/foreskin restorers have largely been ill-served by medical and mental health professionals.


Assuntos
Circuncisão Masculina , Prepúcio do Pênis , Masculino , Humanos , Estados Unidos , Prepúcio do Pênis/cirurgia , Motivação , Saúde Mental , Circuncisão Masculina/métodos , Circuncisão Masculina/psicologia , Comportamento Sexual
10.
Toxics ; 11(2)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36851034

RESUMO

Cisplatin (Cis) is a potent chemotherapeutic agent; however, it is linked with oxidative stress, inflammation, and apoptosis, which may harmfully affect the brain. Hypericum perforatum L. (HP L.) is a strong medicinal plant, but its hydrophobic polyphenolic compounds limit its activity. Therefore, our study aimed to investigate the neuroprotective action of HP L. and its nanoemulsion (NE) against Cis-induced neurotoxicity. The prepared HP.NE was subjected to characterization. The droplet size distribution, surface charge, and morphology were evaluated. In addition, an in vitro dissolution study was conducted. Compared to Cis-intoxicated rats, HP L. and HP.NE-treated rats displayed improved motor activity and spatial working memory. They also showed an increase in their antioxidant defense system and a reduction in the levels of pro-inflammatory cytokines in the brain. Moreover, they showed an increase in the expression levels of the PON-3 and GPX genes, which are associated with a reduction in the brain levels of COX-2 and TP-53. These findings were confirmed by reducing the immunohistochemical expression of nuclear factor kappa (NF-ƘB) and enhanced Ki-67 levels. In conclusion, HP L. is a promising herb and could be used as an adjuvant candidate to ameliorate chemotherapeutic-induced neurotoxicity. Moreover, HP.NE has superior activity in lessening Cis-induced oxidative stress, inflammation, and apoptosis in brain tissue.

11.
J Appl Toxicol ; 43(8): 1119-1129, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36807594

RESUMO

Acute kidney injury (AKI) is a very critical cause of death in the whole world. Lipopolysaccharide (LPS) induces kidney damage by activating various deleterious inflammatory and oxidative pathways. Protocatechuic acid, a natural phenolic compound, has shown to exert beneficial effects against oxidative and inflammatory responses. The study aimed to clarify the nephroprotective activity of protocatechuic acid in LPS-induced acute kidney damage in mice. Forty male Swiss mice were allocated in four groups as follows: normal control group; LPS (250 µg/kg, ip)-induced kidney injury group; LPS-injected mice treated with protocatechuic acid (15 mg/kg, po), and LPS-injected mice treated with protocatechuic acid (30 mg/kg, po). Significant toll-like receptor 4 (TLR-4)-mediated activation of IKBKB/NF-κB and MAPK/Erk/COX-2 inflammatory pathways has been observed in kidneys of mice treated with LPS. Oxidative stress was revealed by inhibition of total antioxidant capacity, catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and NAD(P)H quinone oxidoreductase (NQO1) enzyme along with increased nitric oxide level. In parallel, focal inflammatory effects were shown in between the tubules and glomeruli as well as in the perivascular dilated blood vessels at the cortex affecting the normal morphology of the kidney tissues of LPS-treated mice. However, treatment with protocatechuic acid reduced LPS-induced changes in the aforementioned parameters and restored normal histological features of the affected tissues. In conclusion, our study uncovered that protocatechuic acid has nephroprotective effects in mice with AKI through opposing different inflammatory and oxidative cascades.


Assuntos
Injúria Renal Aguda , NF-kappa B , Masculino , Animais , Camundongos , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Quinase I-kappa B/metabolismo , Regulação para Baixo , Sistema de Sinalização das MAP Quinases , Rim , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo
12.
Biomed Pharmacother ; 153: 113526, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076607

RESUMO

The prevalence of metabolic syndrome (MetS) has been rising alarmingly and it has now become a global concern causing an enormous economic burden on the health care system. MetS is generally linked to complications in lipid metabolism, oxidative stress and low grade inflammation. The aim of the current study was to evaluate the effect of rosuvastatin, co-enzyme Q10 (CoQ10), and their combination on blood pressure, blood sugar, dyslipidemia, and liver function in rats with MetS induced by high fructose and high fat diet (HF-HFD) and the possible underlying mechanism. Oral administration of rosuvastatin (10 mg/kg/day), CoQ10 (10 mg/kg/day) and their combination for 4 weeks in HF-HFD-fed rats elevated serum high density lipoprotein and reduced glutathione. On the other hand, treatment with rosuvastatin, CoQ10 or their combination decreased the serum levels of malondialdehyde, triglycerides, total cholesterol, and low density lipoprotein-cholesterol as well as systolic blood pressure, body weight and fasting blood glucose level. In addition, the drugs or their combination declined serum pro-inflammatory cytokines, namely tumor necrosis factor-α and interleukin-1ß. In conclusion, our results showed that rosuvastatin or CoQ10 protected against HF-HFD-induced MetS through the regulation of dyslipidemia, elevated blood glucose, elevated blood pressure, antioxidant defenses and inflammatory response. Rosuvastatin or CoQ10 also alleviated the impairment of liver function that was induced by HF-HFD. Interestingly, CoQ10 augmented rosuvastatin's effect in ameliorating MetS, via exerting synergistic modulatory effects on oxidative stress and inflammation. Thus, rosuvastatin and CoQ10 combination therapy may have possible applications in ameliorating metabolic disorders.


Assuntos
Dislipidemias , Síndrome Metabólica , Animais , Glicemia/metabolismo , Colesterol/farmacologia , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/tratamento farmacológico , Frutose , Humanos , Inflamação/tratamento farmacológico , Síndrome Metabólica/metabolismo , Estresse Oxidativo , Ratos , Rosuvastatina Cálcica/efeitos adversos
13.
Polymers (Basel) ; 14(14)2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35890659

RESUMO

A new three-dimensional (3D) boundary element method (BEM) strategy was developed to solve fractional-order thermo-elastoplastic ultrasonic wave propagation problems based on the meshless moving least squares (MLS) method. The temperature problem domain was divided into a number of circular sub-domains. Each node was the center of the circular sub-domain surrounding it. The Laplace transform method was used to solve the temperature problem. A unit test function was used in the local weak-form formulation to generate the local boundary integral equations, and the inverse Laplace transformation method was used to find the transient temperature solutions. Then, the three-dimensional elastoplastic problems could be solved using the boundary element method (BEM). Initial stress and strain formulations are adopted, and their distributions are interpolated using boundary integral equations. The effects of the fractional-order parameter and anisotropy are investigated. The proposed method's validity and performance are demonstrated for a two-dimensional problem with excellent agreement with other experimental and numerical results.

14.
Sci Rep ; 12(1): 6760, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35474097

RESUMO

The primary goal of this article is to propose a new fractional boundary element technique for solving nonlinear three-temperature (3 T) thermoelectric problems. Analytical solution of the current problem is extremely difficult to obtain. To overcome this difficulty, a new numerical technique must be developed to solve such problem. As a result, we propose a novel fractional boundary element method (BEM) to solve the governing equations of our considered problem. Because of the advantages of the BEM solution, such as the ability to treat problems with complicated geometries that were difficult to solve using previous numerical methods, and the fact that the internal domain does not need to be discretized. As a result, the BEM can be used in a wide variety of thermoelectric applications. The numerical results show the effects of the magnetic field and the graded parameter on thermal stresses. The numerical results also validate the validity and accuracy of the proposed technique.

15.
BMC Urol ; 22(1): 50, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379191

RESUMO

BACKGROUND: A wide spectrum of complications are reported after male circumcision (MC), the non-aesthetic complications are well known, but the pigmentary complications scale are not reported precisely. METHODS: This is a prospective cohort study of 550 circumcised boys; aged from 6 months to 14 years (62% aged 5 years) who were examined and appropriately investigated for the incidence of pigmentary complications after circumcision. Most diagnoses were clinically, but dermoscopy was done for 17 case and a skin biopsy for 14 cases. Patients with personal or family history of vitiligo, or congenital nevi were excluded. Available hospital records details and parents' statements were revised. The main outcome measures are the incidence of different pigmentary complications and circumcision details; data were analyzed by a non-parametric tests including the Mann-Whitney U test. RESULTS: 69 cases had 72 confirmed pigmentary complications discovered at 2-36 months after commencement of circumcision (mean 18). 48 cases had pigmentary complications directly related to MC, 11 cases were probably related and 10 unrelated to MC. The most common lesion is the circular hyperpigmented scar (29 cases); liner hyperpigmented scar in 13, spotted exogenous melanosis in 18 cases, melanocytic nevi (7), hypopigmentation diagnosed in 3 cases, but kissing nevus is the rarest finding (2). Topical corticosteroid was tried in 15 cases, surgical excision of pigmented scar were done for 19 cases, local laser used for 4 resistant cases and reassurance with follow up for the rest. CONCLUSION: Pigmentary complications after male circumcision are not rare and its management is challenging.


Assuntos
Circuncisão Masculina , Neoplasias Cutâneas , Pré-Escolar , Circuncisão Masculina/efeitos adversos , Humanos , Incidência , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos
16.
Materials (Basel) ; 15(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35269059

RESUMO

The main aim of this paper was to develop an advanced processing method for analyzing of anisotropic thermoelastic metal and alloy discs with holes. In the boundary element method (BEM), the heat impact is expressed as an additional volume integral in the corresponding boundary integral equation. Any attempt to integrate it directly will necessitate domain discretization, which will eliminate the BEM's most distinguishing feature of boundary discretization. This additional volume integral can be transformed into the boundary by using branch-cut redefinitions to avoid the use of additional line integrals. The numerical results obtained are presented graphically to show the effects of the transient and steady-state heat conduction on the quasi-static thermal stresses of isotropic, orthotropic, and anisotropic metal and alloy discs with holes. The validity of the proposed technique is examined for one-dimensional sensitivity, and excellent agreement with finite element method and experimental results is obtained.

17.
J Enzyme Inhib Med Chem ; 37(1): 895-911, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35345960

RESUMO

A novel series of 4-(4-Methoxyphenyl)-2-(methylthio)pyrimidine-5-carbonitrile was developed linked to an aromatic moiety via N-containing bridge and then evaluated for their cytotoxic activity against MCF-7 and K562 cell lines. Seven compounds exhibited the highest activity against both cell lines where compounds 4d and 7f were the most active against K562 cell line. Exploring their molecular mechanisms by enzyme inhibition assay on PI3Kδ/γ and AKT-1 showed that compound 7f was promising more than 4d with IC50 = 6.99 ± 0.36, 4.01 ± 0.55, and 3.36 ± 0.17 uM, respectively. Also, flowcytometric analysis revealed that 7f caused cell cycle arrest at S-phase followed by caspase 3 dependent apoptosis induction. Mechanistically, compound 7f proved to modulate the expression of PI3K, p-PI3K, AKT, p-AKT, Cyclin D1, and NFΚß. Furthermore, in-vivo toxicity study indicated good safety profile for 7f. These findings suggest that the trimethoxy derivative 7f has strong potential as a multi-acting inhibitor on PI3K/AKT axis targeting breast cancer and leukaemia.


Assuntos
Antineoplásicos , Leucemia , Nitrilas , Pirimidinas , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3 , Ciclina D1 , Humanos , Células K562 , Leucemia/tratamento farmacológico , Leucemia/patologia , Células MCF-7 , NF-kappa B , Nitrilas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Pirimidinas/farmacologia
18.
Obes Surg ; 32(2): 457-462, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34981323

RESUMO

BACKGROUND: Obesity is a growingly impacting human health concern. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for morbid obesity. However, the general anesthesia (GA) used in this major surgery has its documented drawbacks in obese patients with high risk. On the other hand, combined thoracic spinal-epidural anesthesia (CTSEA), a modern regional anesthesia procedure, has the advantages of both spinal and epidural anesthesia but without their shortcomings. This prospective study is a case experience that assesses the feasibility of CTSEA as an anesthesia option for laparoscopic sleeve gastrectomy (LSG). METHODS: A total of 100 patients were recruited for LSG as a management procedure for morbid obesity, which was performed under CTSEA. Perioperative events, functional parameters, and patients' satisfaction scores were recorded. RESULTS: Our prospective study showed successful use of CTSEA in 99% of the patients, except for one patient (1%) in whom CTSEA was converted into GA due to severe pain and anxiety. Few adverse events occurred and were managed accordingly. The satisfaction score revealed that 94% of the patients were satisfied. CONCLUSIONS: CTSEA was a successful anesthetic alternative procedure for LSG surgery.


Assuntos
Anestesia Epidural , Laparoscopia , Obesidade Mórbida , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Redução de Peso
19.
Int J Gynaecol Obstet ; 158(2): 424-431, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34674270

RESUMO

OBJECTIVE: To validate the use of placenta accreta risk-antepartum (PAR-A) score as a predictive tool of clinical outcomes of placenta accreta spectrum (PAS). METHODS: This is a prospective study, conducted in six PAS specialized centers in six different countries. The study was conducted between October 1, 2020 and March 31, 2021. Women who were provisionally diagnosed with PAS during pregnancy were considered eligible. A machine-learning-based PAR-A score was calculated. Diagnostic performance of the PAR-A score was evaluated using a receiver operating characteristic curve, for perioperative massive blood loss and admission to intensive care unit (ClinicalTrials.gov identifier NCT04525001). RESULTS: Of 97 eligible women, 86 were included. PAS-associated massive blood loss occurred in 10 patients (11.63%). Median PAR-A scores of massive blood loss in the current cohort were 8.9 (interquartile range 6.9-14.1). In predicting massive blood loss, the area under the curve of PAR-A scores was 0.85 (95% confidence interval [CI] 0.74-0.95), which was not significantly different from the original cohort (P = 0.2). PAR-A score prediction of intensive care unit admission was slightly higher compared with the original cohort (0.88, 95% CI 0.81-0.95; P = 0.06). CONCLUSION: PAR-A score is a novel scoring system of PAS outcomes, which showed external validity based on current data.


Assuntos
Placenta Acreta , Placenta Prévia , Estudos de Coortes , Feminino , Humanos , Placenta , Placenta Acreta/diagnóstico , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
20.
J Matern Fetal Neonatal Med ; 35(25): 6644-6653, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34233555

RESUMO

INTRODUCTION: Placenta accreta spectrum is a major obstetric disorder that is associated with significant morbidity and mortality. The objective of this study is to establish a prediction model of clinical outcomes in these women. MATERIALS AND METHODS: PAS-ID is an international multicenter study that comprises 11 centers from 9 countries. Women who were diagnosed with PAS and were managed in the recruiting centers between 1 January 2010 and 31 December 2019 were included. Data were reanalyzed using machine learning (ML) models, and 2 models were created to predict outcomes using antepartum and perioperative features. ML model was conducted using python® programing language. The primary outcome was massive PAS-associated perioperative blood loss (intraoperative blood loss ≥2500 ml, triggering massive transfusion protocol, or complicated by disseminated intravascular coagulopathy). Other outcomes include prolonged hospitalization >7 days and admission to the intensive care unit (ICU). RESULTS: 727 women with PAS were included. The area under curve (AUC) for ML antepartum prediction model was 0.84, 0.81, and 0.82 for massive blood loss, prolonged hospitalization, and admission to ICU, respectively. Significant contributors to this model were parity, placental site, method of diagnosis, and antepartum hemoglobin. Combining baseline and perioperative variables, the ML model performed at 0.86, 0.90, and 0.86 for study outcomes, respectively. Ethnicity, pelvic invasion, and uterine incision were the most predictive factors in this model. DISCUSSION: ML models can be used to calculate the individualized risk of morbidity in women with PAS. Model-based risk assessment facilitates a priori delineation of management.


Assuntos
Placenta Acreta , Feminino , Humanos , Gravidez , Placenta Acreta/cirurgia , Placenta Acreta/diagnóstico , Placenta , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Aprendizado de Máquina , Estudos Retrospectivos , Histerectomia/métodos
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