RESUMO
BACKGROUND: Lupus nephritis (LN) is a common serious presentation of systemic lupus erythematosus. Cyclophosphamide (CYC) and mycophenolate mofetil (MMF) are listed as the first-line drugs in induction therapy for LN. OBJECTIVE: This study aimed to compare high- and low-dose CYC in a cohort of Egyptian LN patients. PATIENTS AND METHODS: The data of 547 patients with class III/IV active LN who received CYC as induction therapy were retrospectively analyzed. Whereas 399 patients received 6monthly 0.5-1â¯g/m2 CYC doses, 148 patients received six biweekly 500â¯mg CYC doses. Demographic data, laboratory test results, and disease activity index were recorded and compared at presentation and at 6, 12, 18, 24, and 48 months of follow-up. RESULTS: After 48 months, the proportion of patients maintaining normal creatinine levels was higher in the group receiving induction therapy with high-dose CYC (67.9%, 60.4%, pâ¯= 0.029), and these patients also had higher proteinuria remission at 36 (26.6%, 14.8%, pâ¯= 0.014) and 48 months (24.3%, 12.8%, pâ¯= 0.006). Comparison of patient outcomes according to both induction and maintenance therapy showed the best results in patients who received high-dose CYC and continued MMF as maintenance therapy. CONCLUSION: High- and low-dose CYC are comparable in early phases of treatment. However, after a longer duration of follow-up, high-dose CYC was associated with higher remission rates in the current cohort.
Assuntos
Nefrite Lúpica , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Egito/epidemiologia , Resultado do Tratamento , Ciclofosfamida/efeitos adversos , Ácido Micofenólico/efeitos adversos , Indução de RemissãoRESUMO
BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.
Assuntos
Injúria Renal Aguda , Alopurinol , Meios de Contraste , Nefropatias Diabéticas , Linagliptina , Substâncias Protetoras , Humanos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Nefropatias Diabéticas/classificação , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Linagliptina/administração & dosagem , Linagliptina/uso terapêutico , Estudos Prospectivos , Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Meios de Contraste/efeitos adversos , Quimioprevenção/métodos , Quimioterapia Combinada , Acetilcisteína/administração & dosagem , Acetilcisteína/uso terapêutico , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/efeitos adversos , Substâncias Protetoras/uso terapêutico , Solução Salina/administração & dosagem , Solução Salina/uso terapêuticoRESUMO
INTRODUCTION: Direct-acting antiviral agents (DAAs) have modified the management of chronic hepatitis C virus (HCV) infection, including HCV-related cryoglobulinemic vasculitis (CryoVas). However, patients might experience vasculitis relapse, and no reliable predictors of CryoVas relapse after sustained virologic response (SVR) have been established. We aimed to describe HCV-CryoVas relapse rates and factors associated with it. METHODS: An international multicenter cohort where patients with HCV-CryoVas from Egypt, France, and Italy treated with DAA were analyzed retrospectively. Factors associated with relapse-free survival were evaluated in a multivariate-adjusted model. RESULTS: Of 913 patients, 911 (99.8%) obtained SVR. After 35 months of the median follow-up, 798 patients (87.4%) had sustained remission of vasculitis, while 115 (12.6%) experienced CryoVas relapse. By the time of relapse, skin involvement was present in 100%, renal involvement in 85.2%, and peripheral neuropathy in 81.7%. Relapses were treated with glucocorticoids in 90.9%, associated with plasma exchange, cyclophosphamide, or rituximab in 50%, 37.3%, and 6.4%, respectively. The cumulative incidence of CryoVas relapse was 0.7% (95% CI 0.3-1.4), 12.3% (95% CI 10.2-14.6), and 13.1% (95% CI 11.0-15.5) at 12, 24, and 36 months after DAA treatment, respectively. Independent baseline risk factors associated with CryoVas relapse were male sex, skin ulcers, kidney involvement at baseline, and peripheral neuropathy at the end of DAA treatment. Death occurred in 11 relapsers, mainly due to infections. DISCUSSION: A substantial proportion of patients with CryoVas experience relapse after DAA-induced SVR. Relapses are moderate-to-severe and affect survival after 24 months, mainly due to infections. Independent risk factors for relapse or death were found.
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Crioglobulinemia , Hepatite C Crônica , Hepatite C , Vasculite , Antivirais/uso terapêutico , Crioglobulinemia/complicações , Crioglobulinemia/etiologia , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Masculino , Recidiva , Estudos Retrospectivos , Resposta Viral Sustentada , Vasculite/tratamento farmacológicoRESUMO
Tolperisone and etodolac were proven to have synergistic effect for patients of acute low back pain associated with musculoskeletal spasm. In this work, a specific, highly sensitive and reproducible analytical method was developed and validated for the simultaneous determination of tolperisone and etodolac in human plasma using liquid chromatography-tandem mass spectrometric technique. Liquid-liquid extraction was optimized for sample preparation. Zorbax C8 column (3.5 µm, 50 × 4.6 mm) was used, carrying a mobile phase mixture of 10.0 mM ammonium formate:acetonitrile (40:60, v/v) pH 3.8, running in an isocratic mode. Chlorzoxazone acted as an internal standard. Sample volume of injection was 5.0 µL, and analysis was achieved within 2.5 min. Detection and quantitation were performed by electrospray ionization mass spectrometry using the multiple-reaction monitoring mode. The proposed method could determine the analytes in the range of concentration 0.5-200.0 ng mL-1 for tolperisone and 0.05-20.0 µg mL-1 for etodolac. Findings of inter- and intraday precisions were ≤12.3% with accuracy of ±5.0%. Pharmacokinetics study for the two drugs after oral administration of healthy human volunteers was achieved with the aid of application of the developed study.
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Tolperisona , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Etodolac , Humanos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
AIM: Lupus nephritis (LN) is one of the most serious complications of SLE. Tregs (Regulatory T lymphocytes) are thought to play a part in the pathogenesis of SLE. According to recent research, Foxp3, a Treg identification marker, plays a significant role in the pathogenesis of SLE. This study aimed to compare the urinary Foxp3 mRNA levels of patients with active and inactive forms of LN and healthy control subjects to see whether it played a role in disease activity. METHODS: We measured FOXP3 messenger RNA (mRNA) expression in the urine of 50 people with active LN, 50 people with inactive lupus, and 50 healthy people. RESULTS: We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (22.93 ± 4.13 vs 5.66 ± 0.47 vs 0.57 ± 0.15copy; P < 0.001).Urinary FOXP3 mRNA level significantly correlated with SLEDAI (0.000057) In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (< 0.00001). CONCLUSION: We concluded that urinary FOXP3 mRNA is elevated in patients with active LN and that it is linked to the SLEDAI and the severity of the disease. FOXP3 mRNA in urine sediment may be used as a non-invasive biomarker for evaluating the severity of LN and risk stratification.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Biomarcadores , Egito , Fatores de Transcrição Forkhead/química , Fatores de Transcrição Forkhead/genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , RNA MensageiroRESUMO
BACKGROUND: The incidence of subdural hematoma (SDH) in chronic maintenance hemodialysis (CMH) patients may change over time, along with the evolving characteristics of the underlying populations. METHODS: We conducted a retrospective, single-center study at Cairo University hospitals, assessing the incidence, associated risk factors, and outcomes of nontraumatic SDH in CMH patients between January 2006 and January 2019. RESULTS: Out of 1217 CMH patients, nontraumatic SDH was diagnosed in 41 (3.37%) during the study, increasing with the enrollees' age but stable over the observation period and translating into an annual incidence rate of 28 per 1000 patients per year. SDH patients were likely to use central venous catheters, reported pruritis and history of bone fractures, and had higher phosphorus, parathyroid hormone, and alkaline phosphatase values (p < 0.001); however, there was no association with atrial fibrillation or use of anticoagulants. In the SDH cohort (n = 41), six patients did not need surgical intervention and 13 patients died before becoming surgically fit for intervention; mortality correlated with ischemic heart disease (p = 0.033) and the presence of atrial fibrillation or chronic anticoagulation with warfarin (p < 0.0001 for both), among others. Twenty-two patients received surgical operations and of these 2 died postoperatively; overall patient mortality was 12/41 (29.27%) at 30 days and 15/41 (36.59%) at 1 year. CONCLUSION: Our study demonstrated a striking enrichment for underlying comorbidities in those patients developing SDH and a high risk of immediate mortality. The benefit of chronic anticoagulation therapy should be carefully weighed against the risk of CNS bleed in MHD patients.
Assuntos
Hematoma Subdural/epidemiologia , Hematoma Subdural/etiologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/epidemiologia , Egito/epidemiologia , Feminino , Hematoma Subdural/mortalidade , Hematoma Subdural/prevenção & controle , Humanos , Incidência , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Diálise Renal/mortalidade , Estudos Retrospectivos , Fatores de RiscoRESUMO
STATEMENT OF PROBLEM: Tooth preparations for ceramic crowns require precision and accuracy, which may be influenced by the choice of dental handpiece. However, comparisons of the accuracy of tooth preparations made with traditional air-turbine handpieces and electric handpieces are lacking. PURPOSE: The purpose of this in vitro study was to evaluate operator preferences and tooth preparation performance by using electric and air-turbine handpieces with self-reported preferences, sound levels, surface roughness, and the fit of the crown produced. MATERIAL AND METHODS: Twenty dentists were asked to use the air-turbine or the electric handpiece. Feedback on the noise, weight, feel of grip, flexibility, and tooth preparation in general was scored according to a visual analog scale (VAS). Additionally, the dentists were asked to complete a questionnaire on their handpiece preference. The noise of the 2 handpieces was measured by using a precision sound level meter. The surface roughness of 10 teeth was measured by using a profilometer. The other 18 teeth were prepared to measure the marginal and internal fit of ceramic crowns by the replica technique. The VAS scores of operator preferences were analyzed with the Wilcoxon signed ranks test. Decibel levels were analyzed with the Mann-Whitney U test. The McNemar test was used to compare the ratio of preferred handpiece. The surface roughness and marginal and internal fit were analyzed with the independent t test to determine significant differences (all α=.05). RESULTS: The electric handpiece was heavier, had a poorer grip feel, was less flexible (P<.001), produced lower noise and better feeling of the tooth preparation in general (P<.001), and was preferred in the finishing stage for its greater smoothness (P<.05). The noise produced by the electric handpiece was lower during both idling and tooth preparation at 15-cm, 30-cm, and 45-cm distances (P<.01). The electric handpiece produced surface roughness values (Sa) similar to those of the air-turbine handpiece (P>.05). No significant differences were noted for the marginal and internal crown fit between the air-turbine handpiece and electric handpiece groups (P>.05). CONCLUSIONS: Despite its heavier weight, poorer grip feel, and less flexibility, the electric handpiece emitted lower noise, produced better feeling of the tooth preparation in general, and was preferred in the finishing step of tooth preparation for its greater smoothness than the air-turbine handpiece. The surface roughness of the prepared teeth and the crown fit between the tooth and ceramic crown were not affected by the air-turbine or electric handpiece.
Assuntos
Equipamentos Odontológicos de Alta Rotação , Dente , Coroas , Porcelana Dentária , Humanos , Preparo do DenteRESUMO
OBJECTIVE: Sclerostin is an osteocyte-secreted protein that downregulates bone formation by blocking the Wnt/ß-catenin signaling pathway. Sclerostin can be induced by inflammation, and high levels have been reported in patients with proteinuria and renal impairment. Studies evaluating the role of sclerostin in systemic lupus erythematosus (SLE) patients are scarce. This study aims to measure serum sclerostin in SLE patients and correlate its level with bone biomarkers and disease activity, particularly in lupus nephritis and arthritis. Finally, we evaluated factors that may predict sclerostin concentrations. METHODS: This cross-sectional, case-control study was conducted from May 2017 to April 2018. Serum sclerostin was measured by enzyme-linked immunosorbent assay in 100 SLE patients, including 50 patients with current lupus nephritis and 27 patients with current arthritis, as well as in 50 healthy controls. Correlation analysis of serum sclerostin with demography, bone biomarkers, and disease activity in SLE patients was carried out. RESULTS: Sclerostin levels were significantly elevated in SLE patients, particularly those with lupus nephritis, compared with healthy controls. Higher levels were identified in patients without arthritis compared with those with; however, the former group had more proteinuria and renal impairment. Significant correlations were observed between sclerostin levels and serum creatinine, proteinuria, consumed C3 and C4 complement, and corrected Ca. Using multiple linear regression, proteinuria was the only significant predictor for serum sclerostin in SLE patients. CONCLUSIONS: This study is the first to report that serum sclerostin is associated with proteinuria in SLE patients and could be used as a valuable biomarker for lupus nephritis.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Biomarcadores , Estudos de Casos e Controles , Estudos Transversais , Egito/epidemiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnósticoRESUMO
Low serum 25 hydroxyvitamin D (25 OH D) is common among chronic kidney disease (CKD) patients. This cross-sectional study is looking for the different factors associated with serum 25 OH D among pre-dialysis CKD. 1624 adult stage 3-5 CKD patients were studied beside 200 normal control subjects. All candidates were tested for body mass index (BMI), estimated glomerular filtration rate (eGFR), calcium (Ca), phosphorus (P), parathormone (PTH), 25 OH D, albumin, and uric acid (UA), and urine albumin/creatinine ratio (ACR). Multivariate linear regression analysis was done to determine predictors of 25 OH D. 98.6% of CKD patients have inadequate level of 25 OH D vs 48% of normal subjects. Serum 25 OH D was significantly lower in CKD patients (mean ± S.D = 16.54 ± 5.8 vs 37.79 ± 3.58 ng/mL for CKD vs control group respectively, p < .001). Serum level of 25 OH D has significant positive correlation with Ca (r = 0.337, p < .001), and significant negative correlation with P, PTH, UA, and ACR (r = -0.440, -0. 679, -0.724, and -0.781respectively, p < .001 in all). The independent predictors of 25 OH D were Ca, P, UA, PTH, and ACR (R square = 0.7, ß = -0.087, -0.226, -0.313, -0.253, and -0.33 respectively, p < .001 in all). In conclusion, pre-dialysis CKD patients frequently suffer low 25 OH D. Among the different abnormalities related to CKD, urine albumin excretion rate and UA are the most important predictors of 25 OH D in these patients.
Assuntos
Albuminúria/urina , Insuficiência Renal Crônica/complicações , Ácido Úrico/sangue , Deficiência de Vitamina D/diagnóstico , Vitamina D/análogos & derivados , Adolescente , Adulto , Albuminas/análise , Albuminúria/sangue , Albuminúria/etiologia , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Adulto JovemRESUMO
In this study, some of new thiophenyl thienopyrimidinone derivatives 2-15 were prepared and tested as anti-cancer agents by using thiophenyl thieno[2,3-d]pyrimidinone derivative 2 as a starting material, which was prepared from cyclization of ethyl ester derivative 1 with formamide. Treatment of 2 with ethyl- chloroacetate gave thienopyrimidinone N-ethylacetate 3, which was reacted with hydrazine hydrate or anthranilic acid to afford acetohydrazide 4 and benzo[d][1,3]oxazin-4-one 5, respectively. Condensation of 4 with aromatic aldehydes or phenylisothiocyanate yielded Schiff base derivatives 6,7, and thiosemicarbazise 10, which were treated with 2-mercaptoacetic acid or chloroacetic acid to give the corresponding thiazolidinones 8, 9, and phenylimino-thiazolidinone 11, respectively. Treatment of 4 with ethylacetoacetate or acetic acid/acetic anhydride gave pyrazole 12 and acetyl acetohydrazide 13 derivatives, respectively. The latter compound 13 was reacted with ethyl cycno-acetate or malononitrile to give 14 and 15, respectively. In this work, we have studied the anti-cancer activity of the synthesized thienopyrimidinone derivatives against MCF-7 and MCF-10A cancer cells. Furthermore, in vivo experiments showed that the synthesized compounds significantly reduced tumor growth up to the 8th day of treatment in comparison to control animal models. Additionally, the synthesized derivatives showed potential inhibitory effects against pim-1 kinase activities.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Pirimidinonas/síntese química , Pirimidinonas/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Pirimidinonas/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A series of 16-(α-alkoxyalkane)-17-hydrazino-estra-1(10),2,4-trien[17,16-c]-3-ol (3a-l) and estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol derivatives (4a-d) were synthesized from corresponding arylidines 2a,b which was prepared from estrone 1 as starting material. Condensation of 1 with aldehydes gave the corresponding arylidine derivatives 2a,b which were treated with hydrazine derivatives in alcohols to give the corresponding derivatives 3a-l, respectively. Additionally, treatment of 2a,b with methyl- or phenylhydrazine in ethanolic potassium hydroxide afforded the corresponding N-substituted pyrazoline derivatives 4a-d, respectively. All these derivatives showed potent anti-ovarian cancer both in vitro and in vivo. The mechanism of anti-ovarian cancer was suggested to process via topoisomerase II and V600EBRAF inhibition.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Estrona/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Modelos Animais de Doenças , Estrona/análogos & derivados , Feminino , Humanos , Camundongos , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Inibidores da Topoisomerase II/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Healthcare spending has become a grave concern to national budgets worldwide, and to a greater extent in low-income countries. Brain tumors are a serious disease that affects a significant percentage of the population, and thus proper allocation of healthcare provisions for these patients to achieve acceptable outcomes is a must. The authors reviewed patients undergoing craniotomy for tumor resection at their institution for the preceding 3 months. All the methods used for preoperative planning, intraoperative management, and postoperative care of these patients were documented. Compromises to limit spending were made at each stage to limit expenditure, including low-resolution MRI, sparse use of intraoperative monitoring and image guidance, and lack of dedicated postoperative neurocritical ICU. This study included a cohort of 193 patients. The average cost from diagnosis to discharge was $1795 per patient (costs are expressed in USD). On average, there was a mortality rate of 10.5% and a neurological morbidity rate of 14%, of whom only 82.2% improved on discharge or at follow-up. The average length of stay at the hospital for these patients was 9.09 days, with a surgical site infection rate of only 3.5%. The authors believe that despite the great number of financial limitations facing neurosurgical practice in low-income countries, surgery can still be performed with reasonable outcomes.
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Neoplasias Encefálicas/cirurgia , Craniotomia , Custos de Cuidados de Saúde , Procedimentos Neurocirúrgicos/economia , Neoplasias Encefálicas/mortalidade , Países em Desenvolvimento , Egito , Mortalidade Hospitalar , Humanos , Tempo de Internação , Monitorização Intraoperatória , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Pobreza , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
Insulin resistance (IR) is very common among chronic kidney disease (CKD) patients. Disturbance in mineral and bone metabolism (MBD) seems to play a role in the pathogenesis of insulin resistance. Fibroblast growth factor-23 (FGF23) is evolving as the most important link between MBD and many pathologic sequences of CKD. The aim was to evaluate IR in pre-dialysis CKD patients looking for a possible association to mineral metabolism among CKD patients. A total of 100 stage 3-5 CKD patients were selected beside 20 normal control subjects. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess IR in selected cases. Both groups were compared for fasting blood glucose (FBG), fasting blood insulin (FBI), HOMA-IR, estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25 hydroxy vitamin D (25 OH vit D), parathormone (PTH), and uric acid (UA). Correlation study between HOMA_IR and different studied parameters was performed. HOMA-IR is significantly higher in CKD (8.87 ± 3.48 vs. 3.97 ± 0.34 in CKD vs. control, respectively, p < .001). In addition CKD patients have significantly higher FGF23 (235 ± 22.96 vs. 139 ± 12.3 pg/mL, p < .001), PTH (76.9 ± 15.27 vs. 47.9 ± 2.52 pg/mL, p < .001), P (4.3 ± 0.67 vs. 3.6 ± 0.23 mg/dL, p < .001), and UA (5 ± 1.22 vs. 4.85 ± 0.48 mg/dL, p < .001) and significantly lower Ca (8.2 ± 0.3 vs. 8.9 ± 0.33 mg/dL, p < .001), and 25 (OH) vit D (17 ± 5.63 vs. 37 ± 3.43 ng/mL, p < .001). Stepwise linear regression analysis revealed that BMI, GFR, Ca, P, and FGF23 were the only significant predictors of HOMA IR. Increased IR in CKD is a consequence of the uremic status and is intimately associated with disturbed phosphate metabolism and FGF23. Further studies are needed to look for an underlying mechanism.
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Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Resistência à Insulina , Fosfatos/metabolismo , Insuficiência Renal Crônica/metabolismo , Adulto , Glicemia , Índice de Massa Corporal , Cálcio/sangue , Cálcio/metabolismo , Estudos de Casos e Controles , Creatinina/urina , Jejum , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Fosfatos/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Ácido Úrico/sangue , Adulto JovemRESUMO
The formation of metal chelates with various ligands may lead to the production of fluorescent chelates or enhance the fluorescence of the chelating agent. This paper describes two sensitive, selective and computer-solved methods, namely, zero order (SF) and second-derivative synchronous spectrofluorimetry (SDSFS) for nano-quantitation of two carbapenems; meropenem (MP) and ertapenem (EP). The methods are based on the chelation of MP with Tb3+ and EP with Zr4+ in buffered organic medium at pH 4.0 to produce fluorescent chelates. In the zero order method, the relative synchronous fluorescence intensity is measured at 327.0 nm at Δλ = 70.0 and 100.0 nm for MP and EP, respectively. The second method utilizes a second-derivative technique to enhance the method selectivity and emphasize a stability-indicating approach. The peak amplitudes (2 D) of the second-derivative synchronous spectra were estimated to be 333.06 and 330.06 nm for MP and EP, respectively. The proposed synchronous spectrofluorimetric methods were validated according to the International Conference on Harmonization (ICH) guidelines and applied successfully for the analysis of MP and EP in pure forms, pharmaceutical vials and in synthetic mixtures with different degradants of both drugs. Under optimum conditions, the mole-ratio method was applied and the co-ordination ratios of MP-Tb3+ and EP-Zr4+ chelates were found to be 1:1 and 1:3. The formation constants for the chelation complexes were evaluated using the Benesi-Hildebrand's equation; the free energy change (ΔG) was also calculated. The results indicated that EP-Zr4+ was more stable than the MP-Tb3+ chelate. Moreover, the developed methods were found to be selective and inexpensive for quantitative determination of both drugs in quality control laboratories at nano-levels.
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Quelantes/química , Tienamicinas/química , beta-Lactamas/análise , Ertapenem , Meropeném , Estrutura Molecular , Espectrometria de Fluorescência , Térbio/química , Termodinâmica , Zircônio/química , beta-Lactamas/químicaRESUMO
A series of substituted pyrazole, triazole and thiazole derivatives (2-13) were synthesized from 1-(naphtho[1,2-d]thiazol-2-yl)hydrazine as starting material and evaluated as androgen receptor antagonists and anti-prostate cancer agents. The newly synthesized compounds showed potent androgen receptor antagonists and anti-prostate cancer activities with low toxicity (lethal dose 50 (LD50)) comparable to Bicalutamide as reference drug. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, and MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD50 values and pharmacological activities of the synthesized compounds are reported.
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Antagonistas de Receptores de Andrógenos/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Pirazóis/farmacologia , Pirimidinas/farmacologia , Tiazóis/farmacologia , Triazóis/farmacologia , Animais , Células CHO , Linhagem Celular , Linhagem Celular Tumoral , Cricetulus , Humanos , Dose Letal Mediana , MasculinoRESUMO
A series of new 3-substituted-7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives were synthesized as antimicrobial agents using 7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methyl-4H-pyrido[3',2':4,5]thieno[3,2-d]-[1,3]oxazin-4-one as a starting compound. Its condensation with substituted aniline derivatives or phenyl hydrazine gave the corresponding N-substituted derivatives. Treatment of the starting compound with hydrazine hydrate afforded the corresponding N-amino derivative, which was reacted with substituted phenylisocyanate and phenylisothiocyanate derivatives to give the corresponding semicarbazides and thiosemicarbazide derivatives. All the newly synthesized compounds were evaluated for their antimicrobial activities in comparison to streptomycin and fusidic acid as positive controls. The structure assignments of the new compounds are based on chemical and spectroscopic evidence.
Assuntos
Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Piridinas/síntese química , Pirimidinonas/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Hidrazinas/síntese química , Hidrazinas/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Oxazinas/síntese química , Oxazinas/química , Piridinas/química , Piridinas/farmacologia , Pirimidinonas/química , Pirimidinonas/farmacologiaRESUMO
The study presents a first electrochemical method for the determination of the immunomodulator drug Baricitinib (BARI), crucial in managing COVID-19 patients requiring oxygen support. A unique electrode was developed by modifying graphite carbon nickel nanoparticles (NiNPs) with functionalized multiwalled carbon nanotubes (f.MWCNTs), resulting in nanohybrids tailored for highly sensitive BARI detection. Comparative analysis revealed the superior electrocatalytic performance of the nanohybrid-modified electrode over unmodified counterparts and other modifications, attributed to synergistic interactions between f.MWCNTs and nickel nanoparticles. Under optimized conditions, the sensors exhibited linear detection within a concentration range from 4.00 × 10-8 to 5.56 × 10-5 M, with a remarkably low detection limit of 9.65 × 10-9 M. Notably, the modified electrode displayed minimal interference from common substances and demonstrated high precision in detecting BARI in plasma and medicinal formulations, underscoring its clinical relevance and potential impact on COVID-19 treatment strategies.
Assuntos
Azetidinas , COVID-19 , Técnicas Eletroquímicas , Nanotubos de Carbono , Níquel , Purinas , Pirazóis , SARS-CoV-2 , Sulfonamidas , Nanotubos de Carbono/química , Sulfonamidas/química , Níquel/química , Pirazóis/química , Humanos , Purinas/química , Azetidinas/química , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Tratamento Farmacológico da COVID-19 , Teste de Materiais , Fatores Imunológicos/química , Fatores Imunológicos/uso terapêutico , Tamanho da Partícula , Catálise , Materiais Biocompatíveis/química , Limite de DetecçãoRESUMO
BACKGROUND: Patients with Type 2 diabetes mellitus (T2DM) have decreased bone health. We aimed to investigate serum levels of bone turnover markers (BTMs) (markers of bone formation and bone resorption) and bone mineral density (BMD) at three sites (lumber, neck femur, and total femur) in middle-aged men with type 2 diabetes and to analyze the relationship between them. Also to evaluate serum osteoglycin as a novel marker and its relation to BTMs, BMD, and diabetic status. METHODS: We recruited seventy-eight patients with T2DM and thirteen non-diabetic, male volunteers as a control group. BMD was measured using a DEXA scan. BTMs (carboxy-terminal crosslinking telopeptide of type 1 collagen [CTX] and procollagen type 1 N propeptide [P1NP]), osteoglycin, PTH, and vitamin D were estimated. Data was compared among subjects and statistical analysis was performed. RESULTS: Most of the patients were having normal BMD with no significant difference between patients and the controls. BTMs and osteoglycin were significantly higher and vitamin D was significantly lower in the diabetic patients. Serum osteoglycin was positively correlated with DEXA Neck Femur (r = 0.233; p-value < 0.05). CONCLUSION: Body mass index and Serum osteoglycin have a significant positive effect on BMD. Both markers of bone formation and bone resorption were increased indicating a state of increased bone turnover in T2DM.
RESUMO
BACKGROUND: Pain is the major cause of disability in disc induced lumbosacral radiculopathy (LSR) and is related to neurotrophins mainly brain derived neurotrophic factor (BDNF). However, to our knowledge evaluating serum BDNF in disc induced LSR has not been reported before. This study was done to investigate serum BDNF in LSR patients and its relation to pain severity and functional disability. METHODS: This case-control study included 40 disc induced LSR patients and 40 age and sex matched healthy subjects. All patients were subjected to neurological examination, electrophysiological evaluation, pain severity assessment using numerical rating scale (NRS) and functional disability assessment using Modified Oswestry Low Back Pain Disability Index (ODI) and Maine-Seattle Back Questionnaire (MSBQ). According to Douleur neuropathique 4 (DN4) questionnaire, patients were divided into those with neuropathic pain and those with non-neuropathic pain. Serum BDNF was measured by enzyme-linked immunosorbent assay in all participants. RESULTS: Serum BDNF was significantly higher in LSR patients than in healthy controls (U=272.5, P<0.001). Moreover, serum BDNF was significantly higher in those with neuropathic pain compared to those with non-neuropathic pain (U=35, P=0.03). Serum BDNF had a significant positive correlation with NRS score among those with acute pain (rs=0.537, P=0.026), however there was no significant correlation among those with chronic pain. Furthermore, BDNF had no significant correlation with modified ODI and MSBQ. CONCLUSION: Increased serum BDNF may be associated with neuropathic pain and acute pain severity in disc induced LSR. However, it may not be related to chronic pain severity or functional disability.