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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.
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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.
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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.
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Azetidinas , COVID-19 , Técnicas Electroquímicas , Nanotubos de Carbono , Níquel , Purinas , Pirazoles , SARS-CoV-2 , Sulfonamidas , Nanotubos de Carbono/química , Sulfonamidas/química , Níquel/química , Pirazoles/química , Humanos , Purinas/química , Azetidinas/química , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Tratamiento Farmacológico de COVID-19 , Ensayo de Materiales , Factores Inmunológicos/química , Factores Inmunológicos/uso terapéutico , Tamaño de la Partícula , Catálisis , Materiales Biocompatibles/química , Límite de DetecciónRESUMEN
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.
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Nefritis Lúpica , Humanos , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Estudios Retrospectivos , Egipto/epidemiología , Resultado del Tratamiento , Ciclofosfamida/efectos adversos , Ácido Micofenólico/efectos adversos , Inducción de RemisiónRESUMEN
AIM: Low skeletal muscle mass in ICU patients is associated with poor clinical outcome. Ultrasonography is a noninvasive method that can measure muscle thickness at the bedside. We aimed at studying the relation of the ultrasonography measured muscle layer thickness (MLT) at time of ICU admission with the patients' outcome namely mortality, duration of mechanical ventilation (MV) and ICU length of stay (LOS). In addition to define the best cut-off values that can predict mortality in medical ICU patients. METHOD: this observational prospective study was conducted on 454 adult critically ill patients admitted to the medical ICU of a university hospital. At the time of admission, MLT of the anterior mid-arm and lower 1/3 thigh were assessed using ultrasonography with and without transducer compression. The clinical scores for assessment of disease severity; Acute Physiology and Chronic Health Evaluation score (APACHE-II) and Sequential Organ Failure Assessment score (SOFA) in addition to nutrition risk; modified Nutrition Risk in Critically ill score (mNUTRIC) were estimated for all patients. ICU LOS, duration on MV and mortality were reported. RESULTS: The mean age of our patients was 51 years ± 19. The ICU mortality rate was 36.56%. The baseline MLT was negatively associated with APACHE-II, SOFA and NUTRIC scores but not with duration of MV or ICU-LOS. The non-survivors had lower values of baseline MLT. A cut-off value of 0.895 cm (AUC: 0.649, 95% CI of 0.595-0.703) using the mid-arms as a reference point with maximum probe compression showed the highest sensitivity (90%) to predict mortality compared to other techniques however with low specificity (22%). CONCLUSION: the baseline ultrasonography measured mid-arm MLT is a sensitive risk assessment tool that can reflect disease severity and predict ICU mortality.
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Enfermedad Crítica , Estado Nutricional , Adulto , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Unidades de Cuidados Intensivos , MúsculosAsunto(s)
Diabetes Mellitus Tipo 2 , Glomerulonefritis , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Hipoglucemiantes/farmacología , Glomerulonefritis/tratamiento farmacológicoRESUMEN
BACKGROUND: Amelioration of proteinuria is one of main treatment targets in patients with glomerulonephritis, yet the remission rates are suboptimal. AIM OF THE STUDY: To examine the effect of the sodium-glucose transporter 2 inhibitor (empagliflozin) on proteinuria and kidney function progression, in patients with glomerulonephritis not due to diabetic kidney diseases. SUBJECTS AND METHODS: Fifty patients were recruited. The entry criteria were diagnosis of glomerulonephritis, and proteinuria (proteinuria ≥ 500 mg/g) in spite of the use of the maximal tolerated dose of RAAS blocking agents together with specific immunosuppression treatment regimens. Group 1 (Empagliflozin arm): 25 patients who received 25 mg of empagliflozin once daily for 3 months as add-on to their regular treatment protocol (RAAS blockers and immunosuppression). Group 2 (Placebo arm): 25 patients treated with RAAS blockers and immunosuppression. The primary efficacy endpoints were the change in creatinine eGFR, and proteinuria 3 months after starting treatment. RESULTS: Progression of proteinuria was lower with empagliflozin as compared to placebo (odds ratio, 0.65; 95% CI, 0.55 to 0.72, p = 0.002). Decline in eGFR was lower with empagliflozin as compared to placebo; however, this was statistically not significant (odds ratio, 0.84; 95% CI, 0.82 to 1.2, p = .31). The percentage change in proteinuria was greater with empagliflozin as compared to placebo (median, - 77 (- 97-105) vs - 48 (- 80-117). CONCLUSION: Empagliflozin has a favorable effect on amelioration of proteinuria in patients with glomerulonephritis. Empagliflozin has tendency to preserve kidney function in patients with glomerulonephritis as compared to placebo; however, longer term studies are required.
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Diabetes Mellitus Tipo 2 , Glomerulonefritis , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Resultado del Tratamiento , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Tasa de Filtración Glomerular , Riñón , Glomerulonefritis/complicaciones , Glomerulonefritis/tratamiento farmacológico , Método Doble CiegoRESUMEN
Designing new, verified methodologies with a focus on sustainability, analytical efficiency, simplicity, and the environment has become a major priority for pharmaceutical quality control units. In this way, sustainable and selective separation-based methodologies were designed and validated for the concurrent estimation of amiloride hydrochloride (AML), hydrochlorothiazide (HCT) and timolol maleate (TIM) in their fixed dose formulation (Moducren® Tablets) along with hydrochlorothiazide potential impurities, salamide (DSA) and chlorothiazide (CT). The first method is a high performance thin layer chromatographic method (HPTLC-densitometry). The first developed method employed silica gel HPTLC F254 plates as stationary phase using a chromatographic developing system composed of ethyl acetate-ethanol-water-ammonia (8.5:1:0.5:0.3, by volume). The separated drug bands were densito-metrically measured at 220.0 nm for AML, HCT, DSA and CT and at 295.0 nm for TIM. The linearity was assessed over a wide concentration range, 0.5-10 µg/band, 1.0-16.0 µg/band and 1.0-14 µg/band for AML, HCT and TIM, in order and 0.05-1.0 µg/band for each of DSA and CT. The second method is capillary zone electrophoresis (CZE). The electrophoretic separation was achieved using background electrolyte (BGE), borate buffer 40.0 mM with pH 9.0 ± 0.2, at applied voltage of + 15 kV with on-column diode array detection at 200.0 nm. The method linearity was reached over the concentration range of 20.0-160.0 µg/mL, 10.0-200.0 µg/mL, 10.0-120.0 µg/mL for AML, HCT and TIM, respectively and 10.0-100.0 µg/mL for DSA. The suggested methods were optimized to achieve best performance and validated agreeing with the ICH guidelines. Assessment of methods' sustainability and greenness was performed using different greenness assessment tools.
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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.
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Lesión Renal Aguda , Alopurinol , Medios de Contraste , Nefropatías Diabéticas , Linagliptina , Sustancias Protectoras , Humanos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Alopurinol/administración & dosificación , Alopurinol/uso terapéutico , Nefropatías Diabéticas/clasificación , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/diagnóstico , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Linagliptina/administración & dosificación , Linagliptina/uso terapéutico , Estudios Prospectivos , Insuficiencia Renal Crónica/clasificación , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Medios de Contraste/efectos adversos , Quimioprevención/métodos , Quimioterapia Combinada , Acetilcisteína/administración & dosificación , Acetilcisteína/uso terapéutico , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/efectos adversos , Sustancias Protectoras/uso terapéutico , Solución Salina/administración & dosificación , Solución Salina/uso terapéuticoRESUMEN
The kidney represents an important target of systemic inflammation. Its involvement in monogenic and multifactorial autoinflammatory diseases (AIDs) vary from peculiar and relatively frequent manifestations to some rare but severe features that may end up requiring transplantation. The pathogenetic background is also very heterogeneous ranging from amyloidosis to non-amyloid related damage rooted in inflammasome activation. Kidney involvement in monogenic and polygenic AIDs may present as renal amyloidosis, IgA nephropathy, and more rarely as various forms of glomerulonephritis (GN), namely segmental glomerulosclerosis, collapsing glomerulopathy, fibrillar, or membranoproliferative GN. Vascular disorders such as thrombosis or renal aneurysms and pseudoaneurysms may be encountered in patients with Behcet's disease. Patients with AIDs should be routinely assessed for renal involvement. Screening with urinalysis, serum creatinine, 24-h urinary protein, microhematuria, and imaging studies should be carried out for early diagnosis. Awareness of drug-induced nephrotoxicity, drug-drug interactions as well as addressing the issue of proper renal adjustment of drug doses deserve a special mention and should always be considered when dealing with patients affected by AIDs. Finally, we will explore the role of IL-1 inhibitors in AIDs patients with renal involvement. Targeting IL-1 may indeed have the potential to successfully manage kidney disease and improve long-term prognosis of AIDs patients.
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Amiloidosis , Glomerulonefritis por IGA , Enfermedades Autoinflamatorias Hereditarias , Humanos , Riñón/patología , Glomerulonefritis por IGA/patología , Amiloidosis/patología , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Enfermedades Autoinflamatorias Hereditarias/patología , Interleucina-1RESUMEN
Two selective stability-indicating procedures were adopted for the quantification of Solifenacin succinate (SOL) along with its acid degradant, in its powder form or in pharmaceutical tablet. Under stress conditions, the acid degradation pathway of SOL was investigated, its official impurity (SOL imp-A) was obtained as the possible acid degradation product, also. A densitometric technique based on the separation of SOL from SOL imp-A employing HPTLC plates prelaminated with silica gel 60 F254 as the stationary phase and a developing solution containing methanol:chloroform:ammonia (8:1:1, v/v/v) and UV scanning of the developed bands at 220 nm. Linear regression analysis data for the calibration plot of SOL showed perfect linear relationships throughout the range of concentration 10-60 µg/band. A reversed phase C18 analytical column (4.6 × 250 mm, 5 µm) was also used to separate the mixture at a flow rate of 1 mL/min, using acetonitrile:0.05 M phosphate buffer (70:30, v/v) as the mobile phase and phosphoric acid to set pH = 3.5. Quantification was obtained at 220 nm using peak area and linear calibration curve across a concentration range of 10-70 µg/mL. The recommended procedures were applied to the existing dosage form, and they generated satisfactory results.
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Succinato de Solifenacina , Cromatografía en Capa Delgada/métodos , Reproducibilidad de los Resultados , Cromatografía Líquida de Alta Presión/métodos , ComprimidosRESUMEN
INTRODUCTION: Systemic lupus erythematosus is an autoimmune multisystem disease; renal affection is one of its most common manifestations. The effect of environmental factors on lupus nephritis flares is not fully understood. METHODS: This is a retrospective study that included 200 patients with lupus nephritis flares. All patients had confirmed diagnosis of lupus nephritis on histopathological examination. Lupus nephritis flares were defined by either (1) nephritic flare: defined as increased proteinuria or serum creatinine concentration; abnormal urinary sediment or a reduction in creatinine clearance, or (2) proteinuria flare defined as persistent increase in proteinuria > 0.5-1.0 g/day after achieving complete remission; doubling to > 1 g/day after achieving partial remission. The time of renal flare (month of the year) was recorded to determine the effect of seasonal variation on lupus nephritis flares. RESULTS: The median age for the patients was 33 years (IQR = 13); 92% of patients were females. The median duration of lupus was 7 years (IQR = 6). The median serum creatinine was 1.4 mg/dl, median serum urea level was 32, and median UPCR was 2.4 gm/dl. The highest incidence of flares occurred in June (14%) and July (12.5%) (p = 0.003). CONCLUSION: Seasonal pattern of LN flare was observed in our study in Egyptian cohort of patients, with most flares observed during meteorological summertime. Larger studies are needed to confirm this seasonal pattern. Key Points ⢠Flares of lupus nephritis are common in patients with systemic lupus erythromatosus. ⢠A seasonal pattern of flares of lupus nephritis was observed in our study. This seasonal pattern has been observed by previous studies in variable ethnicities and variable climatic circumstances.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Femenino , Humanos , Adolescente , Masculino , Nefritis Lúpica/patología , Estaciones del Año , Estudios Retrospectivos , Creatinina , Egipto/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/diagnóstico , Proteinuria/etiologíaRESUMEN
One of the most significant consequences of systemic lupus erythematosus (SLE) is lupus nephritis (LN). Visfatin, an adipokine that is significantly expressed in visceral fat and is a marker of endothelial dysfunction in chronic kidney disease, has multiple proinflammatory actions. We aimed to evaluate the state of serum visfatin in SLE patients and to detect its possible correlation with the disease's activity and effects on the kidney affection. Fifty patients with active LN, 50 patients with inactive lupus, and 50 healthy people had their serum visfatin levels tested. Chemical and immunological markers of SLE and LN were measured. The SLE Disease Activity Index (SLEDAI) was used to measure the disease's activity. Renal biopsies from the LN subgroup were collected and classified using the modified classification of the World Health Organization. The serum visfatin of patients with active LN was significantly greater than that of inactive lupus patients and the healthy controls (20.56 ± 1.07 ng/mL, 16.77 ± 1.02 ng/mL, and 9.96 ± 1.46 ng/mL, P <0.001). SLEDAI and serum visfatin levels were shown to be significantly correlated (P = 0.000057). Serum visfatin levels were likewise significantly correlated with the index of histological activity in the active group (P <0.00001). Serum visfatin was raised in individuals with active LN and was related to the SLEDAI and disease severity scores. Serum visfatin could be utilized as a noninvasive biomarker for evaluating the severity of LN and risk stratification of the risk.
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Biomarcadores , Nefritis Lúpica , Nicotinamida Fosforribosiltransferasa , Humanos , Nicotinamida Fosforribosiltransferasa/sangre , Nefritis Lúpica/sangre , Nefritis Lúpica/diagnóstico , Biomarcadores/sangre , Femenino , Adulto , Masculino , Egipto , Estudios de Casos y Controles , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Citocinas/sangre , Índice de Severidad de la Enfermedad , Adulto Joven , Valor Predictivo de las Pruebas , Persona de Mediana EdadRESUMEN
Endothelial dysfunction in patients with diabetic nephropathy is caused by nontraditional factors in addition to common risk factors (e.g., hypertension) in people with normal kidney function. These nontraditional factors include factors involved in mineral bone disease in these patients. One of these factors is fibroblast growth factor 23 (FGF-23). We aimed to evaluate the relationship between flow-mediated dilatation (FMD) as a measure of endothelial dysfunction and FGF-23. This was a cross-sectional observational study that was conducted on 100 diabetic patients (Group I: 50 patients with nephropathy; Group II: 50 patients without nephropathy) and 50 healthy volunteers (Group III). Serum levels of intact FGF-23, interleukin-6, intact parathyroid hormone, and 25-hydroxyvitamin D (25-(OH)Vit D); estimated insulin resistance; and FMD were evaluated. FGF-23 was significantly higher in Group I (median: 101 pg/mL) and Group II (median: 101 pg/mL) than in Group III (median: 4 pg/mL) (P <0.001), but FGF-23 was not significantly different between Groups I and II. A significant positive correlation was found between serum levels of FGF-23 and phosphorus in Group I. A significant negative correlation was found between serum levels of FGF-23 and 25-(OH)Vit D in Group II. However, FGF-23 failed to show a significant correlation with FMD in patients with diabetic nephropathy. Our data suggest another factor that rises earlier than FGF-23 in diabetic nephropathy and causes endothelial dysfunction.
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Nefropatías Diabéticas , Enfermedades Vasculares , Humanos , Estudios Transversales , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/etiología , Egipto , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de FibroblastosRESUMEN
BACKGROUND: Many of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI. OBJECTIVE: We looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome. CASES AND METHODS: This is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away. RESULTS: Serum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P<0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. Survivors were younger in age (median 55.5 vs. 60 years, P<0.04), had lower AST (30.5 vs. 58 units, P<0.001), had higher platelet count (206 vs 162×109/L, P<0.001), otherwise, there was no significant difference in any of the other parameters between survivors and patients that were lost. Serum sclerostin had strong correlation with FGF23 in group I (r=0.99, P<0.001) and group II (r=1, P<0.001). Homa IR had positive correlation with serum sclerostin (r=0.148, P=0.014) and serum FGF23 (r=0.142, P=0.018) in group I. CONCLUSION: Sclerostin is intimately related to FGF23. Sclerostin level increases in AKI patients. Both sclerostin and FGF23 might increase insulin resistance but have no impact on FMD. Neither sclerostin nor FGF23 interfere with AKI outcome.
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Lesión Renal Aguda , Resistencia a la Insulina , Insuficiencia Renal Crónica , Biomarcadores , Proteína C-Reactiva , Calcio , Creatinina , Estudios Transversales , Factores de Crecimiento de Fibroblastos , Humanos , Interleucina-6 , Minerales/metabolismo , Hormona Paratiroidea , Fósforo , Urea , Ácido Úrico , Vitamina DRESUMEN
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 , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida , Etodolaco , Humanos , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodosRESUMEN
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 , Hepatitis C Crónica , Hepatitis C , Vasculitis , Antivirales/uso terapéutico , Crioglobulinemia/complicaciones , Crioglobulinemia/etiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferones/uso terapéutico , Masculino , Recurrencia , Estudios Retrospectivos , Respuesta Virológica Sostenida , Vasculitis/tratamiento farmacológicoRESUMEN
Background: Many of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI.ObjectiveWe looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome.Cases and methodsThis is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away.ResultsSerum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P<0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. (AU)
Antecedentes: Muchas de las anomalías de los metabolitos minerales que se encuentran en el riñón de los pacientes con enfermedad renal crónica (ERC) también se asociaron con lesión renal aguda (IRA). En la última década, se ha descubierto que la esclerostina afectaba íntimamente al metabolismo mineral óseo en pacientes con ERC. No se sabe nada sobre la esclerostina en la LRA.ObjetivoBuscamos el nivel sérico de esclerostina en pacientes con IRA en comparación con los niveles normales en sujetos de control, y si hay un impacto en el trastorno metabólico, la función endotelial o el resultado clínico.Casos y métodosEste es un estudio observacional transversal de casos y controles de 219 casos de IRA (grupo I) además de 219 sujetos de control normales de la misma edad (grupo II). Todos los casos del grupo I se hallaban en cuidados intensivos por sepsis; 86 tenían ERC aguda (grupo Ib), mientras que 133 tenía de novo AKI (grupo Ia). Todos los sujetos estudiados se sometieron a una estimación de la esclerostina sérica, hormona paratiroidea (PTH), 25 hidroxi vitamina D (25 OH vit D), factor de crecimiento de fibroblastos 23 (FGF23), proteína C reactiva (CRP), interleucina 6 (IL6), evaluación del modelo homeostático para resistencia a la insulina (Homa IR), además del hemograma completo de rutina, pruebas de función renal y hepática, suero calcio y fósforo, y vasodilatación de la arteria braquial (FMD) mediada por flujo. El seguimiento de los casos del grupo I se realizó hasta que se recuperaron o fallecieron.ResultadosEsclerostina sérica, PTH, FGF23, fósforo, PCR, IL6, HOMA IR, creatinina, urea, ácido úrico, ALT, AST y recuento de glóbulos blancos (WBC) fueron significativamente más altos mientras que el suero calcio, 25 OH vit D, hemoglobina, recuento de plaquetas y fiebre aftosa fueron significativamente más bajos en el grupo I en comparación con el grupo II (p<0,001 en total). (AU)
Asunto(s)
Humanos , Nefrología , Receptores de Factores de Crecimiento de Fibroblastos , Sepsis , Resistencia a la InsulinaRESUMEN
BACKGRΟUND: Fοur rapid, smart, and easy tο apply spectrοphοtοmetric methοds were developed fοr the estimatiοn οf sοlifenacin succinate (SΟL) with its acid-induced degradation prοduct. ΟBJECTIVE: Development οf stability-indicating, smart, sensitive, cheap spectrοphοtοmetric methοds fοr determinatiοn οf SΟL in the presence οf its acid degradate. METHΟDS: Methοd A is a dual wavelength methοd where twο wavelengths were selected (262 and 289 nm) and utilized tο determine SΟL in the presence οf its acid degradate. Methοd B involves develοping the first derivative (1D) οf the absοrptiοn spectra. Peak signal was detected at 276 nm. Methοd C is a ratiο difference methοd where the drug is determined by the difference in signal between twο selected wavelengths, at 240 and 259 nm. Methοd D is dependent οn measuring the peak signal οf the first derivative οf the ratiο spectra (1DD) at 269 nm. RESULTS: Calibratiοn curves οf the suggested methοds exhibited linearity. The selectivity οf the suggested methοds were ascertained using different labοratοry-prepared mixtures οf SΟL with its acid degradate, indicating specificity οf SΟL with accepted recοvery values. The suggested methοds have been successfully applied tο the analysis οf SΟL in its pharmaceutical dοsage fοrm withοut the invοlvement οf additives. CΟNCLUSIΟN: The presented wοrk applied fοur resοlutiοn techniques, based οn absοrbance, derivative, and/οr ratiο spectra, fοr the analysis οf SΟL in the presence οf its acid degradate. HIGHLIGHTS: The study οf degradatiοn pathways οf drugs is οf great impοrtance. Hence, acid hydrοlysis οf SΟL was achieved and then SΟL was determined alοng with its acid degradate.
Asunto(s)
Preparaciones Farmacéuticas , Ácido Succínico , Estabilidad de Medicamentos , EspectrofotometríaRESUMEN
Endothelial dysfunction is evident in systemic lupus erythematosus (SLE). Pro-inflammatory adipokines are involved in endothelial derangement and premature atherosclerosis, particularly in lupus nephritis (LN). This study aimed to investigate the impact of LN on endothelial function by estimating the serum levels of adiponectin, leptin, visfatin, and homeostatic model assessment-insulin resistance (HOMA-IR) and calculating the flow-mediated dilatation (FMD) of the brachial artery. This is a case-control study in which 190 systemic lupus patients who were fulfilling the American College of Rheumatology revised classification were enrolled. The patients were divided into 100 LN patients and 90 lupus non-nephritis patients. Demographic data, clinical parameters, and SLE activity were reported. Serum adiponectin, leptin, visfatin, and HOMA-IR were measured. The endothelial dysfunction was assessed by calculating the FMD of the brachial artery. The mean age of participants was 25.62 ± 5.81 years. Elevated levels of adiponectin, leptin, visfatin, and HOMA-IR were observed in LN cases (12.2 ± 0.3, 20.1 ± 0.5, 16.8 ± 0.1, and 12.0 ± 3.8, respectively) compared to non-nephritis cases (12.2 ± 0.3, 8.5 ± 0.5, 16.8 ± 0.5, and 9.0 ± 3.8, respectively) with a more reduced FMD percentage in LN cases with a statistical significance. Brachial artery FMD is negatively correlated with lipid profile, adipokines, and HOMA. Visfatin has better sensitivity (82.1%) and specificity (81%) with the area under a curve of 0.893, compared to other biomarkers. LN patients are characterized by impaired endothelial function. Elevated serum adiponectin, visfatin, and HOMA-IR were significantly correlated with poor FMD of the brachial artery. Visfatin has a better performance in detecting atherosclerosis.