RESUMEN
BACKGROUND: Complications associated with liver cirrhosis are various and potentially fatal. The treatment options to counteract hepatic decompensation are limited. Therefore, the study aimed to explore the use of allopurinol in preventing the recurrence of liver cirrhosis-related complications. METHODS: One hundred patients with hepatic decompensation were randomized into 1:1 ratio to receive either allopurinol 300 mg or placebo tablets once daily for 6 months. The primary endpoint was the incidence of cirrhosis-related complications (overt ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, and hepatic encephalopathy). RESULTS: Six months following treatment, allopurinol reduced the relative risk (RR) of any first complication experienced after enrollment by 56% (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.27-0.62); P Ë .001). Allopurinol decreased the RR of overt ascites by 67% (HR 0.33; 95% CI, 0.0098-0.94); P = .039] and reduced the RR of spontaneous bacterial peritonitis by about 75% (HR 0.25; 95% CI, 0.05-0.76; P = .01). Likewise, allopurinol was linked to an 80% reduction in the RR of developing hepatorenal syndrome (HR 0.2; 95% CI, 0.04-0.87; P = .033). CONCLUSION: Allopurinol significantly decreased the recurrence of overall liver cirrhosis-related complications. Therefore, allopurinol may constitute a promising agent for patients with hepatic decompensation. These positive outcomes could be a result of its ability to reduce bacterial translocation and inflammation. GOV IDENTIFIER: NCT005545670.
Asunto(s)
Várices Esofágicas y Gástricas , Síndrome Hepatorrenal , Peritonitis , Humanos , Alopurinol/uso terapéutico , Várices Esofágicas y Gástricas/complicaciones , Ascitis/etiología , Ascitis/prevención & control , Síndrome Hepatorrenal/tratamiento farmacológico , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/prevención & control , Hemorragia Gastrointestinal/etiología , Cirrosis Hepática/complicaciones , Peritonitis/prevención & control , Peritonitis/complicacionesRESUMEN
As a synthetic analog of codeine, tramadol is often prescribed to treat mild to moderate pains. This study was designed to estimate and compare the histological effect of tramadol on testes of both juvenile and adult male albino mice. A total number of 40 healthy male albino mice were classified into two main groups as follows: group I (juvenile group, includes 20 mice aged three weeks) subdivided equally into group Ia (control group received isotonic saline) and group Ib (tramadol-treated group received 40 mg/kg/d tramadol orally for 30 days); group II (adult group, includes 20 mice aged two months) subdivided equally into group IIa (control group received isotonic saline) and group IIb (tramadol-treated group). Juvenile and adult tramadol-treated groups showed numerous testicular changes, including blood vessels congestion, widening of intercellular spaces, vacuolization in interstitial tissues, luminal germ cells exfoliation, and increased expression of caspase-3 that indicated cellular apoptosis. In the ultrastructural examination, spermatogenic cells degenerated with the frequent appearance of apoptotic cells. Sertoli cells showed vacuolations, large lipid droplets, and disrupted intercellular cell junctions. These observed testicular changes were markedly observed in the juvenile group. Testicular abnormalities and apoptotic changes can be caused by tramadol administration. These abnormalities are more common in juvenile mice.
RESUMEN
This study compared the cardioprotective action of mesenchymal stem cells (MSCs) and PUFAs in a rat model of gentamicin (GM)-induced cardiac degeneration. Male Wistar albino rats were randomized into four groups of eight rats each: group I (control group), group II (gentamicin-treated rats receiving gentamicin intraperitoneally (IP) at dose of 100 mg/kg/day for 10 consecutive days), group III (gentamicin and PUFA group receiving gentamicin IP at dose of 100 mg/kg/day for 10 consecutive days followed by PUFAs at a dose of 100 mg/kg/day for 4 weeks), and group IV (gentamicin and MSC group receiving gentamicin IP at dose of 100 mg/kg/day followed by a single dose of MSCs (1 × 106)/rat IP). Cardiac histopathology was evaluated via light and electron microscopy. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA), caspase-3 (apoptosis), Bcl2, and Bax expression was performed. Moreover, cardiac malonaldehyde (MDA) content, catalase activity, and oxidative stress parameters were biochemically evaluated. Light and electron microscopy showed that both MSCs and PUFAs had ameliorative effects. Their actions were mediated by upregulating PCNA expression, downregulating caspase-3 expression, mitigating cardiac MDA content, catalase activity, and oxidative stress parameters. MSCs and PUFAs had ameliorative effects against gentamicin-induced cardiac degeneration, with MSCs showing higher efficacy compared to PUFAs.
RESUMEN
BACKGROUND AND OBJECTIVE: Paclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer. PATIENTS AND METHODS: This randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group (n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group (n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months. Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t-test, Mann-Whitney U test, and chi-square test. RESULTS: As compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9th and 12th weeks of paclitaxel intake (p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin (p < 0.05) as compared to baseline data and placebo. CONCLUSION: Alpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03908528.
Asunto(s)
Neoplasias de la Mama , Síndromes de Neurotoxicidad , Enfermedades del Sistema Nervioso Periférico , Ácido Tióctico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Doxorrubicina , Femenino , Humanos , Neurotensina/sangre , Síndromes de Neurotoxicidad/etiología , Paclitaxel , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Estudios Prospectivos , Ácido Tióctico/uso terapéutico , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVES: To investigate the anti-tumor activity and tolerability of celecoxib as an adjuvant therapy for patients with metastatic colorectal cancer (CRC). METHODS: In this randomized controlled study, 54 patients with metastatic CRC were randomized into 2 groups; the control group (n=28) which received 6 cycles of folinic acid, fluorouracil and irinotecan (FOLFIRI) regimen (5-flourouracil, leucovorin, irinotecan), and the celecoxib group (n=26) which received 6 cycles of FOLFIRI regimen plus celecoxib 200 mg twice daily. The study duration was 3 months. Patients were assessed at baseline and at the end of intervention through the Response Evaluation Criteria in Solid Tumors objective response rate (ORR) and through evaluating the serum concentrations of vascular endothelial growth factor (VEGF), soluble factor-related apoptosis (sFAS), sFAS ligand (sFASL), and epithelial neutrophil-activating peptide -78 (ENA-78/CXCL5). Common Terminology Criteria for Adverse Events version 6.0 was used for evaluating drug-related toxicity. RESULTS: After intervention, celecoxib/FOLFIRI arm showed significant elevation in ORR as compared to FOLFIRI arm (p=0.001). As compared to FOLFIRI arm, celecoxib/FOLFIRI arm showed significantly lower VEGF (p<0.001), CXCL5 (p<0.001), and sFASL (p<0.001) serum levels and significantly higher sFAS serum level and sFAS/FASL ratio (p<0.001). Furthermore, celecoxib/FOLFIRI arm showed significantly higher progression-free survival and one-year overall survival when compared to FOLFIRI arm. CONCLUSION: Celecoxib plus chemotherapy may represent an effective and safe synergetic protocol for patients with metastatic CRC.Clinicaltrial.gov ID:NCT03645187.
Asunto(s)
Neoplasias Colorrectales , Factor A de Crecimiento Endotelial Vascular , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/uso terapéutico , Celecoxib/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo , Humanos , LeucovorinaRESUMEN
Objective: This study aimed at evaluating the effects of candesartan and ramipril on liver fibrosis in patients with chronic hepatitis C. Methods: This randomized controlled prospective study involved 64 patients with chronic hepatitis C and liver fibrosis. Participants were randomized into 3 groups: group I (control group; nâ¯=â¯21), members of which received traditional therapy only; group 2 (ramipril group; nâ¯=â¯21), members of which received traditional therapy plus 1.25 mg/d oral ramipril; and group 3 (candesartan group; nâ¯=â¯22), members of which received traditional therapy plus 8 mg/d oral candesartan. Patients were assessed at baseline and 6 months after intervention through measuring of liver stiffness (Fibro-Scan; Echosens, Paris, France); evaluation of the serum levels of hyaluronic acid and transforming growth factor beta-1; and calculation of indices of liver fibrosis, including fibrosis index based on the 4 factors and aspartate transaminase-to-platelet-ratio index. Data were analyzed using paired t test and 1-way ANOVA followed by Tukey's honest significant difference test for multiple pairwise comparisons. Results: At baseline, the 3 study groups were statistically similar in demographic and laboratory data. After treatment, the 3 study groups showed significant decrease in liver stiffness, serum levels of hyaluronic acid and transforming growth factor beta-1, and indices of liver fibrosis compared with baseline data (P < 0.001). Six months after treatment, patients taking ramipril and candesartan showed significant improvement in all measured parameters compared with the control group. Additionally, the candesartan-treated group showed significant decrease in liver stiffness, biomarkers, and indices of liver fibrosis compared with ramipril recipients. Conclusions: The administration of ramipril and candesartan in patients with chronic hepatitis C with hepatic fibrosis was well tolerated and effective in improving liver fibrosis. angiotensin II receptor 1 (AT1) antagonist candesartan maintained antifibrotic effects more effectively than ramipril and may represent a safe and effective therapeutic strategy for liver fibrosis in patients with chronic liver diseases. ClinicalTrials.gov identifier: NCT03770936. (Curr Ther Res Clin Exp. 2022; 83:XXX-XXX) © 2022 Elsevier HS Journals, Inc.
RESUMEN
BACKGROUND: There are differences of opinion about both the most effective combined therapeutic strategy and the clinical benefit of inhaled corticosteroids in nonasthmatic patients with chronic obstructive pulmonary disease. Furthermore, many inflammatory cytokines are reportedly correlated with severity of the disease. OBJECTIVES: To compare the effectiveness of long acting ß-agonistâ¯+â¯long-acting muscarinic antagonist (LABAâ¯+â¯LAMA) versus LABAâ¯+â¯inhaled corticosteroid and LAMAâ¯+â¯inhaled corticosteroid in nonasthmatic patients with moderate-to-severe chronic obstructive pulmonary disease. To assess the changes that occurred in plasma concentrations of tumor necrosis factor α, fibrinogen, and interleukin 6, and correlate these with disease activity. METHODS: In this pilot study, 45 nonasthmatic patients with moderate to severe chronic obstructive pulmonary disease were randomized into 3 groups with 15 patients in each group. Group I (LABAâ¯+â¯inhaled corticosteroid) received formoterol/budesonide, group II (LAMAâ¯+â¯inhaled corticosteroid) received tiotropium/budesonide and group III (LABAâ¯+â¯LAMA) received formoterol/tiotropium for 12 weeks. Patients were assessed initially and then at 4 and 12 weeks by measuring the changes that occurred in forced expiratory volume in 1 second as a percent of predicted and in the modified Medical Research Council dyspnea scale. Plasma concentrations of tumor necrosis factor α, fibrinogen, and interleukin 6 were simultaneously measured. RESULTS: The 3 study groups were statistically similar with respect to their demographic data and disease characteristics. All therapeutic options produced an improvement in forced expiratory volume in 1 second as a percent of predicted and in the modified Medical Research Council dyspnea scale as well as a reduction in plasma concentrations of the inflammatory markers. The effects produced by the three therapeutic combinations on forced expiratory volume in 1 second as a percent of predicted, plasma tumor necrosis factor α, interleukin 6, and fibrinogen concentrations were statistically similar after 4 and 12 weeks (4 weeks after treatment: Pâ¯=â¯0.358, Pâ¯=â¯0.284, Pâ¯=â¯0.155, and Pâ¯=â¯0.155, respectively, and 12 weeks after treatment: Pâ¯=â¯0.710, Pâ¯=â¯0.773, Pâ¯=â¯0.240, and Pâ¯=â¯0.076, respectively). CONCLUSIONS: In nonasthmatic patients with moderate to severe chronic obstructive pulmonary disease, the 3 therapeutic combinations showed similar effectiveness. The results of this pilot study also suggest that inflammatory markers can be used to track disease activity. Clinicaltrials.gov identifier: NCT04520230. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).
RESUMEN
PURPOSE: This study aimed to evaluate the role of the extracellular part of insulin-regulated aminopeptidase (IRAPe), interleukin (IL)-34, irisin, and visfatin in the development of insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM). METHODS: This observational parallel-group study was conducted in 60 subjects without T2DM who served as a control group and 60 patients with newly diagnosed T2DM. The 2 groups were matched for age, sex ratio, and body mass index. Anthropometric parameters; fasting blood glucose; fasting plasma insulin; Homeostatic Model Assessment for IR (HOMA-IR) index; glycated hemoglobin (HbA1c); and circulating levels of IL-34, visfatin, irisin, and IRAPe were assessed. RESULTS: The group with T2DM showed significantly higher IL-34 and visfatin levels and significantly lower irisin and IRAPe levels as compared to the healthy control group. IL-34 and visfatin were significantly positively correlated with fasting blood glucose, fasting plasma insulin, HOMA-IR, and HbA1c. On the other hand, irisin and IRAPe were significantly negatively correlated with fasting blood glucose, fasting plasma insulin, HOMA-IR, and HbA1c. IL-34 was positively associated with visfatin, while negatively associated with both irisin and IRAPe. IMPLICATIONS: IL-34, visfatin, irisin, and IRAPe may play a vital role in T2DM and in diabetes-associated IR. Additionally, IRAPe may represent a useful and direct marker for use in the detection of IR in the diabetic population. ClinicalTrials.gov identifier: NCT04107259.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Aminopeptidasas , Glucemia , Humanos , Insulina , InterleucinasRESUMEN
AIM: This study aimed at evaluating the effect of Nigella sativa (NS) on anthropometric, metabolic and inflammatory parameters and examining its related molecular mechanisms in obese prediabetic individuals as compared to both lifestyle modification (LM) and Metformin (Met). METHODS: This study included 117 obese prediabetic subjects who were randomized into LM group which followed controlled diet and exercise regimen, metformin group received metformin 500â¯mg tablets twice daily and NS group received NS oil soft gelatin capsules 450â¯mg twice daily. Anthropometric (weight, BMI), glycemic, lipid, inflammatory parameters and genetic expressions of Sirtuin-1 (SIRT1) and p53 genes were assessed before and six months after interventions. RESULTS: Post-intervention pairwise comparison revealed that, NS was statistically similar to metformin in improving anthropometric, glycemic parameters and SIRT1 gene expression. There was non-significant difference between LM and NS regarding their effects on anthropometric and most of glycemic parameters. Lifestyle modification group showed significantly higher HOMA-B and SIRT1 expression than NS and metformin. Nigella sativa improved lipid panel and significantly reduced TNF-α level and Castelli risk index-I as compared to other interventions. CONCLUSION: Nigella sativa uniquely improved lipid panel and significantly suppressed inflammation. Therefore, Nigella sativa may represent a promising intervention for obese prediabetic subjects. Clinicaltrial.gov ID: NCT03925714.
Asunto(s)
Metformina , Nigella sativa , Obesidad , Preparaciones de Plantas/uso terapéutico , Estado Prediabético , Glucemia , Humanos , Inflamación/tratamiento farmacológico , Estilo de Vida , Metformina/uso terapéutico , Nigella sativa/química , Obesidad/complicaciones , Obesidad/terapia , Estado Prediabético/complicaciones , Estado Prediabético/tratamiento farmacológico , Sirtuina 1RESUMEN
OBJECTIVE: There are discrepancies about the relationship of IL-6, clusterin and irisin with obesity and obesity associated insulin resistance and also about their sexual dimorphism. This study aimed at evaluating the circulating levels of IL-6, clusterin and irisin in obese subjects of both sexes who had different grades of obesity and examining their sexual dimorphism and their association with insulin resistance. METHODS: This study included 176 non-diabetic subjects of both sexes who were classified according to their sex into two groups; the male and the female groups. The male group (88 men) was classified according to BMI into; group 1 (22 lean men), group 2 (22 class I obese men), group 3 (22 class II obese men) and group 4 (22 class III obese men). The female group (88 women) was classified according to BMI exactly as the male group. Metabolic parameters, IL-6, clusterin, and irisin levels were measured. Data were analyzed by ANOVA test, post hoc Tukey's test and independent t-test. Pearson correlation was used to assess the association between variables. RESULTS: In obese subjects of both sexes, circulating IL-6, clusterin and irisin levels were significantly elevated and positively correlated with HOMA-IR. Obese males showed significantly higher HOMA-IR, IL-6, clusterin and irisin levels than obese females. CONCLUSION: Obesity in both sexes, especially in males was associated with high levels of IL-6, clusterin and irisin and worsened the metabolic pattern. Circulating IL-6, clusterin and irisin may represent possible therapeutic targets for insulin resistance in obese subjects.
Asunto(s)
Clusterina/sangre , Fibronectinas/sangre , Resistencia a la Insulina , Interleucina-6 , Obesidad/sangre , Caracteres Sexuales , Índice de Masa Corporal , Femenino , Humanos , Interleucina-6/sangre , Masculino , Obesidad/clasificaciónRESUMEN
ABSTRACT Objective: There are discrepancies about the relationship of IL-6, clusterin and irisin with obesity and obesity associated insulin resistance and also about their sexual dimorphism. This study aimed at evaluating the circulating levels of IL-6, clusterin and irisin in obese subjects of both sexes who had different grades of obesity and examining their sexual dimorphism and their association with insulin resistance. Subjects and methods: This study included 176 non-diabetic subjects of both sexes who were classified according to their sex into two groups; the male and the female groups. The male group (88 men) was classified according to BMI into; group 1 (22 lean men), group 2 (22 class I obese men), group 3 (22 class II obese men) and group 4 (22 class III obese men). The female group (88 women) was classified according to BMI exactly as the male group. Metabolic parameters, IL-6, clusterin, and irisin levels were measured. Data were analyzed by ANOVA test, post hoc Tukey's test and independent t-test. Pearson correlation was used to assess the association between variables. Results: In obese subjects of both sexes, circulating IL-6, clusterin and irisin levels were significantly elevated and positively correlated with HOMA-IR. Obese males showed significantly higher HOMA-IR, IL-6, clusterin and irisin levels than obese females. Conclusion: Obesity in both sexes, especially in males was associated with high levels of IL-6, clusterin and irisin and worsened the metabolic pattern. Circulating IL-6, clusterin and irisin may represent possible therapeutic targets for insulin resistance in obese subjects.
Asunto(s)
Humanos , Masculino , Femenino , Resistencia a la Insulina , Fibronectinas/sangre , Interleucina-6/sangre , Caracteres Sexuales , Clusterina/sangre , Obesidad/sangre , Índice de Masa Corporal , Obesidad/clasificaciónRESUMEN
BACKGROUND/PURPOSE: Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver cirrhosis. HE is associated with poor survival and detrimental effects on quality of life (QOL). The drawbacks of the long-term use of rifaximin in HE necessitates searching for alternative therapies. In this context, our study aimed at evaluating the safety and efficacy of nitazoxanide (NTZ) as compared to rifaximin (RFX) in preventing the recurrence of HE and assessing its impact on QOL. PATIENTS AND METHODS: This prospective, randomized, double-blind controlled study included 60 patients who were randomly assigned to receive either rifaximin 550 mg twice daily (group 1; n = 30) or nitazoxanide 500 mg twice daily (group 2; n = 30) for 24 weeks. During the study period, the patients' neurological symptoms, mental status, and performance were monitored. The serum levels of HE triggers (ammonia, TNF-α, and octopamine) were assessed. The patients' health-related quality of life was also evaluated. RESULTS: Six months after treatment, patients on NTZ therapy showed a statistically significant improvement in CHESS score and mental status. NTZ provided 136 days of remission vs 67 days of remission for patients on RFX (P1 = .0001) and significant reduction in Child score (P1 = .018). Additionally, NTZ showed a statistically significant decrease in serum ammonia, TNF-α, and octopamine levels as compared to rifaximin. Regarding QOL, NTZ group showed an improvement in total Chronic Liver Disease Questionnaire (CLDQ) score. Both groups experienced minor controllable side effects. CONCLUSION: Nitazoxanide may represent a suitable and safe alternative therapy to rifaximin in preventing the recurrence of hepatic encephalopathy.
Asunto(s)
Encefalopatía Hepática , Rifamicinas , Niño , Encefalopatía Hepática/tratamiento farmacológico , Encefalopatía Hepática/etiología , Encefalopatía Hepática/prevención & control , Humanos , Cirrosis Hepática , Nitrocompuestos , Estudios Prospectivos , Calidad de Vida , Rifaximina , TiazolesRESUMEN
Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Tramadol/farmacología , Analgésicos Opioides/farmacología , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antidepresivos/farmacología , Antioxidantes/farmacología , COVID-19/complicaciones , COVID-19/fisiopatología , Reposicionamiento de Medicamentos , Humanos , Factores Inmunológicos/farmacología , Modelos Biológicos , Pandemias , SARS-CoV-2RESUMEN
Background: Elevated homocysteine levels and malnutrition are frequently detected in hemodialysis patients and are believed to exacerbate cardiovascular comorbidities. Omega-3 fatty acids have been postulated to lower homocysteine levels by up-regulating metabolic enzymes and improving substrate availability for homocysteine degradation. Additionally, it has been suggested that prevention of folate depletion by vitamin E consumption decreases homocysteine levels. However, data on the effect of omega-3 fatty acids and/or vitamin E on homocysteine levels and nutritional status have been inconclusive. Therefore, this study was planned to examine the effect of combined supplementation of fish oil, as a source of omega-3 fatty acids, with wheat germ oil, as a source of vitamin E, on homocysteine and nutritional indices in hemodialysis patients. Methods: This study was a randomized, double-blind, placebo-controlled trial. Forty-six hemodialysis patients were randomly assigned to two equally-sized groups; a supplemented group who received 3000 mg/day of fish oil [1053 mg omega-3 fatty acids] plus 300 mg/day of wheat germ oil [0.765 mg vitamin E], and a matched placebo group who received placebo capsules for 4 months. Serum homocysteine and different nutritional indices were measured before and after the intervention. Results: Twenty patients in each group completed the study. At the end of the study, there were no significant changes in homocysteine levels and in the nutritional indices neither in the supplemented nor in the placebo-control groups (p > 0.05). Conclusions: Fish oil and wheat germ oil combination did not produce significant effects on serum homocysteine levels and nutritional indices of hemodialysis patients.
Asunto(s)
Ácidos Grasos Omega-3 , Aceites de Pescado , Suplementos Dietéticos , Método Doble Ciego , Homocisteína , Humanos , Evaluación Nutricional , Aceites de Plantas , Diálisis RenalRESUMEN
PURPOSE: This study aimed to examine the impact of combined supplementation of fish oil (FO) with antioxidants like wheat germ oil (WGO) on mineral-bone and inflammatory markers in maintenance HD patients. METHODS: This randomized, double-blind, placebo-controlled trial involved 46 HD patients who were randomly assigned into two groups to receive daily 3000 mg of FO [1053 mg omega-3 fatty acids (ω-3 FAs)] plus 300 mg of WGO [0.765 mg vitamin E] or placebo for 4 months. Blood concentrations of hemoglobin (Hgb), white blood cells, mineral-bone parameters including serum calcium (Ca), phosphorus, calcium-phosphorus product, parathyroid hormone, alkaline phosphatase, and osteoprotegerin and serum concentrations of inflammatory markers including high-sensitivity C-reactive protein, ferritin, and uric acid were measured before and after the intervention. RESULTS: Eighty-seven percentage of patients in each group completed the study. The mean serum Ca levels increased significantly in the supplemented group at the end of study (p = 0.0016), and this increment was also significant as compared to placebo group (p = 0.0418). No significant alterations were observed in the other measured parameters within each group during the study (as p values were >0.05). CONCLUSION: FO plus WGO supplementation showed beneficial effect on serum Ca levels of HD patients without any statistically significant effect on other mineral-bone and inflammatory markers. Further investigations are required to confirm it.
Asunto(s)
Aceites de Pescado/uso terapéutico , Fallo Renal Crónico/sangre , Fallo Renal Crónico/tratamiento farmacológico , Aceites de Plantas/uso terapéutico , Adulto , Fosfatasa Alcalina/sangre , Antioxidantes/uso terapéutico , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Calcio/sangre , Suplementos Dietéticos , Método Doble Ciego , Quimioterapia Combinada , Ácidos Grasos Omega-3/uso terapéutico , Femenino , Ferritinas/sangre , Hemoglobinas/metabolismo , Humanos , Fallo Renal Crónico/terapia , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Osteoprotegerina/sangre , Hormona Paratiroidea/sangre , Fósforo/sangre , Estudios Prospectivos , Diálisis Renal , Ácido Úrico/sangreRESUMEN
This study aimed to evaluate the associated cardiovascular risk in Egyptian healthy consumers of different types of combined oral contraceptives pills (COCPs) via determination of lipids profiles, Castelli index I, leptin, adiponectin, and resistin concentrations as cardiovascular risk factors. In this cross-sectional study, the study groups consisted of control group that represented by 30 healthy married women who were not on any contraceptive mean or any hormonal therapy and had normal menstrual cycles, group two consisted of 30 women who were users of Levonorgesterl 0.15 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, group three consisted of 30 women who were users of Gestodene 0.075 mg plus Ethinylestradiol 0.03 mg as 21 days cycle, and group four consisted of 30 women who were users of Drospirenone 3 mg plus Ethinylestradiol 0.03 mg as 21 days cycle. One-way analysis of variance followed by LSD post hoc test was used for comparison of variables. P value <0.05 was considered to be significant. The comparison of the studied groups revealed that COCPs containing levonorgestrel plus ethinylestradiol resulted in significantly lower adiponectin level, and significantly higher leptin and resistin levels with more atherogenic lipid profile presented by significantly higher LDL-C, significantly lower HDL-C concentrations, and significantly higher atherogenic index. Formulation containing ethinylestradiol combined with gestodene neither altered adipose tissue function nor showed deleterious effect on lipid panel. Formulation containing ethinylestradiol combined with drospirenone resulted in significantly higher HDL-C and adiponectin concentrations. In conclusion, the uptake of COCPs containing levonorgestrel plus ethinylestradiol is associated with high cardiovascular risk since this formulation showed significantly lower adiponectin concentration, significantly higher leptin, resistin, and atherogenic index as compared to other studied groups. By contrast, the formulations containing ethinylestradiol combined with third generation progestin gestodene or fourth generation progestin drospirenone are associated with low cardiovascular risk since they neither altered adipose tissue function nor impaired lipoprotein metabolism as experienced by their favorable effect on leptin, adiponectin, and resistin, with non-changed atherogenic index, higher HDL-C levels and lower LDL-C levels as compared to levonorgestrel plus ethinylestradiol formulation.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Anticonceptivos Orales Combinados/efectos adversos , Adiponectina/sangre , Tejido Adiposo/efectos de los fármacos , Adulto , Androstenos , Antropometría , Química Farmacéutica , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Combinación de Medicamentos , Egipto/epidemiología , Etinilestradiol , Femenino , Humanos , Leptina/sangre , Levonorgestrel , Norpregnenos , Resistina/sangre , Factores de RiesgoRESUMEN
BACKGROUND: Oxidative stress plays an important role in the development of diabetic cardiomyopathy. Alpha-lipoic acid (ALA) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction. AIM: We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular (LV) dysfunction in children and adolescents with asymptomatic type 1 diabetes (T1D). SUBJECTS AND METHODS: Thirty T1D patients (aged 10-14) were randomized to receive insulin treatment (n = 15) or insulin plus alpha-lipoic acid 300 mg twice daily (n = 15) for four months. Age and sex matched healthy controls (n = 15) were also included. Patients were evaluated with conventional 2-dimensional echocardiographic examination (2D), pulsed tissue Doppler (PTD), and 2-dimensional longitudinal strain echocardiography (2DS) before and after therapy. Glutathione, malondialdhyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), Fas ligand (Fas-L), matrix metalloproteinase 2 (MMP-2), and troponin-I were determined and correlated to echocardiographic parameters. RESULTS: Diabetic patients had significantly lower levels of glutathione and significantly higher MDA, NO, TNF-alpha, Fas-L, MMP-2, and troponin-I levels than control subjects. The expression of transforming growth factor beta (TGF-beta) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients. Significant correlations of mitral e'/a' ratio and left ventricular global peak systolic strain with glutathione, MDA, NO, TNF-alpha, and Fas-L were observed in diabetic patients. Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA, NO, TNF-alpha, Fas-L, MMP-2, troponin-I levels, and TGF-beta gene expression. Moreover, alpha-lipoic acid significantly increased mitral e'/a' ratio and left ventricular global peak systolic strain in diabetic patients. CONCLUSION: These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Cardiomiopatías Diabéticas/tratamiento farmacológico , Ácido Tióctico/administración & dosificación , Disfunción Ventricular Izquierda/tratamiento farmacológico , Adolescente , Antioxidantes/administración & dosificación , Niño , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/metabolismo , Femenino , Humanos , Masculino , Estrés Oxidativo/efectos de los fármacos , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/genética , Disfunción Ventricular Izquierda/metabolismoRESUMEN
INTRODUCTION: Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and resources. This study investigates the role of alpha-lipoic acid (ALA) in end stage renal disease patients undergoing hemodialysis. By the virtue of its antioxidative effects, ALA is expected to act as an erythropoietin (EPO) adjuvant, and also has extended beneficial effects on endothelial dysfunction. METHODS: Forty-four patients undergoing hemodialysis and receiving EPO were randomized into two groups: the first group received ALA 600 mg once daily for 3 months; while the other group represented the control group. Parameters measured at baseline and at end of study were hemoglobin, EPO doses, EPO resistance index (ERI), iron store indices, malondialdehyde, oxidized low-density lipoprotein (ox-LDL), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA), as well as routine laboratory follow-up. RESULTS: EPO doses and ERI were significantly decreased in the treatment group, while they did not change in the control group. Hemoglobin, iron store indices, malondialdehyde, oxidized ox-LDL, IL-6, TNF-α, and ADMA were similar in both treatment and control groups at baseline, and did not change by the end of study period. Likewise, routine laboratory measures were not affected by the treatment. CONCLUSION: ALA could be used in hemodialysis patients to reduce requirements for EPO. However, larger and longer term studies are required to clarify the exact role of ALA in hemodialysis as well as in pre-hemodialysis patients.