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Background: ß-thalassemia major is microcytic hypochromic anemia disorder inherited from parents, resulting from a mutation in the ß-globin locus. As a result, a quantitative defective hemoglobin synthesis and relative excess in α-globin is occurred. As such, frequent blood transfusion is required, that leads to iron overload. Iron overload results in several pathological complications, including cell death, tissue injury, organ dysfunction, and liver fibrosis. The present study examined the effectiveness of nigella Sativa and manuka honey combination or manuka honey alone to the conventional therapy (Deferasirox + blood transfusion) used for preventing and managing iron overload in pediatric ß-thalassemia major patients. Methods: One hundred sixty-five patients participated in this randomized, double-blind, standard therapy-controlled, parallel-design multisite trial. The patients were randomly allocated into three groups, receiving either 500 mg nigella sativa oil combined with manuka honey lozenge (344 mg) daily or manuka honey alone plus the conventional therapy for ten treatment months. Ferritin level, serum iron, transferrin saturation, total iron binding capacity, alanine transaminase, and aspartate transaminase were determined at baseline and month 10. Results: Eventually, serum ferritin and iron were decreased significantly in the nigella sativa + manuka honey group as compared with the control group. Other clinical parameters were significantly impacted. The level of alanine transaminase and aspartate transaminase were significantly decreased in the nigella sativa plus manuka honey group compared with the control group. Conclusion: Results showed that nigella sativa plus manuka honey was more effective than manuka alone or the conventional treatment alone in managing iron overload of ß-thalassemia major patients.
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Introduction: Adherence studies among rheumatoid arthritis (RA) patients, in Egypt and throughout the Middle East region, are lacking. This study aimed to evaluate methotrexate (MTX) adherence in Rheumatoid arthritis (RA) patients and to identify specific non-adherence predictors. Methods: A cross-sectional observational study included 300 RA patients who were administered MTX for at least one year. The survey was completed through direct interviews. The demographic patient data were collected (age, education, sex, work status, disease duration, duration of MTX administration and current dose). Patients' adherence to MTX predictors for non-adherence, MTX side effects and functional disability were assessed in the study. Results: Majority of respondents showed good MTX adherence, and more than 50% of patient's experienced MTX side effects. A large percentage of participants showed low knowledge about MTX nature and side effects. Most participants reported no or some difficulty in quality of life-related activities and functional disability. Conclusion: MTX adherence and awareness were positively correlated to many variables, including, age, educational level and disease duration, which in turn has its positive impact on the patient's quality of life. Still, more research is needed to determine the impact of non-adherence on the patient's health outcomes.
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BACKGROUND: Multimodality is required for the treatment of breast cancer. Surgery, radiation (RT), and systemic therapy were traditionally used. Pharmacotherapy includes different drug mechanisms, such as chemotherapy, hormone therapy, and targeted therapies, alone or in combination with radiotherapy. While radiation offers numerous benefits, it also has certain harmful risks. such as cardiac and pulmonary toxicity, lymphedema, and secondary cancer. Modern radiation techniques have been developed to reduce organs at risk (OAR) doses. MATERIALS AND METHODS: This study is a prospective feasibility trial conducted at the Fayium Oncology Center on patients with left breast cancer receiving adjuvant locoregional radiotherapy after either breast conservative surgery (BCS) or modified radical mastectomy (MRM). This study aimed to assess the proportion of patients who are fit both physically and intellectually to undergo breast radiotherapy using the deep inspiratory breath-holding (DIBH) technique, comparing different dosimetric outcomes between the 3D dimensional conformal with DIBH and 4D-CT IMRT plans of the same patient. RESULTS: D95 of the clinical target volume (CTV) of the target is significantly higher in the 3D DIBH plan than in the IMRT plan, with an average of 90.812% vs. 86.944%. The dosimetry of the mean heart dose (MHD) in the 4D-CT IMRT plan was significantly lower than in the 3D conformal with the DIBH plan (2.6224 vs. 4.056 Gy, p < 0.0064), and no significant difference between the two plans regarding mean left anterior descending artery (LAD) (14.696 vs. 13.492 Gy, p < 0.58), maximum LAD (39.9 vs. 43.5 Gy, p < 0.35), and V20 of the ipsilateral lung (18.66% vs. 16.306%, p < 0.88) was observed. Internal mammary chain (IMC) irradiation was better in the 4D-CT IMRT plan. CONCLUSIONS: Radiotherapy of the breast and chest wall with the 4D-CT IMRT technique appears not to be inferior to the 3D conformal with the DIBH technique and can be used as an alternative to the 3D conformal with the DIBH technique in patients meeting the exclusion criteria for performing the DIBH maneuver concerning coverage to target volumes or unacceptably high doses to OAR.
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(1) Background: During 2019, the COVID-19 pandemic was threatening healthcare services and workers, and acquiring immunity was an option to stop or limit the burden of this pandemic. Herd immunity was a top priority worldwide as the virus was spreading rapidly. It was estimated that 67% of the total global population should be immunized against COVID-19 to achieve herd immunity. The aim of the current study is to investigate different perceptions of healthcare workers in the Kingdom of Bahrain and Egypt using an online survey in an attempt to evaluate their awareness and concerns regarding new variants and booster doses. (2) Methods: This study conducted a survey on healthcare workers in the Kingdom of Bahrain and Egypt about their perception and concerns on the COVID-19 vaccines. (3) Results: The study found that out of 389 healthcare workers 46.1% of the physicians were not willing to take the booster doses (p = 0.004). Physicians also did not support taking the COVID-19 vaccine as an annual vaccine (p = 0.04). Furthermore, to assess the association between the type of vaccine taken with the willingness of taking a booster vaccine, healthcare workers beliefs on vaccine effectiveness (p = 0.001), suspension or contact with patients (p = 0.000), and infection after COVID-19 vaccination (p = 0.016) were significant. (4) Conclusion: Knowledge about vaccine accreditation and regulation should be dispersed more widely to ensure that the population has a positive perception on vaccine safety and effectiveness.
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Objectives: The current study aims to assess the efficacy and safety of Enoxaparin and hydroxychloroquine (HCQ) used as monothrapy or polytherapy versus standard care alone in Coronavirus 2019 (COVID-19) infected patients. Methods: The current study included two hundred patients with laboratory confirmed COVID-19 infection. Patients admitted to hospital were randomly allocated into four groups: group I: received standard COVID-19 therapy, group II: received Enoxaparin 40mg/day subcutaneously (SC) plus standard therapy, group III: received 400 mg/day HCQ plus standard therapy & group IV: received a combination of 400 mg/day HCQ and Enoxaparin plus standard COVID-19 therapy. The disease progression was evaluated by duration to a negative polymerase chain reaction (PCR), length of hospital or Intensive Care Unit (ICU) stay, and mortality rate. The safety of treatments was evaluated by measuring adverse effects. Results: The length of hospital stay, ICU admission and mortality were significantly decreased in Enoxaparin plus standard COVID-19 therapy group versus other groups. Conclusion: These findings suggest that Enoxaparin was safe, effective, and well tolerated and has a role in decreasing the progression of the disease and its complications while HCQ did not discover any evidence of extra therapeutic benefits.
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BACKGROUND: The outbreak has harmed patients with multiple comorbidities and chronic conditions. The pandemic's psychological impact is thought to change their routine of seeking medical care. Research Question or Hypothesis: During COVID-19, patients with chronic conditions may experience anxiety, depression, and stress, and their pattern of seeking medical care may change. MATERIALS AND METHODS: In May 2021, a cross-sectional, web-based study of patients with chronic diseases was conducted. Eligible patients (1036) were assessed for psychological disorders, primarily depression, stress, and anxiety, using the DASS-21 scale, and their pattern of receiving medical care during COVID-19. RESULTS: During the pandemic, 52.5% of the patients with chronic diseases were depressed, 57.9% were anxious, and 35.6% were stressed. Patients with chronic diseases who had moderate to severe depression (34.9% versus 45.1%, p = 0.001), moderate to severe anxiety (43.6% versus 53.8%, p = 0.001), or moderate to severe stress (14.9% versus 34.8%, p = 0.001) were significantly more likely to have no follow-up for their chronic conditions. CONCLUSIONS: Patients with chronic conditions experienced significant anxiety, depression, and stress during COVID-19, which changed their pattern of seeking medical care, and the majority of them did not receive follow-up for their chronic conditions.
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There seem to currently be no therapeutic medications found for the severe coronavirus infection in 2019 (COVID-19). In light of this, it has been hypothesized that the immunomodulatory treatment known as tocilizumab can lessen the inflammatory response that occurs in the respiratory system, speed up the process of clinical benefit, lower the risk of death, and avert the need for ventilators. This randomized controlled trial (RCT) studied patients with a proven infection of SARS-CoV-2 and hyperinflammatory reactions. The inclusion criteria included fever (body temperature > 38 °C), pulmonary infiltrates, or supplemental oxygen. The patients received either conventional treatment with one dose of either tocilizumab (8 mg per kilogram of body weight) or conventional treatment only. The subjects were randomized to receive either treatment with a 1:1 ratio. A time-to-event test was conducted to determine the time to intubation or death. There was an insignificant difference between the investigated groups regarding the time to death, time to mechanical ventilation, and percentage of deaths. The conventional group's median (IQR) hospital length of stay was 4 (3-6) days, whereas the tocilizumab therapy group was 7 (4.75-10) days. There was a substantial difference in the mechanical ventilation rates in both groups, which were 17 (34%) and 28 (56%), respectively. In hospitalized patients with severe illness and COVID-19, tocilizumab was ineffective in preventing intubation or death. Trials must be larger, however, in order to exclude the potential benefits or harms.
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The aim of this study was to compare the effect of a single high-dose rosuvastatin versus atorvastatin preloading in ST-elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI.) Methods: A total of 99 patients presented with STEMI and were randomly divided into three groupsa control group (n = 33) with no statin treatment, an atorvastatin group (n = 33) with a single 80 mg atorvastatin dose and the rosuvastatin group (n = 33) with a single 40 mg rosuvastatin dose in the emergency room (ER) prior to PCI. Post-interventional thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) were recorded, and ST-segment resolution was measured. Results: CTFC was significantly lower for the atorvastatin group (p-value < 0.01) than in the control group. A final TIMI flow grade 3 was achieved in 32 (97.0%) patients in the rosuvastatin group and 28 (84.8%) patients in the atorvastatin group compared with only 25 (75.8%) patients in the control group (p = 0.014). Peak CK-MB in the rosuvastatin group (263.2 [207.2−315.6]) and the atorvastatin group (208 [151.0−314.1]) was lower compared to that in the control group (398.4 [303.9−459.3]); p < 0.001. Conclusions: A single extensive dose of lipophilic atorvastatin prior to primary PCI in STEMI patients showed better improvement in microvascular myocardial perfusion compared to hydrophilic rosuvastatin.
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BACKGROUND: Breast cancer is a highly heterogeneous type of neoplasia with molecular and biochemical alterations in the ductal epithelium. AnxA2 has a diverse functions and through intracellular interaction with other molecules promotes carcinogenesis. AIMS: To study the possible involvement of AnxA2 in breast cancer heterogeneity and cancer progression. PATIENTS AND METHODS: Tumor tissue and serum were obtained from different breast cancer subtypes. Tumor tissues were processed for histopathological studies. AnxA2 levels were assessed in the tissues by H scoring and in the serum by ELISA. AnxA2 levels were correlated with HER2 and Ki67 and with clinicopathological data. Normal breast tissues and serum from healthy subjects were used as controls. RESULTS: AnxA2 showed a peculiar distribution in tumor tissues and nearby interstitial tissues. Pattern of expressions varied in different subtypes with the highest expression in triple negative subtype. Tissue and serum AnxA2 showed significant co-upregulations in breast cancer. Moreover, they showed positive correlations with HER2 and Ki67 and associations with clinicopathological data including cancer staging and lymph node metastasis. CONCLUSION: For the best of our knowledge this is the first study showing correlation between AnxA2, the proposed prognostic marker and the well-established tumor markers; HER2 and Ki67. AnxA2 might contribute to breast cancer heterogeneity and is associated with poor prognosis. AnxA2 might be a prognostic marker and an additional marker for breast cancer grading and clinical staging. Interestingly, tissue and serum AnxA2 showed a strong correlation. Thus, assessing serum AnxA2 can be a noninvasive prognostic tool.
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Anexina A2 , Neoplasias da Mama , Anexina A2/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Estadiamento de NeoplasiasRESUMO
Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The ß2-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of -31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity.
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Asma , Terbutalina , Animais , Asma/tratamento farmacológico , Broncodilatadores , Criança , Humanos , Pulmão , Tamanho da Partícula , Ratos , Terbutalina/uso terapêuticoRESUMO
Recently, several clinical trials have attempted to find evidence that supports the anticancer use of metformin in breast cancer (BC) patients. The current study evaluates the anticancer activity of metformin in addition to neoadjuvant chemotherapy (NACT) in locally advanced BC patients. Additionally, we assess the safety and tolerability of this combination and its effect on the quality of life (QoL) of BC patients. Eighty non-diabetic female patients with proven locally advanced BC were randomized into two arms. The first arm received anthracycline/taxane-based NACT plus metformin. The second arm received anthracycline/taxane-based NACT only. Overall response rate (ORR), clinical complete response (cCr), pathological complete response (pCR), and breast conservative rate (BCR) were evaluated between both groups, and correlated with serum metformin concentration. ORR, cCr, pCR, and BCR increased non-significantly in the metformin group compared to the control group; 80.6% vs 68.4%, 27.8% vs 10.5%, 22.2% vs 10.5%, and 19.4% vs 13.2%, respectively. A trend towards cCR and pCR was associated with higher serum metformin concentrations. Metformin decreased the incidence of peripheral neuropathy, bone pain, and arthralgia, although worsened the gastrointestinal adverse events. Metformin combination with NACT has no effect on the QoL of BC patients. Metformin combination with NACT is safe, tolerable, and improves non-significantly the clinical and pathological tumor response of BC patients.
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Neoplasias da Mama , Metformina , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Metformina/uso terapêutico , Terapia Neoadjuvante , Qualidade de Vida , Taxoides/uso terapêuticoRESUMO
BACKGROUND: Asthma is a significant public health issue that poses a substantial health and economic burden. Despite the availability of effective asthma medications, its management remain suboptimal. Recent asthma guidelines have highlighted the importance of pharmacist unique position and its interventional strategies in positively impacting asthma treatment outcomes. Therefore, this study aimed to assess the degree of Egyptian pharmacists' knowledge, attitudes, as well as their practices towards asthma management in line with the recent asthma guidelines. METHODS: This cross-sectional study was conducted among 800 pharmacists working in different private and governmental sectors. The data were collected using a 37-item pre-validated self-administered KAP questionnaire. The data were analyzed using Student's t-test and analysis of variance to assess the association between each KAP level and the sociodemographic variables at the significance level of 0.05. RESULTS: Of the 800 distributed questionnaire, a total of 550 participants (316 Male, and 234 Female) responded, representing a 68.7% response rate. The mean ± SD score of knowledge, attitude, practice, and barrier was 5.49 ± 1.65 (min = 0; max = 8), 23.5 ± 2.84 (min = 15, max = 30), 43.12 ± 8.61 (min = 28, max = 62), and 27.76 ± 3.72 (min = 17, max = 39), respectively. The results showed that poor knowledge, attitude, and practice scores were achieved by 30.54, 0, and 38.72% of participants, respectively. CONCLUSION: Our findings revealed the inconsistencies between poor pharmacists' knowledge and practices with respect to their positive attitudes. The lack of pharmacists' knowledge and compliance to recent GINA guidelines in this study highlight the crucial need for effective Educational strategies that should better equip pharmacists for their potential role in asthma care.
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Background: Continuous Positive Airway Pressure (CPAP), BiPhasic Positive Airway Pressure (BiPAP), and high flow nasal cannula (HFNC) show some evidence to have efficacy in COVID-19 patients. Delivery during noninvasive mechanical ventilation (NIV) or HFNC gives faster and more enhanced clinical effects than when aerosols are given without assisted breath. The present work aimed to compare the effect of BiPhasic Positive Airway Pressure (BiPAP) mode at two different pressures; low BiPAP (Inspiratory Positive Airway Pressure (IPAP)/Expiratory Positive Airway Pressure (EPAP) of 10/5 cm water) and high BiPAP (IPAP/EPAP of 20/5 cm water), with HFNC system on pulmonary and systemic drug delivery of salbutamol. On the first day of the experiment, all patients received 2500 µg salbutamol using Aerogen Solo vibrating mesh nebulizer. Urine samples 30 min post-dose and cumulative urinary salbutamol during the next 24 h were collected on the next day. On the third day, the ex-vivo filter was inserted before the patient to collect the delivered dose to the patient of the 2500 µg salbutamol. Salbutamol was quantified using high-performance liquid chromatography (HPLC). Results: Low-pressure BiPAP showed the highest amount delivered to the lung after 30 min followed by HFNC then high-pressure BiPAP. But the significant difference was only observed between low and high-pressure BiPAP modes (p = 0.012). Low-pressure BiPAP showed the highest delivered systemic delivery amount followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.017) and high-pressure BiPAP (p = 0.008). No significant difference was reported between HFNC and high-pressure BiPAP. The ex-vivo filter was the greatest in the case of low-pressure BiPAP followed by HFNC then high-pressure BiPAP. Low-pressure BiPAP was significantly higher than HFNC (p = 0.033) and high-pressure BiPAP (p = 0.008). Also, no significant difference was found between HFNC and high-pressure BiPAP. Conclusions: Our results of pulmonary, systemic, and ex-vivo drug delivery were found to be consistent. The low BiPAP delivered the highest amount followed by the HFNC then the high BiPAP with the least amount. However, no significant difference was found between HFNC and high BiPAP.
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INTRODUCTION: Several clinical trials have attempted to find evidence that supports the use of metformin as an anticancer treatment. However, the observed effects on various breast cancer (BC) outcomes have been heterogeneous. AREAS COVERED: Based on the outcomes of previous clinical trials, this review discusses the patients' characteristics, cancer intrinsic subtypes, cancer stage, and anticancer treatments that may influence the anticancer effect of metformin on BC outcomes. Additionally, the safety and tolerability of metformin addition to various anticancer regimens are reviewed. EXPERT OPINION: Metformin is a challenging anticancer agent in BC cohorts, besides being safe and well-tolerated at antidiabetic doses. Survival benefits of metformin have been observed in BC patients with: hormone receptor-positive, human epidermal growth factor receptor-2 overexpression, and high insulin like growth factor-1 receptor expression on the tumor surface. Moreover, patients with diabetes receiving metformin experienced better survival outcomes compared to diabetic patients not receiving metformin. Additionally, metformin has anti-proliferative activity in patients with BC who have high insulin resistance and high body mass index. Besides, metformin has been shown to decrease metastatic events, and enhance the level of metabolic- and insulin-related biomarkers associated with carcinogenesis. Finally, most adverse events following metformin treatment were low-grade GIT toxicities.
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Neoplasias da Mama , Metformina , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/uso terapêutico , Metformina/efeitos adversosRESUMO
BACKGROUND: Awareness about the COVID-19 vaccine's adverse effects is crucial for gaining public trust. As we still lack proof of vaccines' safety, this survey aimed to investigate Egyptians' general awareness of the Sinopharm and AstraZeneca vaccines against COVID-19 and provide considerable evidence on their side effects and complications. METHODS: A cross-sectional questionnaire-based study was conducted in Egypt between 20 September and 10 October in 2021, with multiple-choice questions (MCQs) covering all data on vaccine administration confusion, adverse effects or intensity, and complications. RESULTS: Among the 390 participants, 42.3% reported being hesitant before receiving one of the vaccines. About 40.3% of participants were previously infected before getting vaccinated while only 4.6% reported being infected after vaccination. The AstraZeneca vaccine demonstrated higher side effects and symptoms than the Sinopharm vaccine while the Sinopharm vaccine showed a significantly higher rate of COVID-19 infection after vaccination. CONCLUSIONS: People with higher educational levels and chronic respiratory diseases represent an excellent model for accepting COVID-19 vaccination. A booster shot is recommended for people vaccinated with the Sinopharm vaccine due to a significantly higher rate of COVID-19 infection after vaccination; however, the Sinopharm vaccine shows a more acceptable safety profile.
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OBJECTIVES: In recent clinical studies, saxagliptin exhibited nephroprotective potential by lowering albuminuria. In this study, we aimed to determine whether these kidney effects of saxagliptin were mediated by changes in markers of kidney tubular damage, including urinary neutrophil gelatinase-associated protein (uNGAL) and liver-type fatty acid-binding protein (uL-FABP). METHODS: Our study included 80 patients with type 2 diabetes, hypertension and mild to moderate diabetic kidney disease (DKD) with prevalent albuminuria. Patients were either randomly assigned to saxagliptin as add-on therapy or remained unchanged on their stable antidiabetic therapy as a control arm. RESULTS: Saxagliptin significantly reduced uNGAL with a median change of -25.4% (interquartile range [IQR], -35.6% to -12.2%) compared with the control group (median change, -0.91%; IQR, -12% to 11.88%; p<0.001) after 3 months. Similarly, patients given saxagliptin had a highly significant reduction in uL-FABP (median change, -24.4%; IQR, -30.5% to -15.1%) compared with controls (median change, -3.8%; IQR -10% to 12.5%; p<0.001). Median estimated glomerular filtration rate (eGFR) values after 3 months in the saxagliptin arm were significantly higher (76.5 mL/min per 1.73 m2; IQR, 70 to 92.75 mL/min per 1.73 m2) in the low-risk uNGAL group compared with controls (59.8 mL/min per 1.73 m2; IQR, 51 to 76.2 mL/min per 1.73 m2; p=0.002). Also, higher-although not significantly-posttreatment eGFR levels were observed in patients with low risk of uL-FABP (73 mL/min per 1.73 m2; IQR, 58 to 91.3 mL/min per 1.73 m2) compared with controls (57.3 mL/min per 1.73 m2; IQR, 49.5 to 72.6 mL/min per 1.73 m2; p=0.06). No significant increase was observed in high-risk patients for either marker when compared with controls. CONCLUSIONS: The albuminuria-lowering effect of saxagliptin may be due to inhibition of kidney tubular damage. Use of tubular markers may be a promising approach to identifying kidney responders to gliptins.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Adamantano/análogos & derivados , Adulto , Albuminúria , Biomarcadores , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Dipeptídeos , Taxa de Filtração Glomerular , Humanos , RimRESUMO
Nanomedicine has emerged as an important approach for targeting RA medication. Rheumatoid arthritis (RA) is a widespread autoimmune disorder marked by multiple inflamed joints. Gold nanoparticles (GNPs) have been demonstrated as efficacious nanocarriers due to their unique characteristics and the relative simplicity of their synthesis in varied sizes; moreover, they have the capability to alleviate several inflammatory markers. The current objective was to combine methotrexate (MTX) with GNPs to overcome MTX restrictions. GNPs were fabricated by a chemical reduction technique, utilizing sodium citrate and tween 20. The MTX-GNPs formulations were characterized in vitro by % entrapment efficiency (%EE), particle size, polydispersity index (PDI) zeta potential, and % release. The MTX-GNPs formulation was administrated as an intra-articular solution, and additionally, incorporated into a Carbopol gel to investigate its anti-arthritic effectiveness and bioavailability in vivo. The results indicated that a %EE of 87.53 ± 1.10%, and a particle size of 60.62 ± 2.41 nm with a PDI of 0.31 ± 0.03, and a zeta potential of −27.80 ± 0.36 mV were optimal. The in vitro release of MTX from the MTX-GNPs formulation demonstrated that the MTX-GNPs formulation's release was 34.91 ± 1.96% and considerably (p < 0.05) lower than that of free MTX, showing a significant difference in dissolution patterns (p < 0.05). In vivo, MTX-GNPs formulations inhibited IL-6 by 36.52%, ACCP (63.25 %), COMP (28.16%), and RANKL (63.67%), as well as elevated IL-10 by 190.18%. Transdermal MTX-GNPs decreased IL-6 by 22.52%, ACCP (56.63%), COMP (52.64%), and RANKL (79.5%), as well as increased IL-10 by 168.37%. Histological investigation supported these recent findings. Conclusions: Marked improvements in MTX anti-arthritic effects are seen when it is conjugated to GNPs.
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Pulmonary fibrosis is a serious ailment that may progress to lung remodeling and demolition, where the key participants in its incidence are fibroblasts responding to growth factors and cellular calcium swinging. Calcium channel blockers, like nifedipine (NFD), may represent auspicious agents in pulmonary fibrosis treatment. Unfortunately, NFD bears complicated pharmacodynamics and a diminished systemic bioavailability. Thus, the current study aimed to develop a novel, non-invasive nanoplatform for NFD for direct/effective pulmonary targeting via intratracheal instillation. A modified solvent emulsification-evaporation method was adopted for the fabrication of NFD-nanocomposites, integrating poly(D,L-lactide-co-glycolide) (PLGA), chitosan (CTS), and polyvinyl alcohol, and optimized for different physiochemical properties according to the 32 full factorial design. Additionally, the aerodynamic behavior of the nanocomposites was scrutinized through cascade impaction. Moreover, the pharmacokinetic investigations were conducted in rats. Furthermore, the optimum formulation was tested in bleomycin-induced pulmonary fibrosis in rats, wherein fibrotic and oxidative stress parameters were measured. The optimum nanocomposites disclosed a nanosized spherical morphology (226.46 nm), a high entrapment efficiency (61.81%) and a sustained release profile over 24 h (50.4%). As well, it displayed a boosted in vitro lung deposition performance with a mass median aerodynamic diameter of 1.12 µm. Pharmacokinetic studies manifested snowballed bioavailability of the optimal nanocomposites by 3.68- and 2.36-fold compared to both the oral and intratracheal suspensions, respectively. The intratracheal nanocomposites revealed a significant reduction in lung fibrotic and oxidative stress markers notably analogous to normal control besides repairing abnormality in TGF-ß/ß-catenin pathway. Our results conferred a compelling proof-of-principle that NFD-CTS-PLGA nanocomposites can function as a promising nanoparadigm for pulmonary fibrosis management.
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BACKGROUND: The prevalence of diabetes mellitus has been increased dramatically which in turn leads to complications including cardiovascular diseases, diabetic kidney disease, and substantially end-stage renal disease. METHODS: We reviewed articles discussing the pathophysiology of diabetic nephropathy with new agents that may be useful in the management of the disease. We used PubMed, Scopus, Google Scholar and the Open-access searching engines. RESULTS: The recent recommendations primarily depend on glycaemic and blood pressure control and the use of standard renin-angiotensin system blockade. Currently, the use of agents with nephroprotective effects beyond the hyperglycaemic lowering effect has been evidenced clinically. CONCLUSIONS: In his review, the pathophysiology, clinical manifestations, and lines of treatment of diabetic nephropathy are discussed. In addition, a focus on the clinical role and nephroprotective effects of the emerging therapeutic class, dipeptidyl peptidase IV (DPP-4) inhibitors, is addressed in detail.