Redox-active molecules and polymers with photovoltaic applications

The study presented in this thesis provides details regarding the synthesis and characterization of different redox active molecules which can be applied to form the active layer of photovoltaic devices. For example in chapter two, star-shaped thiophene based molecules are described and their electronic and optical properties have been investigated. In chapter three, oligomers featuring bipyridinium units with different thienyl moieties have been successfully synthesized. Preliminary electropolymerization studies are achieved. In chapter four, two different series of powerful push-pull systems containing dimethyaniline DMA moieties as a strong donating group and TCNE or TCNQ as electron accepting groups have been prepared. These series feature quinone and oligothiophene units as supporting acceptor and donor unit. In chapter five, two different series of powerful organic dyes that could improve the efficiency of DSSCs by modulating the absorption of light towards the near-IR region are achieved. The influence of π-conjugated spacers on the optical and physical properties of synthesized dyes has been investigated. Preliminary DSSCs have been fabricated from some of these systems and their properties have been compared to dye N719

Comparative effectiveness of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular disease prevention

Background: The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in the development of hypertension, and in the pathogenesis and progression of atherosclerosis, leading to cardiovascular diseases (CVD). ACEIs and ARBs inhibit the RAAS at different targets and achieve comparable BP reductions. Of the two groups, ARBs have a superior safety and tolerability profile. However, there are reports of divergent effects from ACEI and ARBs based on the meta-analyses of clinical trials. ACEIs reduce the risk of MI, cardiovascular (CV) mortality and allcause mortality, whereas ARBs do not. Clinical practice guidelines consider ACEIs and ARBs equivalent, and a comprehensive and up to date assessment of the ‘ARB paradox’ is important to inform future guidelines and ensure safe clinical practice. Objectives: The main objectives of the current thesis are: 1) to investigate the comparative effectiveness of ACEIs and ARBs for preventing CV morbidity and mortality in patients with or at high-risk of CVDs; and 2) to assess the relative contribution of BP-dependent and independent mechanisms on reducing the risk of CV morbidity and mortality, as achieved by ACEIs and ARBs. Methodologies for answering the research questions: A systematic review and meta-analysis of randomized-control trials (RCTs), was performed in addition to a random-effects meta-regression analysis. Pre-specified outcomes, including, myocardial infarction (MI), angina pectoris, stroke, heart failure (HF), all-cause mortality, and CV death were assessed. In addition, specific pre-specified subgroups of patients, including drug subclasses, comparator drugs, population clinical setting, and mean age (years), were evaluated to demonstrate the differential benefits when comparing ACEIs and ARBs. Results: The results for the meta-analysis and meta-regression analysis are divided here into four chapters (4 to 7) according to the CV outcomes for ACEIs and ARBs. In total, 97 RCTs, with 317,984 participants with or at high-risk of CVDs were included in this systematic review, over an average duration of 3.03 years. ACEIs and ARBs with risk of coronary artery disease events: The pooled data shows that there was a significant 16% (RR, 0.84; 95% CI 0.79–0.90; p<0.00001) reduction in the risk of incident MI in relation to ACEI therapy compared control group with no evidence of statistical heterogeneity among the trials (I2=0%.). In contrast, there was no overall benefit identified from ARB therapy (RR, 0.97; 95% CI 0.89-1.06; p= 0.55; I2=30%). The evidence from the direct comparison trials showed no distinction between ACEIs and ARBs in terms of MI risk (RR 1.02; 95% CI 0.95–1.09; p=0.64; I2=0%)). Furthermore, I have shown through a meta-regression analysis that nearly half (9% relative risk reduction) of the protective effect of ACEI on MI risk occurs independently of any BP lowering effect. Both ACEI and ARB therapies have no impact in terms of their capacity to reduce the risk of angina pectoris. Considerable heterogeneity was observed among the effect estimates for ACEIs and ARBs (I 2 : 58% and 61% respectively), which limits the author’s capacity to formulate definitive conclusions. ACEIs and ARBs in preventing stroke: According to this systematic review, the analyses reveal that both ACEIs and ARBs provide a reduction in stroke risk compared with placebo; by 14% (RR, 0.86; 95% CI 0.76-0.98; p=0.02; I2=26%) and 9% (RR, 0.91; 95% CI 0.85-1.00; p=0.05; I2=0%) respectively. Based on direct comparison trials, there appear to be a 4% lesser stroke lowering affect from ARB therapy than noted for ACEI (RR, 0.96; 95% CI 0.87-1.06; p=0.42; I 2=0%), but this finding did not achieve statistical significance. In the meta-regression analysis, both ACEI and ARB therapies have respective risk ratios for stroke reduction that are significantly related to the magnitude of the BP reduction. ACEIs versus ARBs for HF prevention: This overview suggests that ACEIs showed a 20% lower HF risk compared with placebo (RR, 0.80; 95% CI 0.74, 0.87; P= 0.00001). Similarly, ARBs had a 14% lower HF risk compared with placebo (RR, 0.86; 95% CI 0.80–0.92; p< 0.00001). This comparable finding was confirmed in direct comparison trials (RR,1.03; 95% CI 0.97–1.09; p=0.37; I2=0%). However, when analyzing trials with active therapy as the comparator group, ARB appeared to be beneficial, with a 13% significant reduction of HF risk, and no added benefit emerging for ACEIs. BP reduction was a major determinant of the risk reduction achieved by ACEIs, while the ARB effect occurred independently of BP reduction. ACEIs versus ARBs with risk of CV and all-cause mortality: ACEIs are associated with a 9% (RR, 0.91; 95% CI 0.86- 0.97; P=0.002) and 5% (RR, 0.95; 95% CI 0.91- 0.98; p=0.003) relative risk reduction in CV and all-cause mortality respectively. No statistical variation was apparent across the studies (I2=0%). Meanwhile, no such benefit was seen with ARB-based therapy. Direct comparison trials showed that both ACEIs and ARBs were equivalent in terms of the CV (RR, 1.04; 95% CI 0.98-1.10; p=0.16; I2=0%) and all mortality risk (RR, 1.03; 95% CI 0.98-1.08; p=0.20; I 2=0%). The magnitude of the observed risk-reduction seen with ACEIs could be attributed to the magnitude of the BP reduction. Consistent findings involving a series of sensitivity analyses were expected to support the strength of this association. Conclusions: In summary, this study used data from 317,984 participants with or at high-risk of CVDs, suggesting that ARBs are as effective as ACEIs at mitigating potential risk from CV events and mortality. The finding from the direct comparison trials also supports the view that ARBs may be slightly more protective than ACEIs against risk of stroke. The reduction in stroke risk brought about by ACEI and ARB is largely attributable to BP reduction. The magnitude of the risk reduction for HF, CV and all-mortality by ACEIs appear to have largely been driven by the magnitude of the BP reduction. The beneficial effect independent of BP reduction of ACEI on MI risk and ARB on HF risk warrants further study

Evaluation of microalbuminuria in patients with systemic sclerosis as an indicator of early renal damage and increased morbidity

AbstractIntroductionRenal involvement and systemic vascular damage have been shown to be significantly affecting prognosis in systemic sclerosis.Aim of workMicroalbuminuria detection in SSc patients as an indicator of early renal involvement and its correlation with various SSc clinical, laboratory parameters and severity of organ systems’ damage assessed by Scleroderma Assessment Questionnaire.Patients and methodsForty SSc patients (33 females and 7 males) with mean age of 27.48±12.56years and mean disease duration of 6.2±4.14years were included. Twenty-four (60%) had lSSc; 13 (32.5%) had dSSc and 3 (7.5%) patients had SSc sine scleroderma.ResultsEight (20%) had microalbuminuria and 9 (22.5%) patients had decreased creatinine clearance. Albumin/creatinine ratio was significantly higher among dSSc patients compared to those with lSSc and SSc sine scleroderma (X2=9.077; p=0.01). Albumin/creatinine ratio showed significant positive correlations with telangiectasia (r=0.322; p=0.04) and mRodnan’s skin score (r=0.352; p=0.026) and negative correlations with inter-incisor distance (r=−0.525; p=0.001) and pleurisy (r=−0.446; p=0.004). Albumin/creatinine ratio correlated significantly and positively with IMSS and IDS indices of SAQ (r=0.378, 0.32; p=0.016, 0.044, respectively). SSc patients with microalbuminuria showed significantly higher mean IDS than those without (1.058 vs. 0.631, p=0.04). No statistically significant correlations were found between creatinine clearance and the different demographic, clinical features and the indices of SAQ.ConclusionMicroalbuminuria compared to creatinine clearance may be a more sensitive indicator of early renal affection and predictor of increased morbidity

Spektrofluorimetrijsko određivanje ciklopiroks olamina prevođenjem u ternarni kompleks s Tb(III) i EDTA

A highly sensitive and selective spectrofluorimetric method was developed for the determination of ciclopirox olamine in raw material and in dosage forms. The proposed method is based on the formation of a ternary complex with Tb(III) in the presence of ethylenediaminetetraacetic acid. It was found that this complex manifests intense fluorescence at λem 489 and 545 nm with excitation at 295 nm. Different experimental parameters affecting the fluorescence intensity of the complex were carefully studied and incorporated into the procedure. Under the described conditions, the method is applicable over the concentration range of 30150 and 1070 ng mL-1 with minimum detectability of 6.7 and 0.9 ng mL-1 at λem 489 and 545 nm, respectively. The mean percentage recovery at λem 489 and λem 545 nm ranged between 98.7 and 100.2 for the pure substance, solution, and cream. Relative error of 0.10.4% and RSD up to 0.9% were estimated at λem 489 and 545 nm. A proposal of the reaction pathway is given.Razvijena je vrlo osjetljiva i selektivna spektrofluorimetrijska metoda za određivanje antimikotika ciklopiroks olamina, kao čiste supstancije i u ljekovitim oblicima. Metoda se temelji na stvaranju kompleksa s Tb(III) u prisutnosti etilendiamintetraoctene kiseline. Nakon ekscitacije pri 295 nm taj kompleks intenzivno fluorescira pri λem 489 i 545 nm. Proučavani su različiti eksperimentalni parametri koji utječu na intenzitet fluorescencije kompleksa. Za opisane uvjete metoda se može primijeniti u koncentracijskom području 30150 i 10 70 ng mL-1. Minimalna koncentracija koja se može odrediti je 6,7, odnosno 0,9 ng mL-1 na λem 489, odnosno 545 nm. Analitički povrat pri λem 489 i λem 545 nm iznosio je 98,7100,2% za čistu supstanciju, otopinu i kremu. Relativna pogreška metode je 0,10,4%, a relativna standardna devijacija 0,9%. Predložena je jednažba kemijske reakcije

Spektrofluorimetrijsko određivanje ciklopiroks olamina prevođenjem u ternarni kompleks s Tb(III) i EDTA

A highly sensitive and selective spectrofluorimetric method was developed for the determination of ciclopirox olamine in raw material and in dosage forms. The proposed method is based on the formation of a ternary complex with Tb(III) in the presence of ethylenediaminetetraacetic acid. It was found that this complex manifests intense fluorescence at λem 489 and 545 nm with excitation at 295 nm. Different experimental parameters affecting the fluorescence intensity of the complex were carefully studied and incorporated into the procedure. Under the described conditions, the method is applicable over the concentration range of 30150 and 1070 ng mL-1 with minimum detectability of 6.7 and 0.9 ng mL-1 at λem 489 and 545 nm, respectively. The mean percentage recovery at λem 489 and λem 545 nm ranged between 98.7 and 100.2 for the pure substance, solution, and cream. Relative error of 0.10.4% and RSD up to 0.9% were estimated at λem 489 and 545 nm. A proposal of the reaction pathway is given.Razvijena je vrlo osjetljiva i selektivna spektrofluorimetrijska metoda za određivanje antimikotika ciklopiroks olamina, kao čiste supstancije i u ljekovitim oblicima. Metoda se temelji na stvaranju kompleksa s Tb(III) u prisutnosti etilendiamintetraoctene kiseline. Nakon ekscitacije pri 295 nm taj kompleks intenzivno fluorescira pri λem 489 i 545 nm. Proučavani su različiti eksperimentalni parametri koji utječu na intenzitet fluorescencije kompleksa. Za opisane uvjete metoda se može primijeniti u koncentracijskom području 30150 i 10 70 ng mL-1. Minimalna koncentracija koja se može odrediti je 6,7, odnosno 0,9 ng mL-1 na λem 489, odnosno 545 nm. Analitički povrat pri λem 489 i λem 545 nm iznosio je 98,7100,2% za čistu supstanciju, otopinu i kremu. Relativna pogreška metode je 0,10,4%, a relativna standardna devijacija 0,9%. Predložena je jednažba kemijske reakcije

The Prophetic Speeches (Hadith) on Sciences and Scientists: Application of the "Text from Text and D+" Theory

This study aims to apply the theory of "Text from Text and the Plus Dimension" in the analysis of the Prophetic discourse found in the section on the virtues of knowledge and scholars from Imam Sahih al-Bukhari's book. This section covers several topics, including the virtue of gathering for the sake of learning, the superiority of a scholar over a worshipper, the excellence of jurisprudence in the religion of Allah, the acquisition of knowledge through the passing away of scholars, the merit of inviting people to Allah, the continuing benefit of beneficial knowledge after a scholar's demise, the warning against seeking knowledge for purposes other than Allah, and the Prophet seeking refuge from knowledge that brings no benefit. This is an applied analytical study that aims to elucidate the scientific miraculousness in the Prophetic hadiths and explain the meanings of the Prophetic sayings in harmony with scholars and the majority. It also seeks to derive moral lessons from the hadiths and reveal meanings that might be ambiguous or hidden using the "Text from Text and the Plus Dimension" theory in the analysis of the Prophetic discourse. The study arranges the sentences of the hadiths in the section on the virtues of knowledge and scholars from Sahih al-Bukhari's book and examines their meaning and rhetorical composition. It links them with mathematical geometric relationships such as rotation, expansion through magnification and contraction, withdrawal (beginning with the beginning), and reflection (beginning with the end). The study adopts an analytical and explanatory methodology to achieve its objectives, and the corpus of the study consists of Prophetic hadiths from the section on the virtues of knowledge and scholars from Sahih al-Bukhari's book, along with all its topics. This research builds upon two previous studies where the theory was applied to analyze the Prophetic discourse: "Inviting to Contemplate the Prophetic Discourse: Text from Text and the Extra Dimension in the Analysis of the Prophetic Discourse" (Al-Rawajfeh, 2020) and "The Theory of Text from Text and the Extra Dimension in the Analysis and Miraculousness of the Prophetic Discourse: An Application to the Book of Faith from Sahih al-Bukhari" (Al-Rawajfeh and Al-Jubbah, 2023

RELATIONSHIP OF SERUM DIPEPTIDYL PEPTIDASE-IV ACTIVITY AND ANTI-CASEIN ANTIBODIES TO GASTROINTESTINAL SYMPTOMS AMONG CHILDREN WITH AUTISM SPECTRUM DISORDER: AN EGYPTIAN STUDY

 Objectives: The objectives of the study were to assess serum dipeptidyl peptidase-IV (DPP-IV) activity in autistic children suffering from severe gastrointestinal (GI) disorder and to examine the hypothesis that there is a link between DPP-IV activity in serum and GI disorder in a subgroup of children with autism spectrum disorder (ASD).Subjects and Methods: Serum levels of casein antibodies and DPP-IV enzyme activity from 40 autistic children with chronic GI symptoms, and 40 of age-matched children without autism or gastrointestinal (GI) symptoms were assayed using enzyme-linked immunosorbent assay kits.Results: In comparison with controls, developmental milestones were delayed among autistic children. The serum DPP-IV activity was significantly lower in the studied patients (p&lt;0.05), while the mean serum levels of casein antibodies were statistically significantly higher in the studied patients (p&lt;0.01). Multiple logistic regression analysis recorded significant association between the high serum level of antibodies to casein, food selectivity and recurrent attacks of abdominal pain (p&lt;0.05), while the low serum DPP-IV enzyme activity was associated with recurrent attacks of abdominal pain in the studied patients with a prediction of 95% (p&lt;0.05).Conclusions: Serum levels of casein antibodies were higher in children with ASD, and maybe contributes to their abdominal pain, and food selectivity. Serum DPP-IV enzyme activity was lower and associated with recurrent attacks of abdominal pain in the studied patients. They may benefit from a supplemental digestive enzyme formula

G protein estrogen receptor as a potential therapeutic target in Raynaud’s phenomenon

Exaggerated cold-induced vasoconstriction can precipitate a pathogenesis called Raynaud’s phenomenon (RP). Interestingly, RP is significantly more prevalent in females than age-matched men, highlighting the potential implication of 17β-estradiol (E2) in the etio-pathogenesis of this disease. Indeed, we have previously reported that E2 stimulates the expression of vascular alpha 2C-adrenoceptors (α2C-AR), the sole mediator of cold-induced constriction of cutaneous arterioles. This induced expression occurs through the cyclic adenosine monophosphate → exchange protein activated by cAMP→ Ras-related protein 1→ c-Jun N-terminal kinase→ activator protein-1 (cAMP/Epac/Rap/JNK/AP-1 pathway). On the basis that estrogen-induced rapid cAMP accumulation and JNK activation occurs so rapidly we hypothesized that a non-classic, plasma membrane estrogen receptor was the mediator. We then showed that an impermeable form of E2, namely E2:BSA, mimics E2 effects suggesting a role for the membranous G-protein coupled estrogen receptor (GPER) in E2-induced α2C-AR expression. Our current working hypothesis and unpublished observations further cement this finding, as G1, a GPER agonist, mimics while G15, a GPER antagonist, abrogates estrogen’s effect on the expression of vascular α2C-AR. These, and other observations, highlight the potential of GPER as a tractable target in the management of RP, particularly in pre-menopausal women.APCs for this paper have been offset by a generous support from Frontiers as part of the support offered to women in pharmacology, for the specific invitation to Women in Translational Pharmacology: 2021

Asthma remodeling: The pathogenic role of matrix metalloproteinase-9

AbstractBackgroundAsthma is an airway inflammatory disease with functional and structural changes, leading to bronchial hyperresponsiveness and airflow obstruction. Pathological repair of the airways leads to these structural changes referred as airway remodeling. Matrix metalloproteinases (MMPs) are extracellular degrading enzymes that play a critical role in the remodeling process.Aim of the studyIs to study matrix metalloproteinase-9 in asthmatic patients, detecting its pathogenic role in airway remodeling.Subjects and methodsSamples of broncho-alveolar lavage (BAL) fluid and bronchoscopic biopsies from 30 asthmatic patients (10 mild, 10 moderate and 10 severe) and 10 healthy volunteers were assessed for the levels of matrix metalloproteinase-9 (MMP-9) total and differential cell count (in BAL fluid), histological airway remodeling changes and immunohistochemical expression of MMP-9 (in mucosal biopsies).ResultsBAL and tissue MMP-9 (going hand in hand with airway remodeling changes) were higher in asthmatic patients and it was significantly increased with increased severity. BAL total cell count is higher in asthmatic patients. BAL eosinophils, neutrophils, lymphocytes as well as MMP-9 positive cell count were higher in asthmatic patients and increased with severity. MMP-9 tissue expression was also strongly inversely correlated with the spirometric parameters in asthmatic patients.ConclusionsMMP-9 plays a role in airway inflammation and airway remodeling in asthma. MMP-9 is an important player in airway remodeling in bronchial asthma and may be the link between inflammation and remodeling processes