The Efficacy of Ivabradine Alone, Metoprolol Alone and Combination of Ivabradine and Metoprolol in Reducing Heart Rate Among Patients Undergoing Computed Tomography Coronary Angiography

Objectives: to determine the efficacy of Ivabradine alone, Metoprolol alone and Combination of Ivabradine and Metoprolol in reducing heart rate among patients undergoing Computed Tomography Coronary Angiography (CTCA). Methodology: it was a randomized controlled trial comprised of 200 patients. Patients undergoing CTCA having heart rates greater than 80 bpm were divided into three groups. Group A was given Ivabradine and a placebo, Group B received Metoprolol and placebo while Group C was administered with Ivabradine and Metoprolol an hour prior to the scan. The scan was carried under similar situations. Heart rate and variability was recorded before and during the scan. Results: The mean heart rate variability and mean reduction in heart rate of Group A was 3.13±1.01 and 19.02±2.05 respectively. The mean heart rate variability and mean reduction in heart rate of Group B was 4.27±1.08 and 12.11±2.45 respectively. While, the mean heart rate variability and mean reduction in heart rate of Group C was 1.88±0.42 and 25.03±2.74 respectively. Conclusion: Ivabradine is an effective and safe drug for reducing heart rate in patients having CTCA, especially among patients who are unable to tolerate calcium channel blockers and beta blockers owing to their side effects. Keywords: Ivabradine, Metoprolol, Computed tomography coronary angiography, heart rate reduction, heart rate variability

Hyperlipidemia Patterns in Newly Diagnosed Young Diabetic Patients

Objective: To analyze hyperlipidemia patterns among newly diagnosed young diabetic patients. Study Design: A descriptive cross-sectional study Place and Duration: Study was conducted in DHQ Teaching Hospital, DG Khan, Bahawal Victoria hospital, Bahawalpur, and Sheikh Zayd Hospital, Rahim Yar Khan from July 2017 to July 2018.Methodology: All the patients were young and newly diagnosed with Diabetes Mellitus. Data collection was done via non probability consecutive sampling included patients’ demographics, past medical history, co-morbidities, and lab findings were assessed. SPSS version 24 was used to analyze data. P value ≤ 0.05 was taken as significant.Results: Eighty patients were included in this study. Diabetic nephropathy, diabetic retinopathy, macrovascular complications, hyperglycemic hyperosmolar non-ketotic coma history, family history and hypertension were noted in n=12 (15%), n=6 (7.5%), n=9 (11.3%), n=1 (1.3%), n=34 (42.5%) and n=11 (13.8%) respectively. The mean hyperlipidemia, hypertriglyceridemia, of the patients was 4.54±0.52 mmol/L, 2.59±1.13 mmol/L, 1.39±0.80 mmol/L, 1.03±0.59 mmol/L respectively. Conclusion: the study has shown that the prevalence of increased levels of triglycerides is more than increased LDL cholesterol levels among these patients. As it has been established that hypertriglyceridemia is a known risk factor for causing cardiovascular disorders among diabetic patients, it should be addressed and managed accordingly at the onset of diabetes. Keywords: Hyperlipidemia, Diabetes Mellitus, low density lipoproteins, high density lipoproteins, insulin.

Chitosan/poly vinyl alcohol/graphene oxide based ph-responsive composite hydrogel films: drug release, anti-microbial and cell viability studies

The composite hydrogels were produced using the solution casting method due to the non-toxic and biocompatible nature of chitosan (CS)/polyvinyl alcohol (PVA). The best composition was chosen and crosslinked with tetraethyl orthosilicate (TEOS), after which different amounts of graphene oxide (GO) were added to develop composite hydrogels. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM) and contact angle was used to analyze the hydrogels. The samples were also evaluated for swelling abilities in various mediums. The drug release profile was studied in phosphate-buffered saline (PBS) at a pH of 7.4. To predict the mechanism of drug release, the data were fitted into kinetic models. Finally, antibacterial activity and cell viability data were obtained. FTIR studies revealed the successful synthesis of CS/PVA hydrogels and GO/CS/PVA in hydrogel composite. SEM showed no phase separation of the polymers, whereas AFM showed a decrease in surface roughness with an increase in GO content. 100 µL of crosslinker was the critical concentration at which the sample displayed excellent swelling and preserved its structure. Both the crosslinked and composite hydrogel showed good swelling. The most acceptable mechanism of drug release is diffusion-controlled, and it obeys Fick’s law of diffusion for drug released. The best fitting of the zero-order, Hixson-Crowell and Higuchi models supported our assumption. The GO/CS/PVA hydrogel composite showed better antibacterial and cell viability behaviors. They can be better biomaterials in biomedical applications

Development of antibacterial, degradable and pH-responsive chitosan/guar gum/polyvinyl alcohol blended hydrogels for wound dressing

The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels’ crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spec-troscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker–Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R2 = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Socio-legal significance of family waqf in Islamic Law: Its degradation and revival

From a Shari’ah perspective, no essential difference is noticed between public welfare waqf and a waqf created for the benefit of individuals such as descendants and family of a person, and both are treated as recommended avenues for voluntary gratuitous transfer of benefits. Over the centuries, family awqaf have degenerated due to various social and political factors. Under the influence of the English law that regards family trusts as non-charitable, family awqaf have been treated as non-charitable institutions, and have been deprived of the privileges and immunities granted to charitable awqaf. In this context, the current article discusses the essential nature of such awqaf with regard to their position in Islamic law and history as well as their social significance, and attempts to shed light on the degeneration that took place in the recent past, while exploring means of revival. It finds that the creation of endowments for specific beneficiaries such as waqf for those related to the endower is a recognised form of charity in Islamic law, that function as public serving entities directly or indirectly. Issues encountered in such awqaf do not necessitate denying their multiple advantages. Providing the necessary legal regulation and administrative framework as well as tax exemption for all awqaf could go a long way in promoting the cause of waqf

Formulation and Evaluation of a Self-Microemulsifying Drug Delivery System of Raloxifene with Improved Solubility and Oral Bioavailability

Poor aqueous solubility and dissolution limit the oral bioavailability of Biopharmaceutics Classification System (BCS) class II drugs. In this study, we aimed to improve the aqueous solubility and oral bioavailability of raloxifene hydrochloride (RLX), a BCS class II drug, using a self-microemulsifying drug delivery system (SMEDDS). Based on the solubilities of RLX, Capryol 90, Tween 80/Labrasol ALF, and polyethylene glycol 400 (PEG-400) were selected as the oil, surfactant mixture, and cosurfactant, respectively. Pseudo-ternary phase diagrams were constructed to determine the optimal composition (Capryol 90/Tween 80/Labrasol ALF/PEG-400 in 150/478.1/159.4/212.5 volume ratio) for RLX-SMEDDS with a small droplet size (147.1 nm) and stable microemulsification (PDI: 0.227). Differential scanning calorimetry and powder X-ray diffraction of lyophilized RLX-SMEDDS revealed the loss of crystallinity, suggesting a molecularly dissolved or amorphous state of RLX in the SMEDDS formulation. Moreover, RLX-SMEDDS exhibited significantly higher saturation solubility and dissolution rate in water, simulated gastric fluid (pH 1.2), and simulated intestinal fluid (pH 6.8) than RLX powder. Additionally, oral administration of RLX-SMEDDS to female rats resulted in 1.94- and 1.80-fold higher area under the curve and maximum plasma concentration, respectively, than the RLX dispersion. Collectively, our findings suggest SMEDDS is a promising oral formulation to enhance the therapeutic efficacy of RLX

Multifaced Assessment of Antioxidant Power, Phytochemical Metabolomics, In-Vitro Biological Potential and In-Silico Studies of Neurada procumbens L.: An Important Medicinal Plant

This work was undertaken to explore the phytochemical composition, antioxidant, and enzyme-inhibiting properties of Neurada procumbens L. extracts/fractions of varying polarity (methanol extract and its fractions including n-hexane, chloroform, n-butanol, and aqueous fractions). A preliminary phytochemical study of all extracts/fractions, HPLC-PDA polyphenolic quantification, and GC-MS analysis of the n-hexane fraction were used to identify the phytochemical makeup. Antioxidant (DPPH), enzyme inhibition (against xanthine oxidase, carbonic anhydrase, and urease enzymes), and antibacterial activities against seven bacterial strains were performed for biological investigation. The GC-MS analysis revealed the tentative identification of 22 distinct phytochemicals in the n-hexane fraction, the majority of which belonged to the phenol, flavonoid, sesquiterpenoid, terpene, fatty acid, sterol, and triterpenoid classes of secondary metabolites. HPLC-PDA analysis quantified syringic acid, 3-OH benzoic acid, t-ferullic acid, naringin, and epicatechin in a significant amount. All of the studied extracts/fractions displayed significant antioxidant capability, with methanol extract exhibiting the highest radical-scavenging activity, as measured by an inhibitory percentage of 81.4 ± 0.7 and an IC50 value of 1.3 ± 0.3. For enzyme inhibition experiments, the n-hexane fraction was shown to be highly potent against xanthine oxidase and urease enzymes, with respective IC50 values of 2.3 ± 0.5 and 1.1 ± 0.4 mg/mL. Similarly, the methanol extract demonstrated the strongest activity against the carbonic anhydrase enzyme, with an IC50 value of 2.2 ± 0.4 mg/mL. Moreover, all the studied extracts/fractions presented moderate antibacterial potential against seven bacterial strains. Molecular docking of the five molecules β-amyrin, campesterol, ergosta-4,6,22-trien-3β-ol, stigmasterol, and caryophyllene revealed the interaction of these ligands with the investigated enzyme (xanthine oxidase). The results of the present study suggested that the N. procumbens plant may be evaluated as a possible source of bioactive compounds with multifunctional therapeutic applications