Effectiveness of Topical Ketorolac in Post-hemorrhoidectomy Pain Management: A Clinical Trial.

Background: Postoperative pain management is one of the major challenges of surgeons and anesthesiologists. Objectives: This study aimed to determine the efficacy of topical ketorolac in post-hemorrhoidectomy pain management. Methods: This clinical trial was conducted on 84 candidates for hemorrhoidectomy (grade-II hemorrhoids) who visited Ali ibn Abi-Talib hospital of Rafsanjan, Kerman, Iran (2020 - 2021). The participants were selected through convenience sampling and randomly assigned to three groups of 28. The subjects were treated in topical (4 mL 0.5% Marcaine + 1 mL ketorolac at the surgical site), intramuscular (4 mL 0.5% Marcaine at the surgical site + 1 mL ketorolac intramuscularly), and control (4 mL 0.5% Marcaine at the surgical site) groups. Pain intensity was measured using the Numerical Pain Rating Scale 1, 6, 12, and 24 hours after surgery. The obtained data were analyzed using two-way repeated measures analysis of variance. Results: Female and male patients constituted 46.4% and 53.6% of the participants, respectively. The mean pain intensity was significantly lower in the topical group than in intramuscular and control treatments in all four stages of pain assessment (P < 0.001). Some participants were treated with pethidine due to high pain intensity. However, the mean pain intensity gradually reduced over time in all three groups. Conclusions: Study findings suggested that the topical administration of ketorolac and Marcaine was more effective than Marcaine used alone for relieving pain in patients undergoing hemorrhoidectomy.

Well-Defined pH-Responsive Self-Assembled Block Copolymers for the Effective Codelivery of Doxorubicin and Antisense Oligonucleotide to Breast Cancer Cells.

The worldwide steady increase in the number of cancer patients motivates the development of innovative drug delivery systems for combination therapy as an effective clinical modality for cancer treatment. Here, we explored a design concept based on poly(ethylene glycol)-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(2-hydroxyethyl methacrylate-formylbenzoic acid) [PEG-b-PDMAEMA-b-P(HEMA-FBA)] for the dual delivery of doxorubicin (DOX) and GTI2040 (an antisense oligonucleotide for ribonucleotide reductase inhibition) to MCF-7 breast cancer cells. PEG-b-PDMAEMA-b-PHEMA, the precursor copolymer, was prepared through chain extensions from a PEG-based macroinitiator via two consecutive atom transfer radical polymerization (ATRP) steps. Then, it was modified at the PHEMA block with 4-formylbenzoic acid (FBA) to install reactive aldehyde moieties. A pH-responsive polymer-drug conjugate (PDC) was obtained by conjugating DOX to the polymer structure via acid-labile imine linkages, and subsequently self-assembled in an aqueous solution to form DOX-loaded self-assembled nanoparticles (DOX-SAN) with a positively charged shell. DOX-SAN condensed readily with negatively charged GTI2040 to form GTI2040/DOX-SAN nanocomplexes. Gel-retardation assay confirmed the affinity between GTI2040 and DOX-SAN. The GTI2040/DOX-SAN nanocomplex at N/P ratio of 30 exhibited a volume-average hydrodynamic size of 136.4 nm and a zeta potential of 21.0 mV. The pH-sensitivity of DOX-SAN was confirmed by the DOX release study based on the significant cumulative DOX release at pH 5.5 relative to pH 7.4. Cellular uptake study demonstrated favorable accumulation of GTI2040/DOX-SAN inside MCF-7 cells compared with free GTI2040/DOX. In vitro cytotoxicity study indicated higher therapeutic efficacy of GTI2040/DOX-SAN relative to DOX-SAN alone because of the downregulation of the R2 protein of ribonucleotide reductase. These outcomes suggest that the self-assembled pH-responsive triblock copolymer is a promising platform for combination therapy, which may be more effective in combating cancer than individual therapies.

Fournier's gangrene after missed acute perforated appendicitis: A case report.

Fournier's gangrene (FG) is a rare progressive necrotizing fasciitis (NF) with high mortality rate. This case report describes a young patient with FG with no known history of disease or invasive therapeutic interventions.

The effect of pregabalin on postdural puncture headache among patients undergoing elective cesarean section: A randomized controlled trial.

INTRODUCTION: Post-dural puncture headache (PDPH) is one of the most common problems of cesarean section. The present study aimed to evaluate the effect of pregabalin on PDPH among patients undergoing elective cesarean section. MATERIALS AND METHODS: This double-blind clinical trial was performed on 136 patients undergoing elective cesarean section referred to Shahid Motahari Teaching Hospital in Urmia in northwestern Iran from February 1 to December 20, 2020. Patients were selected by convenience sampling method and randomly divided into two groups of intervention and control (N = 68 people each group). The presence of PDPH and its severity were recorded in the checklist based on the VAS, and conventional treatments were prescribed in the case of occurrence of the PDPH. The PDPH severity was also assessed by the patient using the 10-cm Visual Analog Scale (VAS). RESULTS: The mean age of participants was 27.82 years. A total of 29 people suffered from hypotension. Regarding pain severity, the mean pain score in the intervention group was significantly lower than the control group (p = 0.01). Results also showed that the frequency of PDPH in the intervention group was significantly lower than the placebo group (4.4% vs. 11.8%; p = 0.019). There was no significant difference between intervention and control groups in terms of demographic characteristics (p > 0.05). CONCLUSION: Results of the present study showed the use of oral pregabalin at night before spinal anesthesia in patients undergoing elective cesarean(C-) section had a preventive effect on the severity and incidence of PDPH.

Maximizing the grafting of zwitterions onto the surface of ultrafiltration membranes to improve antifouling properties.

Superhydrophilic zwitterions have been extensively exploited for surface modification to improve antifouling properties. However, it remains challenging to form layers of < 20 nm with high zwitterion content on the surfaces with different degrees of hydrophilicity. We demonstrate that amine-functionalized sulfobetaine (SBAm) can be co-deposited with dopamine on ultrafiltration (UF) membranes, leading to a thickness of 10 nm to 50 nm and an SBAm content of up to 31 mass% in the coating layers. The covalently grafted SBAm is stable underwater and improves the antifouling properties, as evidenced by the lower trans-membrane pressure required to retain targeted water fluxes than that required for the pristine membranes. The SBAm is also more effective than conventionally used sulfobetaine methacrylate (SBMA) for the zwitterion grafting on the surface to improve antifouling properties.

Well-Defined Diblock Poly(ethylene glycol)-b-Poly(ε-caprolactone)-Based Polymer-Drug Conjugate Micelles for pH-Responsive Delivery of Doxorubicin.

Nanoparticles have emerged as versatile carriers for various therapeutics and can potentially treat a wide range of diseases in an accurate and disease-specific manner. Polymeric biomaterials have gained tremendous attention over the past decades, owing to their tunable structure and properties. Aliphatic polyesters have appealing attributes, including biodegradability, non-toxicity, and the ability to incorporate functional groups within the polymer backbone. Such distinctive properties have rendered them as a class of highly promising biomaterials for various biomedical applications. In this article, well-defined alkyne-functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) diblock copolymer was synthesized and studied for pH-responsive delivery of doxorubicin (DOX). The alkyne-functionalized PEG-b-PCL diblock copolymer was prepared by the synthesis of an alkyne-functionalized ε-caprolactone (CL), followed by ring-opening polymerization (ROP) using PEG as the macroinitiator. The alkyne functionalities of PEG-b-PCL were modified through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction to graft aldehyde (ALD) groups and obtain PEG-b-PCL-g-ALD. Subsequently, DOX was conjugated on PEG-b-PCL-g-ALD through the Schiff base reaction. The resulting PEG-b-PCL-g-DOX polymer-drug conjugate (PDC) self-assembled into a nano-sized micellar structure with facilitated DOX release in acidic pH due to the pH-responsive linkage. The nanostructures of PDC micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). In vitro studies of the PDC micelles, revealed their improved anticancer efficiency towards MCF-7 cells as compared to free DOX.

PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA.

As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.

Layer-by-layer preparation of polyelectrolyte multilayer nanocapsules via crystallized miniemulsions.

Well-defined polyelectrolyte multilayer nanocapsules (NCs) are synthesized by layer-by-layer deposition of poly(acrylic acid) and poly(allylamine hydrochloride) over crystallized miniemulsion nanoparticles, followed by shell crosslinking and template removal. This synthetic approach allows well-controlled dimensions of NCs due to the high colloidal stability of the templates, and may also permit a broad composition range of NCs because of the mild conditions for template removal.

Stimuli-responsive hydrogels for manipulation of cell microenvironment: From chemistry to biofabrication technology.

Native tissues orchestrate their functions by complex interdependent cascades of biochemical and biophysical cues that vary spatially and temporally during cellular processes. Scaffolds with well-tuned structural, mechanical, and biochemical properties have been developed to guide cell behavior and provide insight on cell-matrix interaction. However, static scaffolds very often fail to mimic the dynamicity of native extracellular matrices. Stimuli-responsive scaffolds have emerged as powerful platforms that capture vital features of native tissues owing to their ability to change chemical and physical properties in response to cytocompatible stimuli, thus enabling on-demand manipulation of cell microenvironment. The vast expansion in biorthogonal chemistries and stimuli-responsive functionalities has fuelled further the development of new smart scaffolds that can permit multiple irreversible or reversible spatiotemporal modulation of cell-directing cues, thereby prompting in-depth studies to interpret the decisive elements that regulate cell behavior. Integration of stimuli-responsive hydrogels with current biofabrication technologies has allowed the development of dynamic scaffolds with organizational features and hierarchical architectures similar to native tissues. This review highlights the progress achieved using stimuli-responsive hydrogels in fundamental cell biology studies, with particular emphasis on the interplay between chemistry, biomaterials design, and biofabrication technologies for manipulation of cell microenvironment.