Antimicrobial screening involving Helicobacter pylori of nano-therapeutic compounds based on the amoxicillin antibiotic drug.

Nano-structure Cu(II) complex [Cu(AMAB)2 ]Cl2 with Schiff base (AMAB) derived from the condensation between 4-(dimethylamino)benzaldehyde and amoxicillin trihydrate was prepared. (AMAB) Schiff base and its Cu(II) complex were identified and confirmed by different physicochemical techniques. The Schiff base (AMAB) was coordinated to copper ion through carbonyl oxygen and imine nitrogen donor sites. X-ray powder diffraction shows a cubic crystal system of the Cu(II) complex. The density functional theory was used to optimize the structure geometries of the investigated compounds. The molecular docking of the active amino acids of the investigated proteins' interactions with the tested compounds was evaluated. The bactericidal or bacteriostatic effect of the compounds was screened against some bacterial strains. The activity of Cu-chelate against Gram-negative bacteria was mainly more effective than its (AMAB) ligand and vice versa in the case of Gram-positive bacteria. The biological activity of the prepared compounds with biomolecules calf thymus DNA (CT-DNA) was determined by electronic absorption spectra and DNA gel electrophoresis technique. All studies revealed that the Cu-chelate derivative exhibited better binding affinity to both CT-DNA than the AMAB and amoxicillin itself. The anti-inflammatory effect of the designed compounds was determined by testing their protein denaturation inhibitory activity spectrophotometrically. All obtained data supported that the designed nano-Cu(II) complex with Schiff base (AMAB) is a potent bactericide against H. pylori, and exhibits anti-inflammatory activity. The dual inhibition effects of the designed compound represent a modern therapeutic approach with extended spectrum of action. Therefore, it can act as good drug target in antimicrobial and anti-inflammtory therapies. Finally, H. pylori resistance to amoxicillin is absent or rare in many countries, thus amoxicillin nanoparticles may be beneficial for countries where amoxicillin resistance is reported.

Epidural levobupivacaine versus a combination of levobupivacaine and dexamethasone in patients receiving epidural analgesia.

BACKGROUND AND AIMS: The use of dexamethasone as an adjuvant to local anesthetic rarely has been described. Some studies have demonstrated the analgesic effect of local spinal and systemic corticosteroids in combination with bupivacaine. It works by decreasing inflammation and blocking transmission of nociceptive C-fibers and by stopping the ectopic discharge of the nerve. The aim of this randomized controlled trial was to compare the efficacy of epidural levobupivacaine alone versus a combination of levobupivacaine with dexamethasone for labor analgesia. MATERIAL AND METHODS: This prospective double-blind trial included the 60 primigravidas during vaginal delivery with a cervical dilatation ≥4 cm and 50% effacement randomly assigned to one of two groups - Group A (n=30): epidural levobupivacaine 0.125% in normal saline in a total volume of 15 mL and Group B (n=30): epidural levobupivacaine 0.125% in normal saline combined with dexamethasone 4 mg in a total volume of 15 mL. At first request of analgesia, 10 mL of 0.125% levobupivacaine was administrated through epidural catheter. Further analgesia was provided with 8 mL of 0.125% levobupivacaine hourly. Primary outcome measure was the duration of epidural analgesia. Secondary outcome measures include pain score by Visual Analog Scale score before the block and 15 min following it, the total amount of levobupivacaine used, Apgar score and umbilical vein blood gas analysis, maternal satisfaction, and side effects recorded. RESULTS AND CONCLUSION: The duration of epidural analgesia was significantly longer (P < 0.05) upon adding dexamethasone to levobupivacaine. Total epidural levobupivacaine consumption was significantly lower (P = 0.05) in Group B. There were no statistical differences between the two groups regarding hemodynamics, pain score, neonatal outcome, and complications. Epidural dexamethasone plus levobupivacaine prolongs the duration of epidural analgesia during management of labor pain with hemodynamic stability and limited maternal and neonatal adverse effects.

Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous solid dispersion.

Most active pharmaceutical ingredients (APIs) suffer from poor water solubility, often keeping them from reaching patients. To overcome the issues of poor drug solubility and subsequent low bioavailability, amorphous solid dispersions (ASDs) have garnered much attention. Cellulose ester derivatives are of interest for ASD applications as they are benign, sustainable-based, and successful in commercial drug delivery systems, e.g. in osmotic pump systems and as commercial ASD polymers. Synthesis of carboxy-pendant cellulose esters is a challenge, due in part to competing reactions between carboxyls and hydroxyls, forming ester crosslinks. Herein we demonstrate proof-of-concept for a scalable synthetic route to simple, yet highly promising ASD polymers by esterifying cellulose polymers through ring-opening of cyclic succinic or glutaric anhydride. We describe the complexity of such ring-opening reactions, not previously well-described, and report ways to avoid gelation. We report synthesis, characterization, and preliminary in vitro ASD evaluations of fifteen such derivatives. Synthetic routes were designed to accommodate these criteria: no protecting groups, no metal catalysts, mild conditions with standard reagents, simple purification, and one-pot synthesis. Finally, these designed ASD polymers included members that maintained fast-crystallizing felodipine in solution and release it from an ASD at rather high 20 % drug loading (DL).

Effectiveness of ultrasound-guided rhomboid intercostal and sub-serratus block for perioperative analgesia in male patients undergoing combined power-assisted liposuction with pull-through excision of the gland for breast definition and reshaping.

BACKGROUND: The newly introduced ultrasound guided interfacial rhomboid intercostal and sub-serratus (RISS) block technique demonstrated promising efficacy in managing perioperative pain among patients undergoing abdominal and thoracic procedures. Thus, this study investigated the efficiency of bilateral ultrasound-guided RISS (US-RISS) as a perioperative pain control technique in male subjects receiving gynecomastia surgery. METHODS: This prospective randomized study involved sixty patients who underwent gynecomastia surgery. Individuals were randomly divided into two groups: the RISS group (N.=30) and the control group (N.=30). After anesthesia induction, the patients received bilateral US-RISS using 40 mL of 0.25% levobupivacaine, or conventional intravenous analgesia with no intervention, respectively. The primary outcome was the overall morphine consumption in 24 hours, and the secondary endpoints involved the time elapsed till rescue analgesia was requested, the quality of recovery after 24 hours and side effects' incidence. RESULTS: Morphine consumption was noticeably decreased in the RISS group compared to the control group, with 14.07±4.91 mg and 35.83±1.70 mg mean values, respectively (P<0.001). Furthermore, in the RISS group, the initial rescue analgesia request occurred significantly later than in the control group, with mean values of 15.58±1.41 hours and 0.96±0.63 hours, respectively (P<0.001). Additionally, within the RISS group, there was a high quality of recovery observed, with a low incidence of opioid-related adverse events in comparison to the control group. CONCLUSIONS: Bilateral US-RISS block is a beneficial intervention in gynecomastia surgery for pain management and improves the quality of recovery.

Reductive amination of oxidized hydroxypropyl cellulose with ω-aminoalkanoic acids as an efficient route to zwitterionic derivatives.

Zwitterionic polymers, with their equal amounts of cationic and anionic functional groups, have found widespread utility including as non-fouling coatings, hydrogel materials, stabilizers, antifreeze materials, and drug carriers. Polysaccharide-derived zwitterionic polymers are attractive because of their sustainable origin, potential for lower toxicity, and possible biodegradability, but previous methods for synthesis of zwitterionic polysaccharide derivatives have been limited in terms of flexibility and attainable degree of substitution (DS) of charged entities. We report herein successful design and synthesis of zwitterionic polysaccharide derivatives, in this case based on cellulose, by reductive amination of oxidized 2-hydroxypropyl cellulose (Ox-HPC) with ω-aminoalkanoic acids. Reductive amination products could be readily obtained with DS(cation) (= DS(anion)) up to 1.6. Adduct hydrophilic/hydrophobic balance (amphiphilicity) can be influenced by selecting the appropriate chain length of the ω-aminoalkanoic acid. This strategy is shown to produce a range of amphiphilic, water-soluble, moderately high glass transition temperature (Tg) polysaccharide derivatives in just a couple of efficient steps from commercially available building blocks. The adducts were evaluated as crystallization inhibitors. They are strong inhibitors of crystallization even for the challenging, poorly soluble, fast-crystallizing prostate cancer drug enzalutamide, as supported by surface tension and Flory-Huggins interaction parameter results.

Paracetamol Versus Ondansetron for Prevention of Postoperative Shivering in Liposuction Surgeries Under Combined General Epidural Anaesthesia: A Randomized Controlled Trial.

Objective: Postoperative shivering (POS) is considered one of the most common complications that is encountered by the anaesthetists worldwide. Despite using several treatment options, there has not been a clear consensus regarding this issue. This trial was conducted to investigate the efficacy and safety of paracetamol and ondansetron in preventing POS in patients undergoing liposuction procedures under combined general epidural anaesthesia. Methods: One hundred twenty patients scheduled for liposuction were randomly allocated to one of three groups: group P (paracetamol group) which received 1 g paracetamol intravenously, group O (ondansetron group) which received 8 mg of ondansetron intravenously, and group S (saline group), which received 100 mL normal saline intravenously; all medications were given postoperatively. The primary outcome was the incidence of POS, and the secondary outcomes included shivering score, tympanic temperature, and the occurrence of side effects. Results: The incidence of occurrence of POS was found to be lower in groups P and O compared to group S with values of 25% and 37.50% vs. 77.50%, respectively, with a P value <0.001. Additionally, the severity of POS was found to be lower in groups P and O compared to group S (P <0.001). Tympanic temperature and complications were comparable between the groups with no significant differences. Conclusion: Prophylactic use of paracetamol or ondansetron at the end of the procedure was shown to be of great value in reducing the incidence and severity of POS, with no statistically significant difference between the paracetamol and ondansetron groups. Moreover, no significant drawbacks were reported as a result of using these medications.

Performance of Melatonin as Prophylaxis in Geriatric Patients with Multifactorial Risk for Postoperative Delirium Development: A Randomized Comparative Study.

OBJECTIVE: Postoperative delirium is the worst patient outcome. Elderly patients undergoing orthopaedic procedures under general anaes- thesia are highly liable to experience delirium. Several studies supported melatonin use for the prevention of delirium. This work evaluated the prophylactic efficiency of melatonin for postoperative delirium in patients with multifactorial risk for developing delirium as elderly undergoing orthopaedic trauma surgery under general anaesthesia. METHODS: This double-blinded prospective randomized comparative study was conducted on 80 elderly patients subjected to orthopaedic interventions under general anaesthesia. Patients were randomized into group M (Melatonin group) and group NM (Non-melatonin group). Group M received 5 mg melatonin while group NM received placebo. The study drugs were given preoperatively and for the first 3 postop- erative days. For the incidence of delirium, patients were evaluated using the Abbreviated Mental Test. The Pain Assessment in Advanced Dementia, sedation scores, and changes in hemodynamics were recorded. RESULTS: The incidence of delirium was significantly lower postoperatively in M group (25%) relative to NM group (52.5%) (P <ƒ .001, OR=2.3. 95% CI=-0.44,+1.23). Abbreviated Mental Test scores at postanaesthesia care unit and day 0 showed a highly significant dif- ferences. However, Abbreviated Mental Test scores had no significant difference within the 3 postoperative days. Heart rate was significantly lower in M group after 50 minutes from the start of surgery. Mean blood pressure, Pain Assessment in Advanced Dementia, and sedation scores showed insignificant differences. CONCLUSION: Perioperative melatonin treatment could reduce the incidence of postoperative delirium in the studied population, and it could be considered a prophylactic medication.

Nanobiotic formulations as promising advances for combating MRSA resistance: susceptibilities and post-antibiotic effects of clindamycin, doxycycline, and linezolid.

Antimicrobial activity and post-antibiotic effects (PAEs) are both important parameters in determination of the dosage regimen of antimicrobial agents. In the present study, antimicrobial activity and PAEs of clindamycin, doxycycline, linezolid, and their nanobiotic formulations were evaluated against two methicillin resistant Staphylococcus aureus clinical isolates (MRSA) encoded (MRSA-S1 and MRSA-S2). Nanobiotic formulations increased the susceptibility of MRSA isolates by 4-64 folds as compared to their conventional ones. The PAE values were determined after exposure of MRSA isolates for 1 h to 10× the MICs of the tested antibiotics. The duration of PAEs were recorded after bacterial growth in Mueller Hinton broth (MHB) free from antibiotic has been restored. The PAE values for MRSA-S1 were 2.5 h for the conventional antibiotics. However, the PAEs for nanobiotics were 4 h for both clindamycin and linezolid, while 3 h for doxycycline. For MRSA-S2, linezolid and linezolid nanobiotics PAEs were 3 h. PAEs of clindamycin and clindamycin nanobiotics were 3.75 h and 4 h, respectively. Doxycycline and doxycycline nanobiotics revealed the same PAEs patterns of 3.5 h. The findings of the current study may positively influence the pharmacodynamics of the antibiotics and consequently the dosage regimen of nanobiotics as well as on their clinical outcome.

Endotracheal intubation in patients undergoing open abdominal surgery in the lateral position: a comparison between the intubating video stylet and fiberoptic intubating bronchoscopy.

BACKGROUND: Some situations compel anesthetists to execute endotracheal intubation in the lateral position. We compared elective endotracheal intubation in the lateral decubitus position using the video stylet (VS) device with the fiberoptic (FO) bronchoscope device in patients undergoing abdominal surgery. METHODS: Overall, 50 patients were enrolled in this prospective, randomized study. They were randomly classified into the VS intubation or FO intubating bronchoscope group. After anesthesia induction, patients were placed in the lateral decubitus position, and a single investigator well-versed with the use of the VS and FO bronchoscope performed the intubation. The primary outcome was the time taken for intubation. Secondary outcomes included the intubation success rate, hemodynamic response at specific time points and perioperative complications. RESULTS: The average time taken for intubation was significantly lesser in the VS group than in the FO group, with values of 39.5 ± 10.0 and 75.6 ± 16.2 s, respectively (P < 0.001). Incidences of a successful first attempt of intubation in the VS and FO groups were 88% and 100%, respectively, showing no significant difference. There was a negligible difference in complications between the groups, except sore throat, which showed a higher incidence in the VS group than in the FO group (P = 0.002). CONCLUSIONS: In laterally positioned patients, elective endotracheal intubation with VS provides less intubation time; however, its use is accompanied by a significant increase in the hemodynamic response after intubation and an increased incidence of sore throat.

In Vitro Evaluation of Antimicrobial Activity and Cytotoxicity of Different Nanobiotics Targeting Multidrug Resistant and Biofilm Forming Staphylococci.

Antibiotic-resistant and biofilm-forming bacteria have surprisingly increased over recent years. On the contrary, the rate of development of new antibiotics to treat these emerging superbugs is very slow. Therefore, the aim of this study was to prepare novel nanobiotic formulations to improve the antimicrobial activity of three antibiotics (linezolid, doxycycline, and clindamycin) against Staphylococci. Antibiotics were formulated as nanoemulsions and evaluated for their antimicrobial activities and cytotoxicities. Cytotoxicity of the conventional antibiotics and nanobiotics was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on rat hepatocytes. Half-maximal inhibitory concentration (IC50) was estimated from an experimentally derived dose-response curve for each concentration using GraphPad Prism software. Upon quantitative assessment of Staphylococcus biofilm formation, eighty-four isolates (66.14 %) were biofilm forming. Linezolid and doxycycline nanobiotics exhibited promising antibacterial activities. On the contrary, clindamycin nanobiotic exhibited poor antibacterial activity. Minimum biofilm inhibitory concentrations showed that 73.68 %, 45.6%, and 5.2% of isolates were sensitive to linezolid, doxycycline, and clindamycin nanobiotics, respectively. Results of this study revealed that antibiotics loaded in nanosystems had a higher antimicrobial activity and lower cytotoxicities as compared to those of conventional free antibiotics, indicating their potential therapeutic values.