Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study.

Background: Neuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression. Aim: To investigate the mechanistic pathways of high dose atorvastatin in MDD. Patients and methods: This trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS<17 and>7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured. Results: The atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine (p = 0.03, and p = 0.005), respectively. Conclusion: These results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3. Clinical Trial Registration: clinicaltrials.gov, identifier NCT05792540.

Correlation between depression scores and serum NF-ĸB/NLRP3 axis, biotinidase, and HMGB1 after treatment with isotretinoin in patients with acne vulgaris.

BACKGROUND: Acne vulgaris (AV) is an inflammatory skin disorder leading to scars and discomfort, its intensity has major psychological consequences such as depression. AIM: To investigate the effect of isotretinoin (ISO) on NF-κB/NLRP3, biotinidase, and HMGB and correlation with depression. PATIENTS AND METHODS: This was a case-control study that involved two groups. Group 1 is 20 healthy control, and group 2 is 20 patients diagnosed with AV according to Global Acne Grading System (GAGS) and received 20 mg ISO for 2 months. Before and after therapy, the Hamilton Depression Rating Scale (HDRS) was applied to assess each participant's level of depression. Nuclear factor kappa B (NF-ĸB), biotinidase, high mobility group box protein (HMGB1), nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP-3) were measured in serum samples. RESULTS: There was no significant difference in all measured markers of healthy group before and after 2 months. Regarding group 2, there was a statistically significant decrease in all measured markers after 2 months of treatment and significant correlations between GAGS, NF-ĸB, HMGB1, NLRP3, biotinidase, and depression score. CONCLUSION: Increased GAGS, HMGB1, NLRP3, and biotinidase were associated with depression severity in AV patients and ISO treatment significantly reduced these parameters and reduced depressive symptoms.

To B or not to B: the application of uterine compression sutures to reduce blood loss after myomectomy.

Introduction: The aim was to assess the hemostatic impact of B-Lynch sutures following an open myomectomy for efficacy. Material and methods: In this prospective clinical research, performed in Alazhar university hospitals (Al-Hussain, Damietta, Assiut) and Minia University Maternity Hospital, 250 women scheduled for open myomectomy between January 2021 and January 2023 had multiple fibroid uteri with uterine sizes corresponding to 12-22 weeks. There were two groups of women. Group I (125) underwent standard open myomectomy surgery, whereas Group II (125) underwent normal open laparotomy surgery followed by B-Lynch sutures. Certain inclusion and exclusion criteria were applied to every patient. We recorded vital data, length of the procedure, complications (bleeding during the procedure, bleeding from multiple bites, bladder injury, fever, wound infection), complete blood count before and after surgery, need for blood transfusion, postoperative vital data, time until ambulation, passing flatus, and ability to eat and drink, as well as the amount of blood lost during and after the procedure. Results: There was no statistically significant difference between the two groups in age, parity, weight, number of fibroids, or uterine size as measured by ultrasonography. Between groups I and II, there was a significant difference in the average intraoperative blood loss (Group I lost 562.6 ml, whereas Group II lost 411.3 ml) as well as the mean blood loss following surgery (205 ±82 ml in Group I and 117 ±41 ml in Group II). No significant difference was observed in the mean length of hospital stay between groups I and II (2 ±0.3 days and 2 ±0.6 days, respectively). Conclusions: Using a B-Lynch suture can help minimize blood loss during and after an open myomectomy. Therefore, if the uterus is large and has a lot of fibroids, it is recommended to be done frequently.

Formulation, optimization and evaluation of ocular gel containing nebivolol Hcl-loaded ultradeformable spanlastics nanovesicles: In vitro and in vivo studies.

The study aims to improve the ocular delivery of Nebivolol HCL (NBV) belonging to the Biopharmaceutics classification system (BCSII) by using spanlastic nanovesicles (SNVs) for ophthalmic delivery and incorporating them into hydroxypropyl methylcellulose gel with ketorolac tromethamine (KET) as an anti-inflammatory to improve glaucoma complications like Conjunctivitis. SNVs were prepared by ethanol injection technique using span (60) as a surfactant and labrasol as an edge activator (EA). The impact of formulation factors on SNVs properties was investigated using a Box-Behnken design. In vitro evaluations showed that the formulations (F1, F4, and F14), containing Span 60 and labrasol as EA (25%, 50%, and 25%), exhibited high EE% with low PS and high ZP and DI. Additionally, 61.72 ± 0.77%, 58.97 ± 1.44%, and 56.20 ± 2.32% of the NBV amount were released from F1, F4, and F14 after 5 h, compared to 93.94 ± 1.21% released from drug suspension. The selected formula (G1), containing F1 in combination with KET and 2% w/w HPMC, exhibited 76.36 ± 0.90% drug release after 12 h. Ex vivo Confocal laser scanning revealed a high penetration of NBV-SNVs gel that ascertained the results of the in-vitro study. In vivo studies showed a significant decrease in glaucoma compared to drug suspension, and histopathological studies showed improvement in glaucomatous eye retinal atrophy. G1 is considered a promising approach to improving ocular permeability, absorption, and anti-inflammatory activity, providing a safer alternative to current regimens.

Recognition of 7 genes signature (Cirrhosis Risk Score) in the diagnosed non-responders to DAAs therapy by intra-PBMCs nested HCV RNA PCR.

BACKGROUND AND AIMS: Predictors of chronic HCV response to oral antiviral therapy (OAT) are related to host genetic variations. Single nucleotide polymorphisms (SNP) and alleles variations of host genes in association with hepatic fibro-cirrhotic changes have a distinct role in OAT outcomes. The current research evaluated the association of Cirrhosis-Risk-Scores (CRS) values, based on the correlation of seven genes signature-SNPs, with sonographic liver parenchymal changes in determining OAT outcomes. METHODS: All study subjects (n = 54) were recruited three months after completing OAT and classified into three groups. Group I (n = 21) had negative HCV PCR, group II (n = 17) showed positive solitary intra-PBMCs HCV infection, and group III(n = 16) was serum HCV RNA PCR-positive. All study-population were subjected to examination by hepatic-ultrasound (US), FIB-4-scoring, and screening for 7 gene-signature that addressed CRS values as low, intermediate, and high depending on gene SNPs identification. RESULTS: Group I showed a significant association with low CRS values compared to other groups (P < 0.001). Solitary intra- PBMCs HCV infection in group II was significantly combined with intermediate CRS values in comparison to groups I and III (P < 0.001). The high CRS values were significantly found in group III when compared to groups I and II (P < 0.01). On US imaging, low CRS values were common in normally appeared hepatic parenchyma (P < 0.001) and high CRS values were frequent in coarse-liver (P < 0.001), while bright-liver-tissues appearance was mainly detected in the intermediate CRS category (P = 0.09). On FIB-4 scoring, high CRS value were associated with hepatic fibro-cirrhosis compared to intermediate (P < 0.001) and low (P = 0.08) CRS-categories. CONCLUSION: The current study concluded the association of (a) high CRS values with coarse liver in viral-RNA serologic relapse, (b) low CRS values with normal liver tissues in sustained virologic response (SVR), (c) intermediate CRS values with bright liver in solitary PBMCs relapse.

Resective epilepsy surgery in a limited-resource settings: A cohort from a multi-disciplinary epilepsy team in a developing country.

Background: Multidisciplinary pre-surgical evaluation is vital for epilepsy surgery decision and outcomes. Resective epilepsy surgery with assisted monitoring is currently a standard treatment for focal drug resistant epilepsy (DRE). In resource-limited countries, lack of epilepsy surgery center is a huge challenge. We presented and illustrated how to create a multidisciplinary protocol with resource-limited settings in a developing country and epilepsy surgery outcome using brain mapping and monitoring techniques for ensuring satisfactory resection. Methods: We created multicentric incomplete but complementary units covering all epilepsy-related sub-specialties and covering a wide geographical area in our country. Then, we conducted a prospective and multicentric study with low resource settings on patients with focal DRE, who underwent resective epilepsy surgery and were followed up for at least 12 months and were evaluated for postoperative seizure outcome and complications if present. Preoperative comprehensive clinical, neurophysiological, neuropsychological, and radiological evaluations were performed by multidisciplinary epilepsy team. Intraoperative brain mapping including awake craniotomy and direct stimulation techniques, neurophysiological monitoring, and electrocorticography was carried out during surgical resection. Results: The study included 47 patients (18 females and 29 males) with mean age 20.4 ± 10.02 years. Twenty-two (46.8%) patients were temporal epilepsy while 25 (53.2%) were extra-temporal epilepsy. The epilepsy surgery outcome at the last follow up was Engel Class I (seizure free) in 35 (74.5%), Class II (almost seizure free) in 8 (17%), Class III (worthwhile improvement) in 3 (6.4%), and Class IV (no worthwhile improvement) in 1 patient (2.1%). Conclusion: With low resource settings and lack of single fully equipped epilepsy center, favorable outcomes after resective surgery in patients with focal DRE could be achieved using careful presurgical multidisciplinary selection, especially with using intraoperative brain mapping and electrocorticography techniques.

Ion-Triggered In Situ Gelling Intranasal Spray of Dronedarone Hydrochloride Nanocarriers: In Vitro Optimization and In Vivo Pharmacokinetic Appraisal.

The current study aims to develop niosomal nanocarriers for intranasal delivery of dronedarone hydrochloride to ameliorate its limited bioavailability. Niosomes were prepared by ethanol injection method and optimized using 3² full factorial experimental design. Both Span® type (X1) and Span®: cholesterol ratio (X2) were set as independent variables. Vesicle size (Y1), polydispersity index (Y2), zeta potential (Y3), and entrapment efficiency (Y4) were set as responses. The optimal formula was further incorporated into an ion-sensitive in situ gelling polymer for intranasal delivery. Optimal formula (N7), which is composed of Span® 80: cholesterol (1:1), was of the least vesicle size (121.27 ± 13.31 nm), least polydispersity index (0.43 ± 0.073), highest zeta potential (-22.23 ± 2.84 mV) and highest entrapment efficiency (73.44 ± 2.8%). About 75.86% and 60.29% of dronedarone hydrochloride were released from N7 dispersion and in situ gel, respectively, within 12 h, compared to only 13.3% released from a drug-free suspension. In vivo pharmacokinetic study on male New Zealand rabbits resulted in significantly higher Cmax, AUC0-72, and AUC0-∞ of intranasal niosomal in situ gel compared to oral suspension. Almost twofold amplification of relative bioavailability was obtained after intranasal administration of niosomal in situ gel (195.7%) compared to oral suspension.

Efficiency of Bacillus thuringiensis and Bacillus cereus against Rhynchophorus ferrugineus.

The Red Palm Weevil (Rhynchophorus ferrugineus (Oliv.) (Coleoptera, Dryophthoridae) is a well-known palm tree pest that has caused enormous economic damage all over the globe. Insecticides are still the primary method of controlling this pest at this period. However, field populations of RPW have been shown to be resistant to pesticides. Using Bacillus spp. might be one of the options for controlling R. ferruginous. In this study, 23 species of Bacillus spp. were isolated from the rhizosphere of date palm trees in Al Ahsa Oasis, Saudi Arabia. The isolates were identified using 16S rRNA gene sequencing. R. ferrugineus larvae and adults were tested on sugarcane pieces that were treated with the B. thuringiensis strain PDC-AHSAA1 and B. cereus strains (PDC-AHSAA2, PDC-AHSA3 and PDC-AHSA4). The LC50 values for larvae and adults were quite low when they were compared with those of the other isolated strains. The B. thuringiensis strain PDC-AHSAA1 was more effective against both the larvae and adults. The determined LC50 values for B. thuringiensis ranged from 4.19 × 107-3.78 × 109. After 21 days, the data on larval mortality and body weight were evaluated. The surviving larvae that were treated with the bacterial isolates did not acquire a substantial weight. For the RPW larvae and adults, the mortality and corrected mortality death rates were increased by increasing the concentration of B. thuringiensis. In conclusion, Bacillus-treated diets negatively influenced the growth and development of the RPW. This research reported on the interaction between the RPW and the rhizosphere Bacillus spp. and highlighted the tremendous potential for the development of microbial resource-based control strategies for this pest.

Construction of sublingual trilaminated Eszopiclone fast dissolving film for the treatment of Insomnia: Formulation, characterization and In vivo clinical comparative pharmacokinetic study in healthy human subjects.

BACKGROUND: Disturbed sleep can cause to m health problems such as cognitive impairment, depressed mood, and negative effects on cardiovascular, endocrine, and immune function. This study formulates and optimizes Eszopiclone trilaminate fast dissolving film. METHODS: Prepared Eszopiclone trilaminate fast dissolving film (Eszopiclone TFDF) was characterized by disintegration time, drug release, tensile strength (TS), percentage elongation (EB%), folding endurance, taste masking test, and in vitro dissolution test. The selected formulas were F2 (0.5% xanthan gum, 10% propylene glycol), F4 (3% sodium alginate, 10% propylene glycol) and F6 (1.5% pullulan, 10% propylene glycol) were subjected to in vivo study compared to conventional Lunesta® tablet. RESULTS: The results indicated that disintegration time was in the range of 940 m. Drug release was found to be in the field of 78.51%-99.99%, while TS values and EB% differed from 11.12 to 25.74 (MPa) and 25.38%-36.43%, respectively. The folding endurance went between 200 and 300 times. All formulas exhibited acceptable uniformity content, surface pH, film thickness, and a good taste feeling. CONCLUSION: F4 had the highest Cmax (39.741 ± 6.785-µg/l) and lower Tmax (1.063 hr) among other formulas and conventional tablets. Therefore, FDFs' technology could increase the therapeutic effect of Eszopiclone.

Feasibility and efficacy of erector spinae plane block versus transversus abdominis plane block in laparoscopic bariatric surgery: a randomized comparative trial.

BACKGROUND: Overweight and obesity are growing public health concerns worldwide. Bariatric surgery is a modality of weight reduction; however, postoperative pain can increase the length of hospital stay, with all the associated consequences. While regional anesthesia is an available option, the feasibility of performing abdominal wall blocks on patients with obesity is questionable. METHODS: Sixty adult patients with a body mass index of 40-50 kg/m2 undergoing laparoscopic bariatric surgery were randomly assigned to receive either an ultrasound-guided transversus abdominis plane (TAP) or erector spinae plane (ESP) block. The primary outcome was the analgesic effect in the first 24 h postoperatively, assessed using the mean visual analog scale (VAS) score. Secondary outcomes were the time required for a successful block, incidence of complications, time to first rescue analgesia, time to flatus or stool passage, and total opioid consumption. RESULTS: The mean VAS score during the first 24 h was higher with the TAP block than with the ESP block (2.78 ± 0.34 vs. 2.32 ± 0.12, P < 0.001). Additionally, the time to first rescue analgesia was greater with the ESP block (P = 0.001) and the time required for a successful block was higher with the TAP block (P = 0.001). However, the incidence of complications, total opioid consumption, and other secondary outcomes was similar between the groups. CONCLUSIONS: Compared with the TAP block, the bilateral ESP block is a more feasible and effective method for intra- and postoperative analgesia in patients undergoing laparoscopic bariatric surgery.

Outcomes of autologous stem cell transplantation for multiple myeloma in Saudi Arabia.

BACKGROUND: In 2015, multiple myeloma (MM) represented 1% of all cancers and about 5% of hematologic malignancies in Saudi cancer registry. We conducted this large study because only small pilot studies have examined MM outcomes after autologous stem-cell transplantation (ASCT). The standard therapy for eligible patients is induction chemotherapy followed by ASCT. OBJECTIVES: Determine the demographic characteristics of MM patients and the outcomes of ASCT. DESIGN: Retrospective. SETTING: Tumor registry database of major tertiary cancer care center in Riyadh. PATIENTS AND METHODS: We identified patients with newly diagnosed MM who underwent ASCT from October 1997 to March 2015. MAIN OUTCOME MEASURES: The demographic characteristics of MM patients and the outcomes of ASCT in the form of response evaluation, progression-free survival (PFS) and overall survival (OS). SAMPLE SIZE: 169 patients with newly diagnosed MM. RESULTS: The median age at diagnosis was 51 years (range 23-69) and 100 (59.2%) were male. The most common immunoglobulin (Ig) subtype was IgG-kappa (80 patients; 47.6%). Most patients presented with advanced ISS stage III (75 patients; 47.5%). The cytogenetic analysis was documented in only 87 patients (51.4%); about half (48.3%) had normal cytogenetics by fluorescence in situ hybridization. Deletion 13 was present in 18.4% of patients. In post-induction therapy, 84 patients (50%) achieved a complete response, which increased to 78.1% (132 patients) after ASCT. The median PFS and OS post-transplantation were 30 and 202 months, respectively. Only one patient (<1%) died in the first 100 days after transplantation. CONCLUSIONS: Our transplant eligible MM patients tend to be younger with a higher OS and a low ASCT-related mortality (<1%) than is reported internationally. LIMITATIONS: Usual limitations of a retrospective analysis using registry-level data; no data on quality of life. CONFLICTS OF INTEREST: None.

Chemical profiling, in vitro antimicrobial and antioxidant activities of pomegranate, orange and banana peel-extracts against pathogenic microorganisms.

BACKGROUND: The use of natural preservatives became of great interest; good examples of these natural preservation agents are plant peels. The use of plant peels has dual benefits; first is their antimicrobial activity against food-borne pathogens, while the second is minimizing agro-industrial wastes. RESULTS: The evaluation of the antimicrobial potential of both methanolic and ethanolic extracts of three fruit peels (orange, pomegranate, and banana), against 4 Gram-positive (G+), 3 Gram-negative bacteria (G-), and 2 fungal strains revealed that both pomegranate peel extracts exhibited significantly higher inhibitory effect on all tested G+ bacteria. Methanolic extract of pomegranate peel gave higher activity than the ethanolic one against G+ and G- bacteria except for S. typhimurium. Against A. flavus and A. niger, both pomegranate and orange extracts showed activity ranging between 65 and 100% more than the positive control. The ethanolic extracts of all tested peels showed a considerable capacity of antioxidant compounds compared to the methanolic extracts. The highest antioxidant capacity was found for ethanolic and methanolic extracts of pomegranate, 66.870 and 56.262 mg/ml, respectively. Generally, the concentration of total phenolic compounds was higher than that of total flavonoids followed by tannins. The highest readings of all tested constituents were reported for pomegranate extracts followed by orange and then banana. The total phenolic content, total flavonoids, and tannins were proportional to antioxidant values. GC-MS of pomegranate peel extracts identified 23 compounds in the methanolic extract versus 31 compounds in the ethanolic one. These components were identified based on their retention times and mass spectral fragmentation pattern. 5-hydroxymethylfufural (HMF) represented the major component in both methanolic and ethanolic extracts with peak area percentage of 65.78% and 48.43%, respectively. CONCLUSIONS: The results showed negative effect of methanolic and ethanolic extracts of pomegranate on G+ and G- bacteria and two fungal pathogenic strains. The phytochemical analysis regarded these results to the high content of phenols, flavonoids, and tannins. GC-MS chromatogram identified many compounds known to be effective as antioxidants and antibacterial and antifungal agents. These indications show that pomegranate peel may be a superior natural food-preserver, but further studies about the suitable formulation, dosage, and possible side-effects are still needed.

Repurposing of Guanabenz acetate by encapsulation into long-circulating nanopolymersomes for treatment of triple-negative breast cancer.

Poor patient response and limited treatment modalities are the major challenges against combating triple-negative breast cancer (TNBC). The high related mortality urges for novel cancer therapeutics. Guanabenz acetate (GA) is an orphan antihypertensive drug with a short half-life. Re-purposing (GA) by developing a polymersome (PS)-based cancer nanomedicine is an innovative approach in treating TNBC. Formulation and optimization of GA-loaded PEGylated Polycaprolactone PS through different process variables (solvent selection, the order of addition, pH of the aqueous phase, and drug to polymer ratio) were achieved by the nanoprecipitation method. The in vitro cellular uptake, anti-cancer, and anti-metastatic activity of GA and GA-loaded PS were tested in MDA-MB 231(TNBC cell line) and MCF-7 cell line. Western blot analysis was performed to elucidate the molecular anti-cancer mechanism. The in vivo biodistribution study and antitumor activity were investigated in the TNBC-xenograft model implanted in mice. Under optimized formulation conditions, GA-loaded PS had a nanosize of 90.5 nm with PDI < 0.2, a zeta potential -9.11 mV, drug encapsulation efficiency of 92.11% and sustained drug release for 6-days. GA-loaded PS exhibited enhanced cellular uptake and achieved a significantly lower IC50 in both breast cancer cell lines compared to free GA. Treatment with GA-loaded PS (60 µM) showed a significant reduction of 60.5 and 78.1% in cancer migration and metastasis in the case of MDA-MB 231 and MCF-7, respectively. Besides, drug-loaded PS increased phosphorylation of translational regulator eIF2α and decreased expression of Rac1 which were essential for decreasing cancer cell survival and metastasis. In vivo biodistribution study of GA-loaded PS showed long-circulating PS with high passively targeted tumor accumulation. Treatment with GA-loaded PS resulted in a significant decrease in tumor size and weight compared to free GA. In conclusion, GA-loaded PS is a new promising cancer therapeutics for the treatment of TNBC.

Formulation and Optimization of Nanospanlastics for Improving the Bioavailability of Green Tea Epigallocatechin Gallate.

The present study aimed to investigate the potential of nanospanlastics for boosting the bioavailability of epigallocatechin gallate (EGCG). EGCG has valuable effects like anti-inflammation, anti-oxidation, and anti-tumorigenesis. Unfortunately, it has a low oral bioavailability due to its limited permeation and poor stability. To overcome these pitfalls, EGCG was fabricated as a nanospanlastic. Nanospanlastics are flexible nanovesicles that are composed of surfactants and edge activators (EAs). EAs improve the deformability of spanlastics by acting as a destabilizing factor of their vesicular membranes. EGCG-loaded spanlastics were prepared by an ethanol injection method, according to 23 factorial design, to explore the impact of different independent variables on entrapment efficiency (EE%), % drug released after 12 h (Q12h), and particle size (PS). In vitro characterization, ex vivo intestinal permeation test, and pharmacokinetic study of the optimized formula were performed. A newly developed RP-HPLC technique was adopted for the estimation of EGCG . The optimized formula (F4) demonstrated more prolonged drug release and a significant improvement in the EE%, permeability, deformability and stability than the corresponding niosomes. The pharmacokinetic study investigated that F4 had a more sustained drug release and a higher bioavailability than the conventional niosomes and free drugs. Nanospanlastics could be a promising approach for improving the bioavailability of EGCG.

Synergistic effect of curcumin and chitosan nanoparticles on nano-hydroxyapatite-induced reproductive toxicity in rats.

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (HAPNPs), a prospective nano-biomaterial, is extensively studied, its interaction on the reproductive system following exposure is less exploited. In the present study, male rats were exposed to HAPNPs (300 mg/kg BW) to determine its possible reproductive toxicity. Also, the protective effects of chitosan (CSNPs, 280 mg/kg BW) and/or curcumin (CurNPs, 15 mg/kg BW) nanoparticles against HAPNPs-induced reproductive toxicity were studied. Animals were orally gavage daily with respective doses for 45 consecutive days. The obtained results indicated that HAPNPs caused a significant decrease in sperm count, sperm motility, testosterone hormone, steroidogenic enzymes (17-ketosteroid reductase and 17ß-hydroxysteroid dehydrogenase), and antioxidant enzymes (glutathione peroxidase, glutathione S-transferase, catalase, and superoxide dismutase) in addition to total antioxidant capacity and reduced glutathione. LH and FSH, abnormal sperm, oxidative stress parameters (thiobarbituric acid-reactive substances (TBARS), nitric oxide (NO), and 8-hydroxy-deoxyguanosine (8-OHdG)), p53, TNFα, and interleukin-6 were significantly increased. The DNA damage was also analyzed by assaying 8-OHdG level which is considered as an indicator of genotoxicity and also suppression of the gene expression of mtTFA, induction of UCP2. Similarly, the histopathological evaluation was also changed following exposure to HAPNPs. The antioxidant activity of CSNPs and CurNPs showed mitigating effect against reproductive deterioration induced by HAPNPs throughout improvements in semen characteristics, sex hormones, inflammatory factors, and antioxidant status. The present study concluded that HAPNPs induced reproductive toxicity and it is important to use nano-antioxidants CSNPs and CurNPs as protective agents.

Formulation, Characterization and Comparative Pharmacokinetic Study of Bupropion Floating Raft System as a Promising Approach for Treating Depression.

The aim of this study was to formulate, evaluate, and compare satiety-enhancing floating raft system (FRS) of bupropion as gastroretentive drug delivery systems (GRDDS) using in-situ gelling pectin and alginate. Bupropion was considered as a good candidate for such systems due to high water solubility that requires frequent dosing. Pectin and alginate could prolong satiety sensation augmenting weight loss of bupropion. A 24 full factorial design was tailored to inspect the effect of the response variables (gel-forming polymer type, calcium carbonate percentage, glyceride lipid type and percentage). Gelation lag time, floating lag time, as well as drug released percent after 1 and 8 h were selected as dependent variables. The optimal system was investigated for compatibility and bioavailability study in healthy human volunteers relative to marketed Wellbutrin® sustained release tablets. The optimal FRS (3% alginate, 2% precirol®, and 2% CaCO3) was selected. This system had an optimum viscosity that will allow a rapid sol-gel transformation in the stomach, excellent floating behavior, and controlled release profile with a comparable bioavailability. The optimal FRS would be a novel liquid GRDDS in controlling bupropion rate release especially for depression associated with eating disorders or dysphagia improving patient compliance and drug efficacy.

Penicillin-binding proteins regulate multiple steps in the polarized cell division process of Chlamydia.

Chlamydia trachomatis serovar L2 and Chlamydia muridarum, which do not express FtsZ, undergo polarized cell division. During division, peptidoglycan assembles at the pole of dividing Chlamydia trachomatis cells where daughter cell formation occurs, and peptidoglycan regulates at least two distinct steps in the polarized division of Chlamydia trachomatis and Chlamydia muridarum. Cells treated with inhibitors that prevent peptidoglycan synthesis or peptidoglycan crosslinking by penicillin-binding protein 2 (PBP2) are unable to initiate polarized division, while cells treated with inhibitors that prevent peptidoglycan crosslinking by penicillin-binding protein 3 (PBP3/FtsI) initiate polarized division, but the process arrests at an early stage of daughter cell growth. Consistent with their distinct roles in polarized division, peptidoglycan organization is different in cells treated with PBP2 and PBP3-specific inhibitors. Our analyses indicate that the sequential action of PBP2 and PBP3 drives changes in peptidoglycan organization that are essential for the polarized division of these obligate intracellular bacteria. Furthermore, the roles we have characterized for PBP2 and PBP3 in regulating specific steps in chlamydial cell division have not been described in other bacteria.

Role of Endoscopic Stent Insertion on Management of Gastric Twist after Sleeve Gastrectomy.

PURPOSE: The effectiveness of endoscopic management of twisting of the gastric pouch after sleeve gastrectomy. METHODS: This was a retrospective study on Ain Shams University Hospital. Patients who had obstructive symptoms and diagnosed with twist after gastric sleeve were included in this study. RESULTS: From May 2017 to January 2019, 860 patients underwent LSG as a definitive procedure. Thirty-two (3.7%) patients developed symptoms of gastric obstruction. Twenty-two (2.5%) patients diagnosed with sleeve axial twist were included in this study after excluding 11 patients with sleeve stricture. A total of 72% (16 out of 22) of patients were female, with a mean age of 41. The mean time of presentation was 40 days (20-60 days) after surgery. Gastrografin contrast study was positive in 14 (63%) patients. 3D contrast CT was positive in 100% of cases. The timing of endoscopic intervention was 40 ± 20 days (20-60) after surgery. Endoscopic treatment was successful in 20 patients (91%). Recovery was uneventful in 19 patients; 1 patient had esophageal stricture at the upper end of the stent, which necessitated a session of dilation. The success of endoscopic intervention was 91% with complete relief of symptoms and correction of the gastric pouch axis. Endoscopic intervention failed in only 2 patients (9%) who necessitated laparoscopic exploration after stent removal. CONCLUSION: Gastric pouch twisting is a rare complication; however, it has a rising incidence. Endoscopic stent insertion is highly effective on the management of twisting after SG and it should be tried before any further surgical intervention.

Proniosomal Telmisartan Tablets: Formulation, in vitro Evaluation and in vivo Comparative Pharmacokinetic Study in Rabbits.

OBJECTIVE: The purpose of this study was to prepare proniosomal vesicles of Telmisartan (TEL) to be compressed into tablets which will be further evaluated in vitro and in vivo. MATERIALS AND METHODS: An experimental design was adopted using surfactants of different HLB values (span 40-brij 35), different cholesterol ratios (20-50%) and different phospholipid types (egg yolk-soyabean). Different responses were measured followed by tablet manufacturing. The highest EE was shown in F3 (85%) while the lowest value was obtained in F7 (8.4%). Finally, zeta potential results were in the range of -0.67 to -27.6 mv. Compressibility percent revealed that F5 showed an excellent flowability characteristic with a value of 9.74±1.61 while F3 and F6 showed good flowability characteristics. By the end of the release, F6 showed approximately 90% drug release. RESULTS: F6 was selected for the in vivo study; Cmax was increased by 1.5-fold while AUC0-∞ also increased significantly by 3-fold when compared with commercial tablet and finally, tmax was increased by 3-fold indicating sustained release pattern. The relative bioavailability was also increased by 3.2-fold. CONCLUSION: The results of this study suggested that the formulation of compressed tablets containing more stable proniosomal powder extended the release of TEL and increased its bioavailability as well.

Therapeutic potential of human umbilical cord derived mesenchymal stem cells on rat model of liver fibrosis.

End-stage liver disease is a worldwide cause of morbidity and mortality, which is associated with a considerable economic burden. As the disease progresses, fibrosis will replace the hepatic architecture and compromise liver functions. The regenerative approach for the injured liver can provide a hope for these patients; however, it is still facing many challenges. In the current study, we aimed at (1) assessing hepatic regenerative capacity of mesenchymal stem cells, isolated from human umbilical cord blood (HMSCs), in a rat model of carbon-tetrachloride (CCL4) induced liver fibrosis, (2) comparing the therapeutic effects with other cell populations derived from umbilical cord blood and (3) evaluating the host response to the human-derived cells. Fifteen rats received either the whole mononuclear cell fraction (HMNCs), CD34-ve subpopulation or HMSCs. A fourth group did not receive any treatment and another group was left without induction of fibrosis as positive and negative controls. All groups that received cellular treatment showed homing of the human cells and improvement of the liver architecture and functional capacity. The groups received CD34-ve cells and HMSCs had the most efficient improvement in liver functions, microscopic regenerative markers and histological appearance while the least immune reaction was noted with HMSCs. HUCB-MSCs showed significant immunemodulatory effect on rat immune cells. This study can provide a clue about a simple and effective method for the management of fibrotic liver diseases.