Kaposi varicelliform eruption: an unusual presentation caused by varicella zoster virus in a healthy adult patient - a case report.

BACKGROUND: Kaposi Varicelliform Eruptions (KVE), also known as eczema herpeticum, is a rare and potentially life-threatening dermatological condition primarily attributed to herpes simplex virus (HSV) infection, with less frequent involvement of Coxsackie A16, vaccinia, Varicella Zoster, and smallpox viruses. Typically associated with pre-existing skin diseases, especially atopic dermatitis, KVE predominantly affects children but can manifest in healthy adults. Characterized by painful clusters of vesicles and sores on the skin and mucous membranes, it often masquerades as other dermatological disorders. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain relief and inflammation, though their potential role as KVE triggers remains uncertain. CASE REPORT: Here, we present a case of an 18-year-old female with KVE attributed to Varicella Zoster virus (VZV) and successfully treated with oral acyclovir within a week, underscoring the significance of early recognition and intervention. KVE can manifest with systemic symptoms like fever, fatigue, and lymphadenopathy and may involve multiple organ systems, necessitating possible antibiotic use for complications. CONCLUSION: This case underscores the importance of prompt KVE identification and consideration of antiviral therapy to enhance patient outcomes. Further research is warranted to elucidate predisposing factors for this rare condition.

Modulation of autophagy, apoptosis and oxidative stress: a clue for repurposing metformin in photoaging.

Long-term sun exposure is the commonest cause of photoaging, where mutual interplay between autophagy, oxidative stress, and apoptosis is incriminated. In combating photoaging, pharmacological approaches targeted to modulate autophagy are currently gaining more ground. This study aimed to examine repurposing metformin use in such context with or without the antioxidant coenzyme Q10 (coQ10) in ultraviolet A (UVA) irradiation-induced skin damage. The study was conducted on 70 female CD1 mice that were randomly assigned into seven groups (10/group): normal control, vehicle-treated-UVA-exposed mice, three metformin UVA-exposed groups (Topical 1 and 10%, and oral 300 mg/kg), topical coQ10 (1%)-treated mice, and combined oral metformin with topical coQ10-treated UVA-exposed mice. After UVA-exposure for 10 weeks (3 times/week), macroscopic signs of photoaging were evaluated. Mice were then euthanized, and the skin was harvested for biochemical estimation of markers for oxidative stress, inflammation, matrix breakdown, and lysosomal function. Histopathological signs of photoaging were also evaluated with immunohistochemical detection of associated changes in autophagic and apoptotic markers. Metformin, mainly by topical application, improved clinical and histologic signs of photoaging. This was associated with suppression of the elevated oxidative stress, IL-6, matrix metalloproteinase 1, and caspase, with induction of cathepsin D and subsequent change in anti-LC3 and P62 staining in skin tissue. In addition to metformin antioxidant, anti-inflammatory, and antiapoptotic activities, its anti-photoaging effect is mainly attributed to enhancing autophagic flux by inducing cathepsin D. Its protective effect is boosted by coQ10, which supports their potential use in photoaging.

Value of early second session shock wave lithotripsy in treatment of upper ureteric stones compared to laser ureteroscopy.

PURPOSE: The safety and efficacy of early second session shock wave lithotripsy (SWL) compared with laser ureteroscopy (URS) for the treatment of upper ureteric stones were evaluated. METHODS: From January to October 2019, 108 patients with upper ureteric stones (< 1.5 cm and ≤ 1000 Hounsfield unit (HU)) were randomized into SWL and laser URS groups. The second SWL session was performed within 48-72 h of the first session. Using plain abdominal X-ray and ultrasonography, patients were evaluated 48-72 h after the first SWL session and one week after the second and third SWL sessions or one week after URS. The procedure was considered a success when no additional procedures were needed to clear the stone. To determine the stone-free rate (SFR), noncontrast computed tomography of the urinary tract was performed three months postoperatively. RESULTS: In the SWL group, the success rates were 92.6% and 94.4% after the second and third sessions. The SFR was 96.2% in the laser URS group. The success rates were not significantly different between the second and third SWL sessions versus the laser URS (p = 0.418 and 0.660, respectively). Operative and fluoroscopy times were significantly longer in the SWL group (p = 0.001), and JJ stent insertions were needed after laser URS. CONCLUSION: Ultraslow full-power SWL treatment of patients with upper ureteric stones (< 1.5 cm and ≤ 1000 HU) with an early second session is safe and effective compared to laser URS. Patients who do not respond to early second SWL session should be shifted to another treatment modality.

Ultraslow full-power shock wave lithotripsy protocol in the management of high attenuation value upper ureteric stones: A randomized comparative study.

OBJECTIVES: To evaluate the efficacy and safety of ultraslow full-power shock wave lithotripsy protocol in the management of high attenuation value upper ureteric stones compared with slow-rate, power-ramping shock wave lithotripsy. METHODS: This was a randomized trial enrolling patients with a single high attenuation value (≥1000 HU) upper ureteric stones between January 2019 and July 2019. Ultraslow full-power shock wave lithotripsy (54 patients) was applied at a rate of 30 shock waves/min with power ramping from 6 to 18 kV for 100 shock waves, then a safety pause for 2 min, followed by ramping 18-22 kV for 100 shock waves, then a safety pause for 2 min. Then, full power (22 kV) was maintained until the end of the session. Slow-rate, power-ramping shock wave lithotripsy (47 patients) was applied at a rate of 60 shock waves/min with power ramping from 6 to 10 kV during the first 500 shock waves, then from 11 to 22 kV during the next 1000 shock waves, then maintained on 22 kV in the last 1500 shock waves. Up to three sessions were carried out with a follow up 3 months after the last session. The primary outcome was the stone-free rate. Perioperative data of the two protocols were compared. RESULTS: There was no significant difference in preoperative data. The stone-free rate was significantly higher in ultraslow full-power shock wave lithotripsy after single (92.6% vs 23.4%) and multiple (96.3% vs 63.8%) sessions. Most complications were mild, with no significant difference between both groups (9.3% vs 12.8%; P = 0.573). Logistic regression analysis identified ultraslow full-power shock wave lithotripsy protocol as the only significant independent factor for the stone-free rate (odds ratio 12.589, P = 0.025). CONCLUSION: Ultraslow full-power shock wave lithotripsy for high attenuation value upper ureteric stones is associated with a significantly higher stone-free rate, and with mild complications that are comparable to those of standard shock wave lithotripsy.

Development of tizanidine loaded aspasomes as transdermal delivery system: ex-vivo and in-vivo evaluation.

New generation of amphiphilic vesicles known as aspasomes were investigated as potential carriers for transdermal delivery of tizanidine (TZN). Using full factorial design, an optimal formulation was developed by evaluating the effects of selected variables on the properties of the vesicles with regards to entrapment efficiency, vesicle size and cumulative percentage released. The optimal formula (TZN-AS 6) consisting of 20 mg TZN, 50 mg ascorbyl palmitate (AP), 50 mg cholesterol (CH) and 50 mg Span 60, represented well dispersed spherical vesicles in the nanorange sizes and exhibited excellent stability under different storage conditions. Ex-vivo permeation studies using excised rat skin showed a 4.4-fold increase of the steady state flux in comparison to the unformulated drug (p < 0.05). The pharmacokinetic parameters obtained from the in-vivo study using Wistar rats, showed that the bioavailability of TZN was enhanced significantly (p < 0.05) when compared to the oral market product of TZN, Sirdalud®. Moreover, skin irritancy tests confirmed that the vesicles were non-invasive and safe for the skin. Based on the results obtained, the optimised aspasomes formula represents a promising Nano platform for TZN to be administered transdermally, thus improving the therapeutic efficacy of this important muscle relaxant.

Percutaneous nephrostomy versus JJ ureteric stent as the initial drainage method in kidney stone patients presenting with acute kidney injury: A prospective randomized study.

OBJECTIVE: To compare percutaneous nephrostomy tube versus JJ stent as an initial urinary drainage procedure in kidney stone patients presenting with acute kidney injury. METHODS: Between January 2017 and January 2019, 143 patients with acute kidney injury secondary to obstructive kidney stone were prospectively randomized into the percutaneous nephrostomy tube group (71 patients) and JJ stent group (72 patients) at Beni-Suef University Hospital, Beni-Suef, Egypt. Exclusion criteria included candidates for acute dialysis, fever (>38°C), pyonephrosis, pregnancy and uncontrolled coagulopathy. The period required for serum creatinine normalization, failure of insertion, operative and fluoroscopy time were recorded. Definitive stone management for proximal ureteral stones >1.5 cm consisted of percutaneous nephrolithotomy for the percutaneous nephrostomy group and ureteroscopic laser lithotripsy for the JJ stent group. For stone size <1.5 cm, ureteroscopy or shockwave lithotripsy was carried out for both groups. Percutaneous nephrolithotomy was carried out for renal stones >2 cm, and shockwave lithotripsy for stones <2 cm. Distal and mid ureteral stones were treated by ureteroscopy. RESULTS: The percutaneous nephrostomy group had shorter operative time (P = 0.001). There was no significant difference in the recovery period for normalization of serum creatinine between both groups (P = 0.120). Procedural failure, ureteric mucosal injury and perforations increased in the case of male sex, stone size >1.5 cm and upper ureteric stones in the JJ stent group. Procedural failure, pelvic perforations and intraoperative bleeding increased in case of male sex, mild hydronephrosis and stone size >2.5 cm in the percutaneous nephrostomy group. Suprapubic pain, urethral pain and lower urinary tract symptoms were significant in the JJ stent group. The presence of a JJ stent directed us toward ureteroscopy (P = 0.002) and the presence of a percutaneous nephrostomy directed us toward percutaneous nephrolithotomy (P = 0.001). CONCLUSIONS: Percutaneous nephrostomy facilitates subsequent percutaneous nephrolithotomy, especially when carried out by a urologist, and it has a higher insertion success rate, a shorter operative time and a lesser incidence of postoperative urinary tract infection than a JJ stent. A JJ stent facilitates subsequent ureteroscopy, but operative complications can increase in the case of proximal ureteral stones >1.5 cm.

Ultraslow full-power shock wave lithotripsy versus slow power-ramping shock wave lithotripsy in stones with high attenuation value: A randomized comparative study.

OBJECTIVES: To compare the efficacy and safety of ultraslow full-power versus slow rate, power-ramping shock wave lithotripsy in the management of stones with a high attenuation value. METHODS: This was a randomized comparative study enrolling patients with single high attenuation value (≥1000 Hounsfield unit) stones (≤3 cm) between September 2015 and May 2018. Patients with skin-to-stone distance >11 cm or body mass index >30 kg/m2 were excluded. Electrohydraulic shock wave lithotripsy was carried out at rate of 30 shock waves/min for group A versus 60 shock waves/min for group B. In group A, power ramping was from 6 to 18 kV for 100 shock waves, then a safety pause for 2 min, followed by ramping 18-22 kV for 100 shock waves, then a safety pause for 2 min. This full power (22 kV) was maintained until the end of the session. In group B, power ramping was carried out with an increase of 4 kV each 500 shock waves, then maintained on 22 kV in the last 1000-1500 shock waves. Follow up was carried out up to 3 months after the last session. Perioperative data were compared, including the stone free rate (as a primary outcome) and complications (secondary outcome). Predicting factors for success were analyzed using logistic regression. RESULTS: A total of 100 patients in group A and 96 patients in group B were included. The stone-free rate was significantly higher in group A (76% vs 38.5%; P < 0.001). Both groups were comparable in complication rates (20% vs 19.8%; P = 0.971). The stone-free rate remained significantly higher in group A in logistic regression analysis (odds ratio 24.011, 95% confidence interval 8.29-69.54; P < 0.001). CONCLUSIONS: Ultraslow full-power shock wave lithotripsy for high attenuation value stones is associated with an improved stone-free rate without affecting safety. Further validation studies are required using other shock wave lithotripsy machines.

Outcome of Botulinum Toxin-A intraprostatic injection for benign prostatic hyperplasia induced lower urinary tract symptoms: A prospective multicenter study.

INTRODUCTION: Our aim was to determine the factors predicting the outcome of intraprostatic injection of Botulinum Toxin-A (BTX-A) in the treatment of benign prostatic hyperplasia (BPH)-induced lower urinary tract symptoms (LUTS) and to evaluate its efficacy and safety. METHODS: Between September 2016 and May 2018, 45 Egyptian patients, with BPH-induced LUTS were included; the indication was a failure of medical treatment, unfit, or refusing surgical intervention. Measurements of prostate size by TRUS, total PSA level before and 12 weeks after injection. IPSS, uroflow, and postvoiding residual urine (PVR) were measured before injection, 2, 4, 8 and 12 weeks postinjection. 100 U BTX-A vial was diluted with 10 mL of saline then injected into the transition zone at base and midzone of the prostate by TRUS. RESULTS: The mean patients' age was 64.4 ± 6.6 years. Mean baseline IPSS 24.06 decreased to 18.75 at 2 weeks and progressively decreased to 16.37 at 12 weeks (P < 0.001), Q max of 9.08 mL/s. increased to 10.44 at 2 weeks and 11.44 at 12 weeks (P < 0.001), mean prostate volume was 67.44cc; decreased to 66.06cc (P < 0.001) at 12 weeks and mean residual urine was 82.62 mL and decreased to 57.66 mL at 12 weeks. DISCUSSION: Intraprostatic injection of BTX-A as modality treatment of LUTS/BPH significantly improve IPSS, Q max , PVR, and decrease prostate volume. We can suspect better results with this line of treatment in patients with IPSS ≤ 22 and Q max ≤ 10 mL/min and prostate volume ≤ 56.5cc.

Evaluation of bilosomes as nanocarriers for transdermal delivery of tizanidine hydrochloride: in vitro and ex vivo optimization.

Bilosomes were developed in order to investigate their efficacy as nanocarriers for transdermal delivery of Tizanidine HCl (TZN), a skeletal muscle relaxant with low oral bioavailability. Full factorial experimental design consisting of 27 combinations was generated to study the effects of surfactant type, surfactant-to-cholesterol ratio and the amount of bile salt on the entrapment efficiency (EE), the vesicle size (VS) and in vitro dissolution of the TZN-loaded bilosomes. The permeation through the stratum cornea was optimized with the vertical diffusion assembly using excised rat skin. The permeation parameters of the selected bilosomes were compared to the unformulated drug and it was shown that TZN-B24 exhibited the highest enhancement ratio (ER = 8.8).The optimal formula (TZN-B24) consisting of span 60 in a ratio with cholesterol of 1:1 and 20 mg of bile salt was obtained by employing the desirability function of Design-Expert® software. The mathematical model used for the optimization was validated by comparing the predicted values of the EE (82.3%) and the VS (165.8 nm) with the experimental values of EE = 84.42% and of VS = 161.95 nm. TZN-B24 displayed high zeta potential which contributed to its good stability. It was evident from the results of this study that incorporating TZN in bilosomes improved significantly its permeation through the skin barrier and thus bilosomes can offer a potential nanoplatform using the transdermal route to improve the bioavailability of the drug.

Randomized, double-blind, placebo-controlled trial to compare solifenacin versus trospium chloride in the relief of double-J stent-related symptoms.

PURPOSE: We aimed to compare the safety and efficacy of solifenacin versus trospium chloride and compare each drug versus placebo regarding the relief of stent-related symptoms following uncomplicated ureteroscopic lithotripsy (URSL). METHODS: In a prospective, randomized, double-blind study, 210 eligible patients who underwent URSL with double-J stent insertion were recruited and randomly assigned to either the first group, receiving solifenacin (10 mg), second group, receiving trospium chloride (60 mg), or the third group, receiving placebo (one tablet). All patients were kept on study medication once daily during the entire 2-week postoperative period. All subjects were asked to complete a brief-form questionnaire to assess the lower urinary symptoms, stent-related body pain and hematuria, preoperatively and 2 weeks postoperatively. RESULTS: There were no statistically significant differences among the study groups in terms of mean age, gender, anthropometric measurements, stone and stent criteria. The overall symptom score, urgency, urge incontinence, flank pain, urethral pain and gross hematuria scores were significantly lower in solifenacin group compared to trospium chloride and placebo groups (p < 0.001). Concerning frequency and nocturia, there was no significant difference in mean scores across all groups. Drug-related side effects, particularly constipation, were higher in trospium group than in solifenacin one. CONCLUSIONS: Solifenacin treatment showed significant improvement in almost all domains of stent-related symptoms than trospium. In terms of safety and tolerance, both drugs were comparable. Future studies should be designed to address the impact of combined drugs and lower doses in the management of DJ stent-related symptoms.

Mucoadhesive niosomal in situ gel for ocular tissue targeting: in vitro and in vivo evaluation of lomefloxacin hydrochloride.

Eradication of ophthalmic infections depends on increasing transcorneal permeation and localizing antibiotics at ocular surface. This study aimed at formulating lomefloxacin HCl (LF) in the form of niosomes and evaluating the in vivo performance of best formula in rabbits' eyes. Vesicles were developed by mixing three surfactants at three molar ratios of 1:1, 1:2 and 1:3 of surfactant to cholesterol. Size, zeta potential, release percentage, transcorneal permeation parameters, stability studies, cytotoxicity and antibacterial activity of niosomes were determined. Niosomes showed encapsulation efficiency of more than 78%, particle size below 500 nm and zeta potential below -43.6. The produced vesicles showed significantly higher amounts of drug permeated across cornea (166%) compared to LF solution. The in vivo study showed 2-5 folds increase in drug concentration in ocular fluids and tissues following administration of niosomes compared to marketed formula (from 3.75 to 10.31 mcg/mL in the cornea). Microbiological studies showed 35 folds increase in the antibacterial activity of LF niosomes compared to free drug; where MBC decreased from 31.25 mcg/mL in case of LF solution to 0.97 mcg/mL for niosomal gel. The formulated niosomes enhanced the ocular bioavailability of LF through increasing transcorneal permeation and localizing drug at site of action.

Pharmaceutical and pharmacokinetic evaluation of a novel fast dissolving film formulation of flupentixol dihydrochloride.

The objective of the present study was to develop fast dissolving oral film of the antipsychotic drug, flupentixol dihydrochloride, to enhance its bioavailability, optimize its therapeutic effect when used to treat depression with anxiety, and increase the convenience and compliance by the mentally ill, developmentally disable, elderly, and pediatric patients. Six formulae were prepared with different concentrations of water-soluble polymers vis. hydroxypropyl methylcellulose (HPMC E5) and carboxymethyl cellulose (CMC) by solvent casting technique. The prepared films were subjected to characterization for folding endurance, weight variations, thickness, disintegration time, drug release pattern, and drug content. Physical compatibility between the drug and excipients was guaranteed in the selected formulation (2% HPMC) by means of differential scanning calorimetry analysis and Fourier-transform infrared spectroscopy. This formulation revealed high stability after testing according to the International Conference on Harmonisation guidelines. In vivo studies based on single phase parallel design were carried out for the optimized formulation in healthy human volunteers. The concentration of flupentixol dihydrochloride in plasma samples was analyzed by a developed validated LC-MS/MS assay method and the pharmacokinetic parameters of the established formulation were compared with the commercially available oral tablets. Faster rate of absorption of flupentixol could be obtained from the oral film formulation and the relative bioavailability was found to be 151.06% compared to the marketed product.

The effect of immediate neoadjuvant electromotive instillation of mitomycin C with Bacillus Calmette-Guérin versus BCG alone in non-muscle-invasive bladder cancer: A randomized controlled trial.

PURPOSE: The clinical effect of neoadjuvant intravesical instillation of chemotherapy immediately before transurethral resection of bladder tumors (TURBT) has been a subject of recent research. The aim of this study was to assess the effect of immediate neoadjuvant electromotive instillation of mitomycin C before transurethral resection for patients with non-muscle-invasive urothelial bladder cancer. MATERIALS AND METHODS: Our study was a randomized clinical trial carried out on 50 patients diagnosed with non-muscle-invasive urothelial bladder cancer. Patients were classified into two groups: Group I consisted of 25 patients who received neoadjuvant electromotive drug administration of mitomycin C before TURBT and intravesical bacille Calmette-Guerin (BCG) per week for 6 weeks; Group II consisted of 25 patients who were treated with TURBT followed by intravesical BCG per week for 6 weeks alone (standard of care). Patients were followed up at 3, 6, 12, and 18 months by cystoscopy. RESULTS: Patients who received neoadjuvant electromotive drug administration of mitomycin C before TURBT in combination with BCG had a low recurrence rate compared with those who received BCG alone (12.0% vs. 48.0%, respectively; p=0.012) and a longer disease-free interval (88.0% vs. 52.0%, respectively; p=0.012). Four patients developed progression to muscle-invasive disease (16.0%) in the BCG alone group. However, this difference was not statistically significant (p=0.516). Regarding adverse effects, there were no statistically significant differences between the groups. CONCLUSIONS: Neoadjuvant intravesical electromotive drug administration of mitomycin C before TURBT is safe; reduces recurrence rates and enhances the disease-free interval compared with TURBT followed by BCG alone.

Liver targeting of ledipasvir via galactosylated chitosan-coated spanlastics: chemical synthesis, statistical optimization, in vitro, and pharmacokinetic evaluation.

INTRODUCTION: Ledipasvir is an effective direct acting antiviral agent used in the treatment of hepatitis C virus. The high price of ledipasvir was a reason for its limited provision to wide population of HCV patients. OBJECTIVES: Our objective is the formulation of liver targeted drug delivery system that can increase the amount of ledipasvir delivered to liver and prolong its liver residence in an attempt to reduce its recommended dose and its costing in the treatment of HCV. METHODS: Different ledipasvir-loaded spanlastic formulations were prepared using the ethanol injection method and evaluated with respect to the particle size, zeta potential, polydispersity index, and entrapment efficiency %. Using Design-Expert ® software, the optimum spanlastics formulation was selected; then, it was coated by synthesized galactosylated chitosan. A pharmacokinetic study was carried out to evaluate the ability of the prepared galactosylated chitosan-coated spanlastics formulation to enhance ledipasvir liver bioavailability when it was administrated via the oral route. RESULTS: The pharmacokinetic study revealed that the optimized galactosylated chitosan-coated spanlastics exhibited significantly higher liver peak concentration (Cmax) and area under liver concentration versus time curve (AUC0-72 h) and significant prolongation in the liver terminal half life (t½) and mean residence time (MRT) compared to the free ledipasvir dispersion with values of 6270 ng/g, 61,706.3 ng.h/g, 15.85 h, and 24.66 h, respectively. CONCLUSIONS: Enhanced liver bioavailability of ledipasvir has been accomplished using the developed galactosylated chitosan-coated spanlastics which can be a base for probable reduction in the required dose of ledipasvir in HCV treatment.

The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial.

AIM: The role of surgical castration and rosuvastatin treatment on lipid profile and lipid metabolism related markers was evaluated for their prognostic significance in metastatic prostate cancer (mPC) patients. METHODS: A total of 84 newly diagnosed castrated mPC patients treated with castration were recruited and divided into two groups: Group I served as control (statin non-users) while group II treated with Rosuvastatin (20 mg/day) for 6 months and served as statin users. Prostate specific antigen (PSA), epidermal growth factor receptor (EGFR), Caveolin-1 (CAV1), lipid profile (LDL, HDL, triglycerides (TG) and total cholesterol (TC)) and lipid metabolism related markers (aldoketoreductase (AKR1C4), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter A1 (ABCA1), and soluble low density lipoprotein receptor related protein 1 (SLDLRP1)) were measured at baseline, after 3 and 6 months. Overall survival (OS) was analyzed by Kaplan-Meier and COX regression for prognostic significance. RESULTS: Before castration, HMG-CoA reductase was elevated in patients <65 years (P = 0.009). Bone metastasis was associated with high PSA level (P = 0.013), but low HMGCR (P = 0.004). Patients with positive family history for prostate cancer showed high levels of EGFR, TG, TC, LDL, alkaline phosphatase (ALP), but low AKR1C4, SLDLRP1, CAV1 and ABCA-1 levels. Smokers had high CAV1 level (P = 0.017). After 6 months of castration and rosuvastatin administration, PSA, TG, LDL and TC were significantly reduced, while AKR1C4, HMGCR, SLDLRP1, CAV1 and ABCA-1 were significantly increased. Overall survival was reduced in patients with high baseline of SLDLRP1 (>3385 pg/ml, P = 0.001), PSA (>40 ng/ml, P = 0.003) and CAV1 (>4955 pg/ml, P = 0.021). CONCLUSION: Results of the current study suggest that the peripheral lipidogenic effects of rosuvastatin may have an impact on the treatment outcome and survival of castrated mPC patients. TRAIL REGISTRATION: This trial was registered at the Pan African Clinical Trial Registry with identification number PACTR202102664354163 and at ClinicalTrials.gov with identification number NCT04776889.

Niosomes as a potential drug delivery system for increasing the efficacy and safety of nystatin.

Nonionic surfactant (NIS) vesicles (niosomes) formed from self-assembly of hydrated synthetic NIS monomers are capable of entrapping a variety of drugs and have been evaluated as an alternative to liposomes. Nystatin (NYS) is a polyene antifungal drug that has been used in the treatment of cutaneous, vaginal and oral fungal infections since the 1950s. The aim of this work is to encapsulate NYS in niosomes to obtain a safe and effective formula administered parenterally for neutropenic patients. NYS niosomes were prepared by the thin-film hydration method using Span 60 or Span 40 and cholesterol (CHOL). Stearylamine and dicetyl phosphate were added as the positive and negative charge-inducing agents (CIA), respectively. Two molar ratios were used, namely NIS/CHOL/CIA (1:1:0.1 and 2:1:0.25). Neutral and positively charged niosomes gave the highest encapsulation efficiencies. NYS niosomes were characterized using transmission electron microscopy, differential scanning calorimetry and dynamic light scattering. The release of neutral and negatively charged NYS niosomes was estimated, and it showed a slow sustained release profile. A 25-kGy γ-irradiation dose was sufficient to sterilize the investigated vesicles. NYS niosomes exerted less nephrotoxicity and hepatotoxicity in vivo, showed higher level of drug in vital organs and revealed pronounced efficacy in elimination of the fungal burden in experimental animals infected with Candida albicans compared with those treated with free NYS. Niosomal encapsulation thus provided means for parenteral administration of NYS, reducing its toxicity and making it a more active antifungal agent.

Niosomal encapsulation of the antitubercular drug, pyrazinamide.

It is estimated that more than one-third of the world population is infected with Mycobacterium tuberculosis. Pyrazinamide (PZA) plays a unique role in shortening therapy because it kills a population of semilatent tubercle bacilli residing in an acidic environment. Niosomes are vesicles made up of non-ionic surfactant and exhibit behavior similar to liposomes in vivo. Preparation of PZA niosomes took place using different molar ratios of Span 60 and Span 85, with cholesterol (CH) i.e. Span: CH (1:1) and (4:2). Dicetyl phosphate and stearyl amine were used in preparation of negative and positively charged niosomes, respectively. Free PZA was separated by cooling centrifugation and estimated spectrophotometrically at 268.4 nm. Niosomes were characterized by electron microscopy and differential scanning calorimetry. The highest percentage PZA entrapped was obtained using Span 60 and the molar ratio (4:2:1) negatively charged niosomes. This was followed by the neutral PZA neutral (4:2) Span 60 niosomes. Biological evaluation of selected PZA niosomal formulations took place on guinea pigs infected with M. tuberculosis. The present work is an attempt to target maximum concentration of PZA to the affected site (lungs) and to exclude undesirable side effects and decrease toxicity. Macrophage targeting and overcoming drug resistance is our final goal.

Galactosylated Chitosan Coated Liposomes of Ledipasvir for Liver Targeting: Chemical Synthesis, Statistical Optimization, In-vitro and In-vivo evaluation.

Ledipasvir is a novel antiviral agent used in the treatment of hepatitis C. We aim in our study to increase its delivery to hepatocytes and prolong its retention within liver. Several formulae of ledipasvir loaded liposomes were prepared and the best formula regarding particle size, zeta potential, polydispersity index and entrapment efficiency was selected. On the other hand, galactosylated chitosan was synthesized in a chemical reaction. Then the best liposomes formula was coated with the galactosylated chitosan. Having galactose residues on their surface, the coated liposomes can bind to the asialoglycoprotein receptors on the targeted hepatocytes enhancing ledipasvir uptake into them. The galactosylated chitosan coated liposomes had particle size of 218.2 nm ± 7.21, zeta potential of 27.15 mV ± 1.76, polydispersity index of 0.278 ± 0.055 and entrapment efficiency % of 54.63% ± 0.05 respectively. The pharmacokinetic study revealed a significant increase in the liver peak concentration (Cmax) and the area under liver concentration versus time curve AUC(0-72 h) and significant prolongation in the liver terminal half life (t½) and mean residence time (MRT) in comparison to the oral dispersion of ledipasvir with values of 11,400 ng/g, 88,855 ng∗h/g, 32.00 h and 18.11 h respectively.

Randomized Controlled Trial of Laparoscopic versus Open Radical Cystectomy in a Laparoscopic Naïve Center.

BACKGROUND: Laparoscopic radical cystectomy is a challenging surgical procedure; however, it has been largely abandoned in favor of the more intuitive robotic-assisted cystectomy. Due to the prohibitive cost of robotic surgery, the adoption of laparoscopic cystectomy is of relevance in low-resource institutes. Methodology. This is a randomized controlled trial comparing laparoscopic radical cystectomy (LRC) to open radical cystectomy (ORC) at a single institute. Each group included thirty patients. The trial was designed to compare both approaches regarding operative time, blood loss, transfusion requirements, length of hospital stay, time to oral intake, requirement of opioid analgesia, and complications. RESULTS: LRC was associated with less hospital stay (9.8 vs. 13.8 days, P=0.001), less time to oral solid intake (6 vs. 8.6 days, P=0.031), and lower opioid requirements (23.3% vs. 53.3%, P=0.033). There was a trend towards lower blood loss and transfusion requirements, but this did not reach statistical significance. Overall complication rates were comparable. CONCLUSION: Laparoscopic radical cystectomy was associated with comparable postoperative outcomes when compared to ORC in the first laparoscopic cystectomy experience in our center. Benefitting from the assistance of an experienced laparoscopic surgeon is recommended to shorten the learning curve.

Floating tablet of trimetazidine dihydrochloride: an approach for extended release with zero-order kinetics.

Trimetazidine dihydrochloride is an effective anti-anginal agent; however, it is freely soluble in water and suffers from a relatively short half-life. To solve this encumbrance, it is a prospective candidate for fabricating trimetazidine extended-release formulations. Trimetazidine extended-release floating tablets were prepared using different hydrophilic matrix forming polymers including HPMC 4000 cps, carbopol 971P, polycarbophil, and guar gum. The tablets were fabricated by dry coating technique. In vitro evaluation of the prepared tablets was performed by the determination of the hardness, friability, content uniformity, and weight variation. The floating lag time and floating duration were also evaluated. Release profile of the prepared tablets was performed and analyzed. Furthermore, a stability study of the floating tablets was carried out at three different temperatures over 12 weeks. Finally, in vivo bioavailability study was done on human volunteers. All tablet formulas achieved < 0.5 min of floating lag time, more than 12 h of floating duration, and extended t (1/2). The drug release in all formulas followed zero-order kinetics. T4 and T8 tablets contained the least polymer concentration and complied with the dissolution requirements for controlled-release dosage forms. These two formulas were selected for further stability studies. T8 exhibited longer expiration date and was chosen for in vivo studies. T8 floating tablets showed an improvement in the drug bioavailability compared to immediate-release tablets (Vastrel® 20 mg).