Methamphetamine-related peptic ulcer perforation: a growing medical concern.

BACKGROUND: Many studies have been done in the literature on perforations due to substance abuse, and there are limited publications on perforations related to inhaled methamphetamine. Recently, in our clinic, we observed an increase in the number of patients with perforated peptic ulcer, which we think is secondary to a significant increase in the consumption of this drug. The main purpose of this study is to determine whether the use of inhaled methamphetamine known as 'fire and ice' is a factor directly related to peptic perforation and its complications and also to determine the demographic variables of patients with peptic ulcer perforation due to this substance use, in the context of the literature. METHODS: A retrospective study was conducted by examining the medical records of 29 gastric perforation patients who underwent surgical treatment in our clinic in 2021. Data were transferred to SPSS.23 (IBM Inc., Chicago, IL, USA) program and evaluated with statistical analysis. Normality assumptions of continuous variables were examined with Kolmogorov-Smirnov test, and variance homogeneity was examined with Levene's test. Bi-level comparisons, t-test if the data are normally distributed and Mann-Whitney U-test for bi-level comparisons where the data are not normally distributed were used. Relationships between categorical variables were examined by Chi-square test analysis. P<0.05 was accepted as the level of significance in all analyzes. RESULTS: Twenty-nine patients were divided into two groups as methamphetamine users (n=13) and non-users (n=16). There was a statistically significant difference according to the lower age in the group using methamphetamine (31.69-48.8-P=0.025). The pres-ence of PU history differed significantly between the groups (P=0.009). Interestingly, aspartate transaminase alanine aminotransferase values were lower in substance dependents (P=0.020). Furthermore, there was a significant difference in localization between groups (P<0.001). There was no statistically significant difference between the two groups in terms of gender, clinical presentation, and other laboratory values. CONCLUSION: Methamphetamine consumption, known as fire and ice, is an important risk factor for ulcer development and subsequent perforation, especially in young patients and long-term consumption of this narcotic substance. It has been determined that this risk factor, which is currently considered rare, has been seen in a very large number in a short time in our clinic. The use of this substance, which is considered a major social threat, is becoming more and more widespread, and this study is only a small part of the iceberg reflected in the general surgery clinic of a hospital.

Celecoxib Nanoformulations with Enhanced Solubility, Dissolution Rate, and Oral Bioavailability: Experimental Approaches over In Vitro/In Vivo Evaluation.

Celecoxib (CXB) is a Biopharmaceutical Classification System (BCS) Class II molecule with high permeability that is practically insoluble in water. Because of the poor water solubility, there is a wide range of absorption and limited bioavailability following oral administration. These unfavorable properties can be improved using dry co-milling technology, which is an industrial applicable technology. The purpose of this study was to develop and optimize CXB nanoformulations prepared by dry co-milling technology, with a quality by design approach to maintain enhanced solubility, dissolution rate, and oral bioavailability. The resulting co-milled CXB composition using povidone (PVP), mannitol (MAN) and sodium lauryl sulfate (SLS) showed the maximum solubility and dissolution rate in physiologically relevant media. Potential risk factors were determined with an Ishikawa diagram, important risk factors were selected with Plackett-Burman experimental design, and CXB compositions were optimized with Central Composite design (CCD) and Bayesian optimization (BO). Physical characterization, intrinsic dissolution rate, solubility, and stability experiments were used to evaluate the optimized co-milled CXB compositions. Dissolution and permeability studies were carried out for the resulting CXB nanoformulation. Oral pharmacokinetic studies of the CXB nanoformulation and reference product were performed in rats. The results of in vitro and in vivo studies show that the CXB nanoformulations have enhanced solubility (over 4.8-fold (8.6 ± 1.06 µg/mL vs. 1.8 ± 0.33 µg/mL) in water when compared with celecoxib pure powder), and dissolution rate (at least 85% of celecoxib is dissolved in 20 min), and improved oral pharmacokinetic profile (the relative bioavailability was 145.2%, compared to that of Celebrex®, and faster tmax 3.80 ± 2.28 h vs. 6.00 ± 3.67 h, indicating a more rapid absorption rate).

Vancomycin Containing PDLLA and PLGA/ß-TCP Inhibit Biofilm Formation but Do Not Stimulate Osteogenic Transformation of Human Mesenchymal Stem Cells.

Aims: Chronic osteomyelitis, including implant-related prosthetic joint infection, is extremely difficult to cure. We develop vancomycin containing release systems from poly(d,l-lactide) (PDLLA) and poly(d,l-lactide-co-glycolide) (PLGA) composites with beta-tricalcium phosphate (ß-TCP) to treat methicillin-resistant Staphylococcus aureus osteomyelitis. We ask whether vancomycin containing PDLLA/ß-TCP and PLGA/ß-TCP composites will prevent early biofilm formation, allow cell proliferation and osteogenic differentiation, and stimulate osteogenic signaling molecules in the absence of an osteogenic medium. Methods: Composites were produced and characterized with scanning electron microscopy. In vitro vancomycin release was assessed for 6 weeks. Biofilm prevention was calculated by crystal violet staining. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and osteosarcoma cell (SaOS-2) proliferation and differentiation were assessed with water soluble tetrazolium salt and alkaline phosphatase (ALP) staining. Real-time quantitative polymerase chain reaction defined osteogenic signaling molecules for hBM-MSCs. Results: Totally, 3.1 ± 0.2 mg and 3.4 ± 0.4 mg vancomycin released from PDLLA/ß-TCP and the PLGA/ß-TCP composites, respectively, and inhibited early biofilm formation. hBM-MSCs and SaOS-2 cells proliferated on the composites and stimulated ALP activity of cells. Runt-related transcription factor 2 (RUNX2) and SRY-Box transcription Factor 9 (SOX9) expressions were, however, lower with composites when compared with control. Conclusion: Vancomycin containing PDLLA/ß-TCP and PLGA/ß-TCP composites inhibited early biofilm formation and proliferated and differentiated hBM-MSCs and SaOS-2 cells, but osteogenesis-related RUNX2 and SOX9 transcription factors were not strongly expressed in the absence of an osteogenic medium for 14 days.

Do Thickening Agents Used in Dysphagia Diet Affect Drug Bioavailability?

Swallowing oral solid dosage forms is challenging in patients with dysphagia who are at risk of aspiration or choking. The most common method to facilitate drug administration in dysphagia patients is to mix the powdered drug with a small amount of thickened water, however little is known about the effects of this method on in vivo bioavailability of drugs. This study aimed to evaluate the impact of thickened liquids on dissolution rate and bioavailability of levetiracetam as a model drug. Powdered commercial tablets of levetiracetam, carbamazepine, atenolol and cefixime were mixed with water thickened with two commercial thickeners, modified maize starch (MS) and xanthan gam (XG), at three thickness levels: nectar, honey and pudding in test groups, and mixed with only water in the control group. At the first stage, the effects of thickened water on in vitro drug release of 4 drugs (levetiracetam, carbamazepine, atenolol and cefixime) were tested by using dialysis membrane method. Addition of both thickeners significantly reduced the release of three drugs compared to the control group, except carbamazepine. Levetiracetam which had the highest solubility was chosen as the model drug for in vivo experiments. In the second stage, New Zealand albino female rabbits (n=24) were divided into two groups as: control group (water+drug, n=6) and test group (thickened water+drug, n=18). Powdered levetiracetam tablets were mixed with water thickened with XG (n=9, 1.2%, 2.4%, 3.6%) and MS (n=9, 4%, 6%, 8%) at three thickness levels and administered to the rabbits by intragastric gavage. Blood samples were collected at 9 time points following administration. After two-weeks of wash-out, test groups were crossed over and sample collection was repeated. Blood samples were analysed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). An in vitro-in vivo correlation (IVIVC) model was developed using in vitro drug dissolution (%) and in vivo plasma concentrations of levetiracetam for control group and test groups. The peak plasma concentration (Cmax) was lower and time to reach Cmax (tmax) was relatively higher in test groups compared to control group. The lowest Cmax was detected at the highest thickness level, however, the differences between groups were not statistically significant (p=0.117 and p=0.495 for Cmax and tmax, respectively). No significant difference in total amount of levetiracetam absorbed (AUC) was found between groups (p=0.215 and p=0.183 for AUCinfinity and AUClast, respectively). The comparisons according to the type of thickener also revealed that pharmacokinetic parameters did not significantly differ between groups, except for a significantly lower Cmax when drug was mixed with MS-thickened water at nectar consistency (1.2%) compared to drug mixed with XG (4%) at the same thickness level (p=0.038). A good correlation was observed between in vitro and in vivo data, which was characterized by higher r2 values as the concentration of the thickening agents was increased, but not for all thickness levels studied, indicating an inability of this in vitro model to fully predict the in vivo response. These results suggest that regardless of the thickness level, the administration of levetiracetam with two commercial thickening agents commonly used in dysphagia for safe swallowing, do not affect the pharmacokinetic efficiency and thus, the bioavailability of the drug.

A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies.

Antiviral drugs have gained much more attention in recent years due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and many drug candidates are currently under investigation in order to end pandemic. Molnupiravir, a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, is one of the promising candidates for SARS-CoV-2 treatment. In this study, a RP-HPLC method was developed for the determination of Molnupiravir and applied for in vitro permeability studies of self-emulsifying drug delivery system (SEDDS) formulations using Caco-2 cell line. Discovery® HS C18 Column (75 ×4.6 mm, 3 µm) was used at 30 °C. Isocratic elution was performed with ACN:water (20:80 v/v) mixture. The flow rate was 0.5 mL/min and UV detection was at 240 nm. Molnupiravir eluted within 5 min. Molnupiravir was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions. Peak homogeneity data of Molnupiravir in the stressed samples peak obtained using photodiode array detector, in the stressed sample chromatograms, demonstrated the specificity of the method for their estimation in presence of degradants. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines and found to be linear within the range 0.1-60.0 µg/mL. The method was simple, rapid, selective, sensitive, accurate, precise, robust and rugged. Thus, it was applied successfully for permeability quantitation of Molnupiravir in nanoformulations. The apparent permeability of Molnupiravir in SEDDS formulations, which have droplet size under 350 nm, was calculated as 3.20 ± 0.44 × 10-6 cm/s.

Current approaches and future prospects of nanofibers: a special focus on antimicrobial drug delivery.

Antibacterial nanofibers have a great potential for effective treatment of infections. They act as drug reservoir systems that release higher quantities of antibacterial agents/drug in a controlled manner at infection sites and prevent drug resistance, while concomitantly decreasing the systemic toxicity. With this drug delivery system, it is also possible to achieve multiple drug entrapment and also simultaneous or sequential release kinetics at the site of action. Therefore, advances in antibacterial nanofibers as drug delivery systems were overviewed within this article. Recently published data on antibacterial drug delivery was also summarised to provide a view of the current state of art in this field. Although antibacterial use seems to be limited and one can ask that 'what is left to be discovered?'; recent update literatures in this field highlighted the use of nanofibers from very different perspectives. We believe that readers will be benefiting this review for enlightening of novel ideas.

Current status of micro/nanomotors in drug delivery.

Synthetic micro/nanomotors (MNMs) are novel, self-propelled nano or microscale devices that are widely used in drug transport, cell stimulation and isolation, bio-imaging, diagnostic and monitoring, sensing, photocatalysis and environmental remediation. Various preparation methods and propulsion mechanisms make MNMs "tailormade" nanosystems for the intended purpose or use. As the one of the newest members of nano carriers, MNMs open a new perspective especially for rapid drug transport and gene delivery. Although there exists limited number of in-vivo studies for drug delivery purposes, existence of in-vitro supportive data strongly encourages researchers to move on in this field and benefit from the manoeuvre capability of these novel systems. In this article, we reviewed the preparation and propulsion mechanisms of nanomotors in various fields with special attention to drug delivery systems.

Neuroprotective Efficiency of Cyclosporine After Traumatic Brain Injury in Rats.

AIM: To evaluate the possible neuroprotective effects of systemic administration of cyclosporine (Cyclosporin A) after traumatic brain injury in rats. MATERIAL AND METHODS: The modified Feeney method was used as the trauma model in male Sprague Dawley rats. After the trauma, 20 mg/kg of cyclosporine was administered to the one group of the rats (n=12) intraperitoneally. Twenty-four hours after injury, the subjects were sacrificed, and brain samples were removed. The level of brain edema was evaluated through the wet-dry weight method, the lipid peroxidation ratio, and histological examination by transmission electron microscopy. RESULTS: The level of brain edema and lipid peroxidation ratio significantly decreased in the rats that received cyclosporine. Ultrastructural neurodestruction was graded, and a comparison of the scores between the experimental groups revealed significant neuroprotective effects of cyclosporine. CONCLUSION: The results demonstrated that systemic administration of cyclosporine produces a statistically significant decrease in both the level of brain edema and lipid peroxidation ratio when compared with "no treatment". Cyclosporine, which is regularly used as an immunosuppressant agent, is also known to prevent opening of the mitochondrial permeability transition pore by unbinding mitochondrial matrix cyclophilin. Regulation of transition pore for mitochondrial permeability by cyclosporine implies that mitochondrial dysfunction following traumatic brain injury is an important event in the progressive loss of neuronal tissue.

Composite nanofibers incorporating alpha lipoic acid and atorvastatin provide neuroprotection after peripheral nerve injury in rats.

Despite the new treatment strategies within the last 30 years, peripheral nerve injury (PNI) is still a worldwide clinical problem. The incidence rate of PNIs is 1 in 1000 individuals per year. In this study, we designed a composite nanoplatform for dual therapy in peripheral nerve injury and investigated the in-vivo efficacy in rat sciatic nerve crush injury model. Alpha-lipoic acid (ALA) was loaded into poly lactic-co-glycolic acid (PLGA) electrospun nanofibers which would release the drug in a faster manner and atorvastatin (ATR) loaded chitosan (CH) nanoparticles were embedded into PLGA nanofibers to provide sustained release. Sciatic nerve crush was generated via Yasargil aneurism clip with a holding force of 50 g/cm2. Nanofiber formulations were administered to the injured nerve immediately after trauma. Functional recovery of operated rat hind limb was evaluated using the sciatic functional index (SFI), extensor postural thrust (EPT), withdrawal reflex latency (WRL) and Basso, Beattie, and Bresnahan (BBB) test up to one month in the post-operative period at different time intervals. In addition to functional recovery assessments, ultrastructural and biochemical analyses were carried out on regenerated nerve fibers. L-929 mouse fibroblast cell line and B35 neuroblastoma cell line were used to investigate the cytotoxicity of nanofibers before in-vivo experiments. The neuroprotection potential of these novel nanocomposite fiber formulations has been demonstrated after local implantation of composite nanofiber sheets incorporating ALA and ATR, which contributed to the recovery of the motor and sensory function and nerve regeneration in a rat sciatic nerve crush injury model.

A Snapshot on the Current Status of Alzheimer's Disease, Treatment Perspectives, in-Vitro and in-Vivo Research Studies and Future Opportunities.

Alzheimer's Disease (AD) is one of the most challenging diseases faced by humankind. AD is still not classified as curable because of the complex structure of pathologies underlying it. As the mean life expectancy of the world population constantly increases, the prevalence of AD and treatment costs for AD also grow rapidly. Current state of the art for AD treatment mainly consists of palliative therapy aimed at providing symptomatic relief and improving the standard of living in patients with AD. However, different research groups are working on more effective and safe drug delivery options aimed at both symptomatic relief and treatment of the underlying mechanisms. In this review, the current prevalence of AD, health costs, pathologies, and available treatment options including the ones in the market and/or under trial have been reviewed. Data in the existing literature have been presented, and future opportunities have been discussed. It is our belief that these nanotechnological products provide the required efficacy and safety profiles to enable these formulations go through phase studies and enter the market after regulatory authority approval, as with cancer. Last, but not the least the metabolomic studies will be providing useful informative data on the early diagnosis of AD, thus may be clinical implications might be delayed with the administration of therapeutic agents at the initial state of the disease.

Evaluation of improved oral bioavailability of ritonavir nanosuspension.

The main objective of this study was to evaluate the pharmacokinetics of ritonavir (RTV) nanosuspension in rats in both fed and fasted state in comparison with coarse powder, physical mixture and commercial product (Norvir®). The point to point relation model was generated between the results of in vitro dissolution and in vivo pharmacokinetic studies. The oral RTV nanosuspension was prepared with microfluidization method. Nanosuspension was obtained with 540-550 nm of particle size, 0.1-0.4 of particle size distribution and about -20 mV of zeta potential values. According to in vivo pharmacokinetic studies in rats, Cmax and AUC0-t values in nanosuspension displayed an 8.9- and 12.5-fold increase compared to the coarse powder, and a 1.9- and 2.1-fold increase compared to the commercial product, respectively in the fed group. The point to point relation model showed that the correlation model was significant. It is concluded that nanosuspension is a promising drug delivery system to enhance oral bioavailability of ritonavir.

Current Advances in Nanopharmaceuticals.

Nanotechnology is one of the hot topics not only in pharmaceutical industry, but also in many others that are currently existing in our daily lives. Since the last two decades, many nanotechnology based drugs have been introduced in the market providing new and optimized treatment perspectives. In addition to that, local regulatory authorities also meet new challenging issues regarding the development process of the nanopharmaceuticals. It is a clear fact that the novelty of nanopharmaceuticals also include a more precise clarification process on the efficacy and safety of the formulations for the benefit of public health. Therefore, current scientific improvements as well as current regulatory perspectives are reflected in this review.

Novel advances in targeted drug delivery.

Developing a new drug molecule is not only time-consuming and expensive, but also mostly a failing process. However, improving bioavailability, targetability, efficacy or safety of old drugs could be more effective way to use them in clinic. For these purposes, so many strategies including individualising drug therapy, nanoparticle-based drug delivery systems, drug conjugates, therapeutic drug monitoring, stimuli-sensitive targeted therapy are investigated intensely. Depending on the desired application or targeted site, nanoparticles can be administrated as orally, locally, topically and systemically. Currently, the Food and Drug Administration and the European Medicines Agency approved nanoparticles are mostly aimed to treat cancer. Although some of these formulations were approved by Food and Drug Administration and/or European Medicines Agency to use in clinic, most of them have fell down to pass either pre-clinical or clinical trials. To have high approval rate, failure reasons need to be better understand.

Therapeutic efficacy of folate receptor-targeted amphiphilic cyclodextrin nanoparticles as a novel vehicle for paclitaxel delivery in breast cancer.

PURPOSE: The aim of this study is to test folate-conjugated cyclodextrin nanoparticles (FCD-1 and FCD-2) as a vehicle for reducing toxicity and increasing the antitumor efficacy of paclitaxel especially for metastatic breast cancer. METHODS: For the evaluation of PCX-loaded FCD nanoparticles, animal studies were realised in terms of survival rate, tumour size, weight change, metastazis and histopathological examination. RESULTS: FCD-1 displayed significant advantages such as efficient targeting of folate receptor positive breast cancer cells and having considerably lower toxicity compared to that of Cremophor®. When loaded with paclitaxel, FCD-1 nanoparticles, which have smaller particle size, neutral zeta potential, high encapsulation efficiency and better loading capacity for controlled release, emerged as an effective formulation in terms of cytotoxicity and high cellular uptake. In an experimental breast cancer model, anticancer activity of these nanoparticles were compatible with that of paclitaxel in Cremophor® however repeated administrations of FCD-1 nanoparticles were better tolerated by the animals. These nanoparticles were able to localise in tumour site. Both paclitaxel-loaded FCD-1 and FCD-2 significantly reduced tumour burden while FCD-1 significantly improved the survival. CONCLUSIONS: Folate-conjugated amphiphilic cyclodextrin nanoparticles can be considered as promising Cremophor®-free, low-toxicity and efficient active drug delivery systems for paclitaxel.

Cost Evaluation of Inhaler Therapies Used in Respiratory Diseases: 1998--2015 Period in Turkey.

BACKGROUND: With the rise in life expectancy, the burden of chronic diseases, including obstructive pulmonary diseases, has increased throughout the world. OBJECTIVES: To evaluate the sales trends of inhaler pharmaceuticals. METHODS: The changes in box sales and sales amounts (in Turkish lira) of inhaler pharmaceuticals during the period 1998 to 2015 were examined and sales were projected for the next 3 years. Pharmaceuticals were classified according to form and pharmacological groups. RESULTS: The sales of inhaler pharmaceuticals have increased rapidly since 2008. The fastest increase in consumption has occurred in short-acting ß2 agonist preparations and nebulizer pharmaceuticals. Inhaled corticosteroid and long-acting ß2 agonist combination sales have been the highest since 2002, when these products entered the Turkish market. CONCLUSIONS: The inhaler pharmaceutical market has grown over the years, and this growth will continue in the future. The increased use of short-acting preparations, which should be used as symptom relievers, indicates that treatment management continues to be inadequate.

Localized delivery of methylprednisolone sodium succinate with polymeric nanoparticles in experimental injured spinal cord model.

With important social and economic consequences, spinal cord injuries (SCIs) still exist among major health problems. Although many therapeutic agents and methods investigated for the treatment of acute SCI, only high dose methylprednisolone (MP) is being used currently in practice. Due to the serious side effects, high dose systemic MP administration after SCI is a critical issue that is mostly considered controversial. In our study, it is aimed to develop a nanoparticle-gel combined drug delivery system for localization of MP on trauma site and eliminating dose-dependent side effects by lowering the administered dose. For this purpose, methyl prednisolone sodium succinate (MPSS) loaded polycaprolactone based nanoparticles were developed and embedded in an implantable fibrin gel. The effects of MPSS delivery system are evaluated on an acute SCI rat model, by quantification the levels of three inflammatory cytokines (interleukin-1ß, interleukin-6 and caspase-3) and assessment of the damage on ultrastructural level by transmission electron microscopy. Developed NP-gel system showed very similar results with systemic high dose of MPSS. It is believed that developed system may be used as a tool for the safe and effective localized delivery of several other therapeutic molecules on injured spinal cord cases.

Nanofibers: New Insights for Drug Delivery and Tissue Engineering.

Nanofibers became one of the major research areas for drug delivery and tissue engineering applications in the last decade. Depending on the simplicity of the preparation method and high drug loading capacity, nanofibers provide many advantages for therapeutic perspectives. In addition, combined systems such as embedding nanoparticles into the nanofiber structures provide a second option for delivery of dual active ingredients in the same formulation. The release rate of the active ingredients can also be modified easily by the formulation parameters depending on the desired release time for treatment. Nanofibers systems are used for the delivery of antibiotics, anticancer drugs, analgesics, hemostatic agents and various proteins for tissue engineering purposes. In addition, various applications such as medical device coating also provide new insights for the clinical use of nanofibers. The most commonly used technique for preparation of nanofibers is the electrospinning, which provides feasibility background for scale up process from laboratory to the industrial applications. The main boundary for nanofibers is the limitations for systemic route. Nanofibers are mainly designed for the delivery of active ingredients for local purposes. Regardless of the therapeutic aim, nanofibers are also perfect 3 dimensional structures that are suitable for tissue regeneration. They provide matrix structure for cell regeneration especially in applications for wound healing. This review is mainly focused on the recent advances on the preparation of nanofibers, applications for drug delivery, tissue engineering and wound healing purposes.

Antitumor Efficacy of Bacillus Calmette-Guerin Loaded Cationic Nanoparticles for Intravesical Immunotherapy of Bladder Tumor Induced Rat Model.

For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapy after surgical transurethral resection. Bacillus Calmette-Guerin (BCG) is a live attenuated Mycobacterium of the same family as tuberculosis, that is capable of inducing a local inflammatory response upon instillation into the bladder. Intravesical therapy with BCG has proved to be more effective in the prophylaxis and treatment of superficial bladder tumors than most chemotherapeutic agents used for the same indication. However, compared to intravesical chemotherapy, BCG immunotherapy provokes more pronounced local and systemic reactions. In addition to the commonly induced granulomatous inflammatory changes in the bladder, which produce irritative symptoms, this therapy may cause systemic side effects varying from mild malaise and fever to, in rare instances, life-threatening or fatal sepsis. Nanoparticles with positive surface charge and mucoadhesive properties were developed to overcome these side effects. Hence, the aim of this study was to optimize and evaluate cationic chitosan (CS) nanoparticles encapsulating BCG in terms of antitumor efficacy after intravesical administration in bladder tumor, induced in rat model. It was found that nanoparticle formulations of 269-375 nm in size can be produced with 42% encapsulation efficiency. The zeta potential was positive and was suitable for intravesical administration. Antitumor efficacy was determined over the parameters of histopathological evaluation, survival rate and mean bladder weight in comparison to treatment with commercial BCG solution. Concerning survival rates, BCG-loaded chitosan nanoparticles resulted in significantly longer survival than BCG commercial product (up to 86 days of survival with no systemic side effects). When compared to healthy bladder weight averages, all groups (especially BCG commercial solution) showed higher bladder weights confirming tumor formation. Histopathological findings confirmed antitumor activity in all treatment groups and optimum findings were observed in groups treated with CS nanoparticles encapsulating BCG. At the same time, significant nanoparticle accumulation in bladder tissues was observed especially for BCG-loaded CS group. In this study, it was clearly observed that cationic CS nanoparticles provide a significantly improved perspective in intravesical immunotherapy of bladder tumors.

Effects of tadalafil-Type-V phosphodiesterase enzyme inhibitor-On rats with spinal trauma.

In this research, the effect of tadalafil, a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, on rats with spinal trauma was evaluated. The evaluation consisted of neurological examination and biochemical parameters. Twenty healthy male Wistar albino rats were used in this study. They were separated into three groups: tadalafil-receiving (TD) group (n=7), laminectomy and trauma (LT) group (n=7), and just laminectomy group (n=6). The TD group received daily dose of tadalafil (10 mg/kg) for a week along with bait and water. Each rat's spinal cord was dissected with utter caution. The spinal cord was traumatized by Allen's weight-drop method. Using a standard apparatus, 5 g of weight was dropped from a height of 10 cm on the spinal cords of the TD and LT (laminectomy+trauma) group. No extra maneuvers were conducted on the laminectomy group. A day later, the rat's functional neurological status was examined followed by re-exploration of the spinal cord for sampling 1 cm of tissue. The Tarlov scale was used to evaluate the functional neurological status. The modified Tarlov scale was rated to be significantly higher in the TD group than that in the LT group. For the biochemical parameters, malondialdehyde (MDA) and cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) involved in the inflammatory process were examined. MDA--an indicator of lipid peroxidation--was found to be significantly lower in the TD group compared with that in the LT group. TNF-α and IL-6 levels were also found to be lower in the TD group compared with those in the LT group. Shortly, this research showed that the use of TD group in spinal trauma resulted in better neurological outcome and significant improvement in biochemical parameters.