OBJECTIVE:Sleep deprivation poses critical safety risks in high-stakes professions, where traditional stimulants often fail to sustain cognitive performance. Addressing the need for novel cognitive enhancers, this study compared the effects of modafinil and caffeine with novel nicotinic (AVL-3288) and glutamatergic (CX516) positive allosteric modulators on behavior and memory in severely sleep-deprived mice. METHODS:Male C57BL/6 mice underwent 48 hours of paradoxical sleep deprivation before receiving intraperitoneal doses of modafinil (300 mg/kg), caffeine (10 mg/kg), AVL-3288 (1, 2 mg/kg), CX516 (40, 80 mg/kg), or vehicle. A behavioral test series assessed locomotor activity (Open Field), anxiety (Elevated Plus Maze), reward-based working and spatial memory (Eight-Arm Radial Maze), escape-based spatial memory (Barnes Maze), and depressive mood (Tail Suspension). RESULTS:Modafinil markedly increased locomotor activity and suppressed appetite. Caffeine, AVL-3288 (1 mg/kg), and CX516 (40 mg/kg) improved reward-based working memory (Eight- Arm Radial Maze). However, these same agents impaired performance in the escape-based spatial reference memory task (Barnes Maze). No mood-altering effects were observed. The novel modulators displayed complex, non-dose-dependent profiles. DISCUSSION:Under severe sleep deprivation, specific wakefulness-enhancing substances can yield contrasting outcomes, enhancing reward-associated memory while negatively affecting escape-associated memory. These divergent outcomes suggest that neuromodulation during severe sleep deprivation exerts task-dependent behavioral effects, though the precise mechanisms driving the differences between the two maze paradigms remain to be elucidated. CONCLUSION:Pharmacological interventions under severe sleep deprivation can produce complex, bidirectional effects on cognition. This highlights that cognitive enhancement is likely task-dependent rather than global, necessitating a comprehensive assessment of diverse behavioral domains.

Objective: We aimed to develop "interactive pharmacokinetics (PK)", an open-source, Python-based software package with a user-friendly graphical user interface. Our main goal was to overcome the cost and complexity barriers to industry-standard PK modeling tools and to facilitate the practical application of theoretical PK principles for students and researchers. Methods: The software employs one, two, and three-compartment models, solving systems of differential equations to simulate drug concentration-time profiles. Parameter estimation is performed using non-linear optimization algorithms to minimize the sum of squared logarithmic errors. The platform is developed in Python, using NumPy and SciPy for core computations and the multiprocessing library for parallel processing of population data. Results: A fully integrated, functional software application with a userfriendly graphical user interface was created. The platform enables users to run simulations and visualize results, including key parameters such as C and T . It performs de novo parameter estimation from max max patient data for one-compartment models and generates novel two-and three-compartment models using a priori data. Conclusion: The software provides an accessible, no-cost tool for fundamental PK simulation and modeling. It serves as both a valuable pedagogical instrument for pharmacology education and a capable platform for preliminary research, particularly in resource-limited environments. Future work should focus on comprehensive validation against established software.

Objective: The process of conducting medical research on human subjects is secured by a number of regulations from its planning phase through its publication as an original article. Ethics Committees (ECs) play an important role in the follow-up and evaluation of the study. In this study, we present an evaluation of the experiences of the “Clinical Research Ethics Committee” of a university. Methods: The characteristics of EC applications, reasons for rejection (technical, scientific, ethical), and files that did not reapply to the committee after the revision request were analyzed. Results: One thousand and fifty-seven (73.96%) of the 1429 files were accepted with minor corrections at the first examination and 15 files were rejected (1.04%). Of the applications, 357 (24.98%) were returned to the EC agenda with major correction requests. Scientific reasons were reported in 19 (90.5%) of the rejected files, ethical reasons were reported in 12 (57%) and technical reasons were reported in 8 (38.1). The rejection rate increased to 8.24% when the same files were reevaluated and did not reapply to the EC after the revision request (6.8%). Conclusion: ECs seek revisions for a significant portion of submissions and offer researchers scientific and ethical advice. The majority of the applications were approved by this consultation. In our study, most of the files that did not receive approval from the EC were actually those that did not return after the revision request. The difficulties associated with the legislation appear to be an important reason for researchers to withdraw their application files.

PURPOSE:This study evaluated the performance of three generative AI models-ChatGPT- 4o, Gemini 1.5 Advanced Pro, and Claude 3.5 Sonnet-in producing case-based rational pharmacology questions compared to expert educators. METHODS:Using one-shot prompting, 60 questions (20 per model) addressing essential hypertension and type 2 diabetes subjects were generated. A multidisciplinary panel categorized questions by usability (no revisions needed, minor or major revisions required, or unusable). Subsequently, 24 AI-generated and 8 expert-created questions were asked to 103 medical students in a real-world exam setting. Performance metrics, including correct response rate, discrimination index, and identification of nonfunctional distractors, were analyzed. RESULTS:No statistically significant differences were found between AI-generated and expert-created questions, with mean correct response rates surpassing 50% and discrimination indices consistently equal to or above 0.20. Claude produced the highest proportion of error-free items (12/20), whereas ChatGPT exhibited the fewest unusable items (5/20). Expert revisions required approximately one minute per AI-generated question, representing a substantial efficiency gain over manual question preperation. Nonetheless, 19 out of 60 AI-generated questions were deemed unusable, highlighting the necessity of expert oversight. CONCLUSION:Large language models can profoundly accelerate the development of high-quality assessment questions in medical education. However, expert review remains critical to address lapses in reliability and validity. A hybrid model, integrating AI-driven efficiencies with rigorous expert validation, may offer an optimal approach for enhancing educational outcomes.

Acute poisoning is a major cause of pediatric emergency department (PED) visits, with the COVID-19 pandemic potentially altering exposure risks and care-seeking behaviors. This study compares pediatric poisoning characteristics before and during the pandemic. A retrospective analysis was conducted at the Gazi University PED between January 2018 and June 2022. Patients aged 1 month-18 years diagnosed with poisoning were identified via ICD codes grouped into before pandemic and during pandemic cases. A systematic random sampling yielded 178 BP (before the pandemic) and 94 DP (during the pandemic) cases with complete data. Demographic and clinical properties of cases were analyzed. The mean age was significantly higher during the pandemic (BP:7.63±0.49; DP:9.27±0.69). A higher prevalence of chronic diseases was noted in DP cases (BP:0.29±0.049; DP:0.57±0.100). Hotline consultations were higher in DP period (54.5% vs.72.5%) while hospitalization rates were lower (55% vs. 35.2%). While suicide attempts were significantly higher in women compared to men before the pandemic, this difference disappeared during the pandemic period (BP:8.6% of males vs. 37.2% of females; DP: 25% of males vs. 39% of females). The COVID-19 pandemic significantly impacted pediatric poisoning profiles, underscoring the need for targeted prevention strategies and adaptive emergency protocols.

AIM This study aimed to develop a blended training module focusing on ethical approaches within general surgery residency training and to assess the impact of this training on participants. METHODS Based on the literature review and input from both general surgery residents and trainers, 14 topics were identified, and corresponding learning objectives were formulated. The training was conducted through a blended learning module, which encompassed online video presentations alongside face-to-face sessions involving real-life cases. Assessment of the training involved administering test-formatted exams both before and after the training, which assessed the learning objectives of the 14 topics. These exams comprised multiple-choice questions and true/false inquiries based on case-based propositions. Additionally, feedback regarding the training was solicited from the residents. RESULTS The study involved 20 general surgery residents. Assessment revealed a statistically significant increase in exam success among the residents after the training (p<0.001). Additionally, feedback indicated that the training model was effective. CONCLUSIONS Developing a blended learning module that combines online and face-to-face education, supplemented with real-life case studies, and incorporating discussions on ethical dilemmas during face-to-face sessions, along with assessment through exams, will significantly enhance the proficiency of residents in surgical ethics.

PURPOSE:Artificial intelligence, specifically large language models such as ChatGPT, offers valuable potential benefits in question (item) writing. This study aimed to determine the feasibility of generating case-based multiple-choice questions using ChatGPT in terms of item difficulty and discrimination levels.METHODS:This study involved 99 fourth-year medical students who participated in a rational pharmacotherapy clerkship carried out based-on the WHO 6-Step Model. In response to a prompt that we provided, ChatGPT generated ten case-based multiple-choice questions on hypertension. Following an expert panel, two of these multiple-choice questions were incorporated into a medical school exam without making any changes in the questions. Based on the administration of the test, we evaluated their psychometric properties, including item difficulty, item discrimination (point-biserial correlation), and functionality of the options.RESULTS:Both questions exhibited acceptable levels of point-biserial correlation, which is higher than the threshold of 0.30 (0.41 and 0.39). However, one question had three non-functional options (options chosen by fewer than 5% of the exam participants) while the other question had none.CONCLUSIONS:The findings showed that the questions can effectively differentiate between students who perform at high and low levels, which also point out the potential of ChatGPT as an artificial intelligence tool in test development. Future studies may use the prompt to generate items in order for enhancing the external validity of the results by gathering data from diverse institutions and settings.

OBJECTIVE:Caffeine and modafinil are used to reverse effects of sleep deprivation. Nicotinic alpha-7 receptor and AMPA receptor positive allosteric modulators (PAM) are also potential substances in this context. Our objective is to evaluate the effects of caffeine, modafinil, AVL-3288 (nicotinic alpha-7 PAM) and CX516 (AMPA receptor PAM) on cognition and mood in a model of sleep deprivation. METHOD:Modified multiple platform model is used to sleep-deprive mice for 24 days, for 8 h/day. Vehicle, Modafinil (40 mg/kg), Caffeine (5 mg/kg), CX516 (10 mg/kg), and AVL3288 (1 mg/kg) were administered intraperitoneally daily. A cognitive test battery was applied every six days for four times. The battery that included elevated plus maze, novel object recognition, and sucrose preference tests was administered on consecutive days. RESULTS:Sleep deprivation decreased novel object recognition skill, but no significant difference was found in anxiety and depressive mood. Caffeine administration decreased anxiety-like behavior in short term, but this effect disappeared in chronic administration. Caffeine administration increased memory performance in chronic period. AVL group showed better memory performance in short term, but this effect disappeared in the rest of experiment. Although, in the modafinil group, no significant change in mood and memory was observed, anhedonia was observed in the chronic period in vehicle, caffeine and modafinil groups, but not in AVL-3288 and CX-516 groups. CONCLUSION:Caffeine has anxiolytic effect in acute administration. The improvement of memory in chronic period may be associated with the neuroprotective effects of caffeine. AVL-3288 had a short-term positive effect on memory, but tolerance to these effects developed over time. Furthermore, no anhedonia was observed in AVL-3288 and CX516 groups in contrast to vehicle, caffeine and modafinil groups. This indicates that AVL-3288 and CX516 may show protective effect against depression.

Introduction: Screening Tool of Older Person's Prescriptions (STOPP) / Screening Tool to Alert Doctors to the Right Treatment (START) is among the most forthcoming lists developed to detect potentially inappropriate prescribing, which consists of potentially inappropriate medications and potential prescription omissions. Turkish Inappropriate Medication Use in the Elderly (TIME) was developed based on STOPP/START version 2 for the eastern European population. We aimed to compare the effectiveness of STOPP/ START and TIME in detecting potentially inappropriate prescribing, potentially inappropriate medications, and potential prescribing omissions. Materials and methods: Eighty-five patients who presented to Gazi University Hospital's Geriatrics Outpatient Clinic between November 2020 and March 2022 were included in this study. The patients' detailed clinical records were evaluated according to TIME and STOPP/START. The numbers of potentially inappropriate prescribing, potentially inappropriate medications, and potential prescribing omissions were determined. Results: Median number of potentially inappropriate prescribing detected according to TIME was significantly higher than according to STOPP/START (6 [IQR4-7] vs. 3 [IQR 2-5], p<0.001). However, no significant difference was observed in the number of potentially inappropriate medications detected. The number of patients meeting potentially inappropriate prescribing criteria according to the TIME was significantly higher than START, which was attributable primarily to the disparity in the vaccination category. Conclusion: Our results suggest that TIME is more successful in detecting potentially inappropriate prescribing than STOPP/START in Turkish geriatric patients. This success was probably due to the better performance of TIME in detecting potential prescribing omissions. Further studies are needed to confirm these findings.

Introduction: The prevalence of polypharmacy in older people contributes to potentially inappropriate prescribing, which is evaluated using various criteria. Depressive disorders are serious issues for older adults. In this study, the prescribing rates of potentially inappropriate antidepressants in older age groups in T & uuml;rkiye were compared with younger age groups. Materials and Method: All electronic prescriptions including those for antidepressants, in T & uuml;rkiye, issued by family physicians in 2019 were obtained using the Prescription Information System. Data were analyzed using the Beers Criteria 2019 update. Results: Of all prescriptions, 0.63% written for older people (65 years and over) were "Potentially Inappropriate Medication" classified antidepressant medications. A significantly lower percentage of "Potentially Inappropriate Medication" classified prescriptions, was observed for older people compared to the rate of total prescriptions (30.6% vs 32%). Paroxetine and amitriptyline had the highest prescription rates for older people. Older people received significantly more "Drugs to be Used With Caution" (35.6% vs. 32%). The top five most frequently prescribed "Drugs to be Used With Caution" for older people were escitalopram, sertraline, duloxetine, citalopram, and mirtazapine. Conclusions: There was a lower rate of prescribing of "Potentially Inappropriate Medication" for older people (65 years and over) than for younger (between 18-65 years) people. This suggests that family physicians are aware of the potential inappropriateness of specific antidepressants and prescribe them less frequently. Additionally, increased prescribing of "Drugs to be Used With Caution" in elderly can be associated with the limited availability of completely safe drugs in this population.

Background: Elderly comprises a specific group due to possible alterations in the effects of drugs and comorbidities. We aimed to identify for the first time the characteristics and rates regarding the inappropriate prescriptions of cardiovascular system medications in the geriatric age group in Turkey. Methods: Cardiovascular system medications prescribed electronically by family physicians to patients aged 65 and over, in the years 2015 and 2016, were obtained through Prescription Information System administered by the Ministry of Health. Evaluation of potentially inappropriate prescriptions was done according to the "Beers Criteria 2015 update." Prescription rates for each group were evaluated under sub-breakdowns for the specialty of family physicians, gender, age groups, and "Nomenclature of Territorial Units for Statistics" regions. Results: Approximately 65 million prescriptions were evaluated. The rate of potentially inappropriate cardiovascular medication prescribing was 0.33%. This raised to 11.56% when "drugs to be used with caution" were included. It was observed that potentially inappropriate drugs have been prescribed more by specialist family physicians. The most frequently prescribed potentially inappropriate drugs were doxazosin in the diagnosis of hypertension and methyldopa regardless of indication. Diclofenac-warfarin was the most commonly prescribed concomitant drug use in the potentially clinically important drug-drug interactions group. The rate of potentially inappropriate drug prescribing was higher in males and in aged 80 years and older. Conclusions: This pharmacoepidemiological study draws attention to potentially inappropriate cardiovascular system drugs prescribed in primary care settings to the elderly. The rate of potentially inappropriate cardiovascular system drug prescribed was found to be very low in Turkey.

Aim: Admission to the emergency department (ED) due to a hypertensive attack (HTA) is common.Our study explores patients' compliance with HTA to blood pressure (BP) treatment, the interrelationship of BP values, and their interaction with other factors.Material and Method: Two hundred and sixty seven patients admitted to our ED with the complaint of HTA and previously diagnosed with hypertension were enrolled in this study.During the data collection phase of the study, the Hill-Bone Compliance to High Blood Pressure Therapy Scale (HBCS) and a questionnaire including the sociodemographic characteristics, hypertension-related status, and dietary habits were filled in through face-to-face interviews with the patients. Results:The patients' mean systolic blood pressure (SBP) was 168.77±26.83,and their mean diastolic blood pressure (DBP) was 98.03±10.44 at the time of admission.Their mean HBCS score turned out to be 4.78±1.79.The mean HBCS total scores tended to decrease significantly as the level of education increased.The patients restricting their salt intake and going on a diet achieved lower HBCS scores, and the difference between the groups was significant.When the patients' mean SBP and DBP were compared with their HBCS scores, a moderately low correlation was noted between the mean HBCS scores and the mean SBP. Conclusion:The patients with an educational status at the primary school level and below presented lower compliance with treatment.When the HBCS scores were compared in terms of whether the patients went on a diet or not, the mean scores of the dieters turned out to be lower.The patients with high compliance with treatment presented lower SBP and DBP.

Aim: Automatic item generation is "a process of using models to generate items using computer technology". The use of automatic item generation typically involves one of three primary methods: syntax-based, semantic-based, and template-based. Non-template automatic item generation approaches leverage natural language processing techniques. A study showed the potential of using template-based automatic item generation to create high-quality multiple-choice questions for assessing clinical reasoning in Turkish, marking a first in the field. However, the findings of the study were based only on expert opinions, necessitating further research to examine the psychometric qualities of Turkish items. The aim of this study was to reveal psychometric characteristics of the first Turkish case-based multiple-choice questions generated by using automatic item generation in medical education. Methods: This was a psychometric study. Three Turkish case-based multiple-choice questions generated using template-based automatic item generation on essential hypertension were included in an exam that 281 fourth-year medical students participate in. This examination was carried out in-person in classroom settings under proctor supervision. Item difficulty and item discrimination (point-biserial correlation) were calculated, and non-functioning distractors were determined. Results: All three items had acceptable levels (higher than 0.20) of point-biserial correlation (p<0.001). The item difficulty levels indicated the presence of one easy, one moderate, and one difficult question. Each item had 2-3 non-functioning options among five options. All three items had acceptable levels (higher than 0.20) of point-biserial correlation (p<0.001). The item difficulty levels indicated the presence of one easy, one moderate, and one difficult question. Each item had 2-3 non-functioning options among five options. Conclusions: The results indicated that the items successfully discriminate between high and low performers, providing validity evidence on the quality of the questions in evaluating students' comprehension of the subject. Additionally, the findings suggest that it is feasible to create multiple-choice questions with different difficulty levels in Turkish using a single automatic item generation model. This study demonstrated for the first time that automatic generation of case-based multiple-choice questions in Turkish produces acceptable psychometric characteristics in an authentic assessment setting in medical education. The ability to automatically generate effective multiple-choice questions in Turkish holds promise for enhancing the efficiency of written assessment in Turkish medical education.

The circadian rhythm is a critical system that governs an organism’s functions in alignment with the light-dark cycle. Melatonin release from the pineal gland plays a crucial role in regulating the internal clock of the body. Multiple neurotransmitter systems in the central nervous system are linked to the release of melatonin. In this review, the relationship between circadian rhythm, melatonin secretion and various neurotransmitter systems are mainly discussed. Serotonin regulates the circadian rhythm through projections from raphe nuclei. Agomelatine is an example of the synergistic interaction between melatonin and serotonin. Melatonergic agents and selective serotonin reuptake inhibitors also exert notable impacts on depression in concomitant use. Dopamine has an inhibitory effect on melatonin release, while melatonin also inhibits dopamine release. This should be taken into account when considering the use of melatonin in Parkinson’s disease. On the contrary, use of melatonin may offer therapeutic advantages for schizophrenia and tardive dyskinesia. The interaction between norepinephrine and melatonin exhibits diurnal variability, with norepinephrine promoting arousal and inhibiting daytime melatonin secretion. Melatonergic neurons also exert a specific protective influence on cholinergic neurons. Interaction between the histaminergic and melatonergic systems is significant, particularly in association with immunity, sleep, and circadian rhythm. Novel ligands with dual-acting properties, interacting with both the histaminergic and melatonergic systems are investigated. Currently, there is a limited number of approved melatonergic agents that primarily demonstrate positive effects in addressing insomnia and depression. However, there is considerable potential in studying new agents that target both the melatonergic and other neurotransmitter systems, which alleviate various conditions, including neurodegenerative diseases, dementia, autoimmune diseases, allergic diseases, epilepsy, and other neuropsychiatric disorders. The ongoing process of developing and evaluating new ligands selectively targeting the melatonergic system remains crucial in understanding the complex relationship between these systems.

AIM:This study aimed to reveal the current status of the literature on rational prescribing training in undergraduate medical education.METHODS:This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. An online search using 50 keywords in four databases was performed to access the studies published between 2008 and 2020. Specific features of the training such as aims or objectives of teaching, methods or model, and evaluation of effectiveness were extracted. Kirkpatrick levels were used to evaluate the effectiveness of teaching.RESULTS:Of 74 studies included in the full review, 16 (21.6%) of them reported the use of WHO 6-Step Model for Rational Prescribing in their educational interventions. In terms of effectiveness, only two of the studies investigated changes in learner behavior in the context for which they are being trained, and only one study showed the effect of training on patient outcomes.CONCLUSION:The evidence on the effectiveness of rational prescribing training has been presented mostly by using student satisfaction surveys and test of knowledge and skills. A higher level of evidence such as patient outcomes of the training needs to be reported.

Objective: This study was planned to determine the effects of carob use on puberty because of the observation of early puberty or pubertal variants due to the long-term use of carob in our clinic. Methods: Forty-eight Wistar albino rats, on postnatal day 21, were assigned into two groups female (n=24) and male (n=24). Groups were divided into four groups Control, and Carob-150, Carob-300, and Carob-600. Ceratonia siliqua L. extract was given to rats in a 0.5% carboxymethylcellulose (CMC) solution. CMC (0.5%) was given to the control, Ceratonia siliqua L. extract was given 150 mg/kg/day to the Carob-150, 300 mg/kg/day to the Carob-300, 600 mg/kg/day to the Carob-600 by oral gavage. The treatments were performed once daily until the first sign of puberty. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, total testosterone, leptin, glutathione, glutathione peroxidase (GPx), and malondialdehyde were measured by commercial rat-specific ELISA kits. Testis, uterus and ovarian tissue were examined histologically. Results: The median time of preputial separation in male rats was 38th, 31st, 31st, and 31st days in the Control, Carob-150, Carob-300, and Carob-600 groups, respectively (p=0.004). The median day of vaginal opening day was the 39th, 31st, 34th, and 31st days in the Control, Carob-150, Carob-300, and Carob-600 groups, respectively (p=0.059). FSH, LH, testosterone (male), estradiol (female) and leptin levels of the groups were similar. However, GPx levels were higher in male and female animals given C. siliqua extract compared to the Control (male p=0.001 and female p=0.008). Testicular and ovarian tissues were concordant with the pubertal period in all groups. As the dose of Ceratonia siliqua extract increased, it induced spermatogenesis and spermiogenesis, causing abnormal changes, such as ondulation in the basement membrane, capillary dilatation, and increased congestion in males. In females, edema in the medulla gradually increased with increased dosage, and granulosa cell connections were separated in Carob-300 and Carob-600 groups. Conclusion: This study demonstrated that C. siliqua caused early puberty and increased spermiogenesis and folliculogenesis. Antioxidant mechanisms were impaired with increasing dose, possibly leading to tissue damage at high doses.

Aim: Losartan, a drug in the angiotensin receptor blocker (ARB) family, is the substrate of the Multi Drug Resistance-1 (MDR1) drug-efflux protein encoded by the ABCB1 gene. This study seeks to investigate the MDR1 gene polymorphism and losartan concentration in order to identify drug resistance in patients presenting to the emergency department (ED) with a hypertensive episode while having losartan treatment. Method: The patient cohort was comprised of 50 individuals presenting with a hypertensive episode while under losartan treatment. The control cohort included 50 patients whose blood pressure was regulated while receiving losartan treatment and who were admitted to the ED for reasons other than hypertensive episode. Allele-specific PCR analysis was carried out in order to determine the frequencies of the G2677T/A, C3435T and C1236T genotypes. Plasma losartan and EXP3174 levels of the patients were calculated using tandem mass spectrometry Findings: The frequencies of GG, GT, GA, TA and TT genotypes did not differ significantly between the cohorts in G2677T/A single nucleotide polymorphism (SNP) (p>0.05), whereas those of C3435T TT and C1236T CT genotypes yielded a significant difference between the patient and control cohorts (p<0.05). Besides, no significant difference was evident between G2677T/A, C3435T and C1236T genotypes with respect to plasma losartan/EXP3174 concentration (p>0.05). Conclusion: We provided clinical evidence that hypertensive episodes occurred more frequently in C3435T TT and less frequently in C1236T CT. However, no significant correlation was established between plasma losartan, EXP3174 concentration and G2677T/A, C3435T, and C1236T genotypes. Keywords: Losartan, MDR1, Genetic polymorphism, EXP3174, Hypertension

The chronobiological effects of melatonin which is mainly secreted by the pineal gland in the central nervous system are thoroughly known. However, beyond this knowledge, the role of melatonin in the physiology and pathologies of the gastrointestinal system (GIS) is also noteworthy. Melatonin is synthesized in large quantities from enterochromaffin cells in the GIS, independent from a photoperiodic rhythm. Melatonin synthesized from these cells shows widespread effects on peripheral tissues by binding to MT1 / MT2 receptors. Melatonin, as is well known, has a free radical scavenging role, except for receptor-dependent effects. It has also been reported to have regulatory roles on GIS motility and visceral sensation. The role of melatonin in gastrointestinal pathologies has being investigated for a long period, especially in esophagitis, gastric mucosal injury, peptic ulcer, irritable bowel syndrome, inflammatory bowel diseases, and necrotizing enterocolitis. In this context, the protective effects of melatonin in the GIS are markedly drawing attention nowadays. Yet until recently, melatonin itself and its agonists have only found clinical use in jet lag, insomnia, and depression accompanied by sleep deprivation. However, new findings are promising regarding the therapeutic potential of melatonin for GIS pathologies. This review reveals the role of melatonin in GIS physiology and pathologies in the light of the recent literature.

Dry eye is both a common symptom and a disease. It is known that the ophthalmic emulsion of the immunomodulator cyclosporine-A (Cyc-A) has a positive effect on this condition but its’ absorption to intraocular tissues is limited. Nanosuspension is a drug formulation that aims to increase the bioavailability. The aim of this study was to develop a Cyc-A nanosuspension formulation for a better intraocular absorption via ocular delivery and to investigate the effectiveness of the formulation by comparing it with two marketed ophthalmic emulsions (Restasis® and Depores®). Two type of Cyc-A loaded Eudragit S100 nanosuspension (A and B) were prepared. Drug formulations were applied to both eyes of 20 male Albino New Zealand rabbits with an interval of 12 hours for 14 days. In vitro drug release was tested using a dialysis sac and quantitative analysis was performed by HPLC for evaluating Cyc-A amounts in all formulations. Although all four formulations had similar particle size and polydispersity indexes, nanosuspension B which had a positive zeta potential value, had released more Cyc-A than other formulations. It was showed that Cyc-A loaded nanosuspension formulations which had good ocular tolerability could be a better alternative to commercial formulations for the treatment of dry eye. The nanosuspensions have ideal mean particle size range with a positive surface charge for ophthalmic applications of Cyc-A.