A High Sensitivity CMUT-Based Passive Cavitation Detector for Monitoring Microbubble Dynamics During Focused Ultrasound Interventions.

Tracking and controlling microbubble (MB) dynamics in the human brain through acoustic emission monitoring during transcranial focused ultrasound therapy (tFUS) is critical for attaining safe and effective treatments. The low-amplitude MB emissions have harmonic and ultra-harmonic components, necessitating a broad bandwidth and low-noise system for monitoring transcranial MB activity. Capacitive Micromachined Ultrasonic Transducers (CMUTs) offer high sensitivity and low noise over a broad bandwidth, especially when they are tightly integrated with electronics, making them a good candidate technology for monitoring the MB activity through human skull. In this study, we designed a 16-channel Analog Front-end Electronics (AFE) with a low-noise transimpedance amplifier (TIA), a band-gap reference circuit, and an output buffer stage. To assess AFE performance and ability to detect MB acoustic emission, we combined it with a commercial CMUT array. The integrated system has 12.3 - 61.25 mV/Pa receive sensitivity with 0.085 - 0.23 mPa/ √ Hz minimum detectable pressure up to 3 MHz for a single element CMUT with 3.78 mm2 area. Experiments with free microbubbles in a microfluidic channel demonstrate that our system is able to capture key spectral components of MBs' harmonics when sonicated at clinically relevant frequencies (0.5 MHz) and pressures (250 kPa). Together our results demonstrate that the proposed CMUT system can support the development of novel passive cavitation detectors to track MB activity for attaining safe and effective FUS treatments.

A 1.11 mm2 IVUS SoC with ±50°-Range Plane Wave Transmit Beamforming at 40 MHz.

Intravascular ultrasound (IVUS) imaging catheters are significant tools for cardiovascular interventions, and their use can be expanded by realizing IVUS imaging guidewires and microcatheters. The miniaturization of these devices creates challenges in SNR due to the need for higher frequencies to provide adequate resolution. An integrated IVUS system with transmit beamforming can mitigate these limitations. This work presents the first practical highly integrated system-on-a-chip (SoC) with plane wave transmit beamforming at 40 MHz for IVUS on guidewire or microcatheters. The front-end circuitry has a 20-channel ultrasound transmitter (Tx) and receiver (Rx) array interfaced with a capacitive micromachined ultrasound transducer (CMUT) array. During each firing, all 20 Tx are excited with the same analog delay with respect to each other, which can be continuously adjusted between ~0 and 10 ns in two directions, generating a steerable plane wave in a range of ±/-50° for a phased array at 40 MHz. The unit delays are generated via a voltage-controlled delay line (VCDL), which only needs two external controls, one tuning the unit delay and the other determining the steering direction. The SoC is fabricated using a 180-nm high-voltage (HV) CMOS process and features a slender active area of 0.3 mm × 3.7 mm. The proposed SoC consumes 31.3 mW during the receiving mode. The beamformer's functionality and the SoC's overall performance were validated through acoustic characterization and imaging experiments.

CMUT as a Transmitter for Microbubble-Assisted Blood-Brain Barrier Opening.

Focused ultrasound (FUS) combined with microbubbles (MBs) has emerged as a promising strategy for transiently opening the blood-brain barrier (BBB) to enhance drug permeability in the brain. Current FUS systems for BBB opening use piezoelectric transducers as transmitters and receivers. While capacitive micromachined ultrasonic transducers (CMUTs) have been suggested as a FUS receiver alternative due to their broad bandwidth, their capabilities as transmitters have not been investigated. This is mainly due to the intrinsic nonlinear behavior of CMUTs which complicates the detection of MB generated harmonic signals and their low pressure output at FUS frequencies. Various methods have been proposed to mitigate CMUT nonlinearity; however, these approaches have primarily targeted contrast enhanced ultrasound imaging. In this study, we propose the use of polyphase modulation (PM) technique to isolate MB emissions when CMUTs are employed as transmitters for BBB opening. Our calculations for a human scale FUS system with multiple CMUT transmitters show that 10 kPa peak negative pressure at 150 mm focal distance will be sufficient for MB excitation for BBB opening. Experimental findings indicate that this pressure level can be easily generated at 400-800 kHz using a readily available CMUT. Furthermore, more than 50 dB suppression of the fundamental harmonic signal is obtained in free field and transcranial hydrophone measurements by processing receive signals in response to phase modulated transmit waveforms. In-vitro validation of PM is also conducted using Definity MB flowing through a tube phantom. MB-filled tube phantoms show adequate nonlinear signal isolation and SNR for MB harmonic detection. Together our findings indicate that PM can effectively mitigate CMUT harmonic generation, thereby creating new opportunities for wideband transmission and receive operation for BBB opening in clinical and preclinical applications.

Single-scan ultrafast laser inscription of waveguides in IG2 for type-I and type-II operation in the mid-infrared.

We demonstrate, for the first time to our knowledge, single-scan ultrafast laser inscription and performance of mid-infrared waveguiding in IG2 chalcogenide glass in the type-I and type-II configurations. The waveguiding properties at 4550 nm are studied as a function of pulse energy, repetition rate, and additionally separation between the two inscribed tracks for type-II waveguides. Propagation losses of ∼1.2 dB/cm in a type-II waveguide and ∼2.1 dB/cm in a type-I waveguide have been demonstrated. For the latter type, there is an inverse relation between the refractive index contrast and the deposited surface energy density. Notably, type-I and type-II waveguiding have been observed at 4550 nm within and between the tracks of two-track structures. In addition, although type-II waveguiding has been observed in the near infrared (1064 nm) and mid infrared (4550 nm) in two-track structures, type-I waveguiding within each track has only been observed in the mid infrared.

An Adaptive Element-Level Impedance-Matched ASIC With Improved Acoustic Reflectivity for Medical Ultrasound Imaging.

This paper presents an active impedance matching scheme that tries to optimize electrical power transfer and acoustic reflectivity in ultrasound transducers. Leveraging negative capacitance-based impedance matching would potentially improve the bandwidth and electrical power transfer while minimizing acoustic reflection of transducer elements and improve uniformity while reducing acoustic crosstalk of transducer arrays. A 16-element transceiver front-end is designed which employs an element-level active capacitive impedance cancellation scheme using an element-level negative impedance converter. The ASIC fabricated in 180-nm HVBCD technology provides high-voltage pulses up to 60 V consuming 3.6 mW and occupying 2.5 mm2. The front-end ASIC is used with a 1-D capacitive micromachined ultrasonic transducer (CMUT) array and its acoustical reflectivity reduction and imaging capabilities have successfully been demonstrated through pulse-echo measurements and acoustic imaging experiments.

Towards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound.

Brain tumors are particularly challenging malignancies, due to their location in a structurally and functionally distinct part of the human body - the central nervous system (CNS). The CNS is separated and protected by a unique system of brain and blood vessel cells which together prevent most bloodborne therapeutics from entering the brain tumor microenvironment (TME). Recently, great strides have been made through microbubble (MB) ultrasound contrast agents in conjunction with ultrasound energy to locally increase the permeability of brain vessels and modulate the brain TME. As we elaborate in this review, this physical method can effectively deliver a wide range of anticancer agents, including chemotherapeutics, antibodies, and nanoparticle drug conjugates across a range of preclinical brain tumors, including high grade glioma (glioblastoma), diffuse intrinsic pontine gliomas, and brain metastasis. Moreover, recent evidence suggests that this technology can promote the effective delivery of novel immunotherapeutic agents, including immune check-point inhibitors and chimeric antigen receptor T cells, among others. With early clinical studies demonstrating safety, and several Phase I/II trials testing the preclinical findings underway, this technology is making firm steps towards shaping the future treatments of primary and metastatic brain cancer. By elaborating on its key components, including ultrasound systems and MB technology, along with methods for closed-loop spatial and temporal control of MB activity, we highlight how this technology can be tuned to enable new, personalized treatment strategies for primary brain malignancies and brain metastases.

Sugammadex Improves Neuromuscular Function in Patients Receiving Perioperative Steroids.

CONTEXT: Sugammadex has steroid-encapsulating effect. AIM: This study was undertaken to assess whether the clinical efficacy of sugammadex was altered by the administration of steroids. SETTING AND DESIGN: Sixty patients between 18 and 60 years of age with the American Society of Anesthesiologists I-IV and undergoing elective direct laryngoscopy/biopsy were included in this study. MATERIALS AND METHODS: Patients were assigned to two groups based on the intraoperative steroid use: those who received steroid (Group S) and who did not (Group C). After standard general anesthesia, patients were monitored with the train of four (TOF) monitoring. The preferred steroid and its dose, timing of steroid administration, and TOF value before and after sugammadex as well as the time to recovery (TOF of 0.9) were recorded. STATISTICAL ANALYSIS USED: SPSS software version 17.0 was used for statistical analysis. RESULTS: There is no statistically significant difference between groups in terms of age, gender, preoperative medication use, and TOF ratio just before administering sugammadex. The reached time to TOF 0.9 after sugammadex administration was significantly shorter in Group S than Group C (P < 0.05). A within-group comparison in Group S showed no difference in TOF ratio immediately before sugammadex as well as the dose of sugammadex in those who received prednisolone; time to TOF 0.9 was higher in prednisolone receivers as compared to dexamethasone receivers (P < 0.05). CONCLUSION: In patients receiving steroids, and particularly dexamethasone, an earlier reversal of neuromuscular block by sugammadex was found, in contrast with what one expect. Further studies are required to determine the cause of this effect which is probably due to a potential interaction between sugammadex and steroids.

Kinematic analysis of scapular movements in patients with facioscapulohumeral muscular dystrophy.

The purpose of this study is to evaluate scapular movements by the three-dimensional electromagnetic system during shoulder elevation in FSHMD patients, and to compare the results with healthy individuals. 10 patients with FSHMD and 10 healthy individuals were included in the study. Scapular anterior-posterior tilt, upward-downward rotation and internal-external rotation at 30°, 60° and 90° were evaluated using the three-dimensional electromagnetic system during the elevation of the upper limbs in the scapular plane. Humerothoracic elevation levels on the dominant and non-dominant sides were found to be lower in the patients than healthy individuals (p < .001). Both scapula were rotated downwards at 30° (dominant/non-dominant p < .001) and 60° (dominant p = .009, non-dominant p = .04) of humerothoracic elevation, the scapula was rotated internally at 30° of humerothoracic elevation on the non-dominant side (p = .03), and the scapula was tilted posteriorly at 90° of humerothoracic elevation on the non-dominant side (p = .009) in patients. These existing abnormal patterns of the scapula in the patients increase the risk of impairment, pain, impingement and instability especially in the activities that require arm elevation. It is thought that physiotherapy approaches should first be emphasized to improve scapular stabilization and strengthening exercises should then be performed for the shoulder girdle muscles.

Impact of physical activity on patient self-reported outcomes of lifelong premature ejaculation patients: Results of a prospective, randomised, sham-controlled trial.

Previous studies have investigated whether physical activity increases serotonin hormone levels. Serotonin receptor dysfunction is one of the frequently accused factors of premature ejaculation (PE). Nevertheless, no studies up to date have demonstrated that the association between physical activity and premature ejaculation. We aimed to investigate the relationship between physical activity and PE and determine whether moderate physical activity might delay ejaculation time or be an alternative treatment for PE. A total of 105 patients diagnosed with PE were enrolled in this study. Of the patients, 35 were treated with dapoxetine, (30 mg) on demand (Group 1), 35 performed moderate physical activities (Group 2), and 35 performed minimal physical activity (Group 3-sham). Demographic characteristics, metabolic equivalents (MET), premature ejaculation diagnostic tool (PEDT) and intravaginal ejaculatory latency time (IELT) were recorded. There were no significant differences among three groups in terms of age, BMI, MET, PEDT or IELT before treatment. At the end of the study, there was significant decrease in PEDT scores, and increase in IELT in groups 1 and 2 as compared to Group 3. In conclusion, a moderate physical activity longer than 30 min at least 5 times a week leads to ejaculation delay, and appears as an alternative to dapoxetine on demand for the treatment of PE.

Visualization of Superficial Cerebral Lesions Using a Smartphone Application.

AIM: Accurate localizations of cerebral lesions ensure good surgical outcomes and minimize intraoperative complications. Currently, microscope-integrated neuronavigation systems compensate these requirements. Since these units are expensive and large, the need to create more practical and portable systems in this "smart" century has become apparent. MATERIAL AND METHODS: The See-Through Camera smartphone application (app) is a photography app that penetrates the existing background picture and merges this with a camera image on the smartphone display. This app was applied to neurosurgery for visualization of the projection of the tumors over head in 20 patients. App accuracy was tested according to neuronavigation system. RESULTS: Precision of the app was evaluated according to the superposition ratio of the tumor image drawn by the navigation system with the tumor picture on the smartphone display. This ratio was 40%-100% in 16 (80%) patients and below 40% as an unfavorable result in the rest of the patients. CONCLUSION: Basic rationality of this app can provide the basis of future pocket navigation systems in terms of its design and principles.

A Macro-Anatomical Investigation of the Some Skull Bones of Nehring's Blind Mole Rats (Spalacidae: Nannospalax nehringi).

This study was aimed to demonstrate the specific anatomical features of the skull bones of Nehring's blind mole rats. Eight skulls, belonging to animals of both sexes, were used. The occipital squama contributed to the formation of the caudal portion of the skull roof. The foramen magnum was quite large. The external occipital crest was present only in the males. The parietal bones formed the middle portion of the skull roof together with the well-developed inter-parietal bones. The zygomatic process of the temporal bone formed the zygomatic arch by extending to the temporal process of the zygomatic bone. The zygomatic process of the frontal bone and the frontal process of the zygomatic bone laterally bordered the orbit. There was a single septal process of the nasal bone. Each ramus of the mandibula had four processes. The mandibular ramus had an angular process on its caudal rim, which extended dorsolaterally. The dorsal free end of the mandibular ramus possessed a coronoid process. In the back, there were two other processes, situated medially and laterally. The medially situated process was referred to as a condylar process, and the laterally situated process was referred to as an alveolar process. The alveolar process detected on the mandibular ramus has not been reported in any rodent species, other than those of the family Spalacidae. Blind mole rats can be a real eye-opener for evolutionary science. The burrowing rodents are key to answering a controversial question about how new species arise.

Generalized CNS arousal: An elementary force within the vertebrate nervous system.

Why do animals and humans do anything at all? Arousal is the most powerful and essential function of the brain, a continuous function that accounts for the ability of animals and humans to respond to stimuli in the environment by producing muscular responses. Following decades of psychological, neurophysiological and molecular investigations, generalized CNS arousal can now be analyzed using approaches usually applied to physical systems. The concept of "criticality" is a state that illustrates an advantage for arousal systems poised near a phase transition. This property provides speed and sensitivity and facilitates the transition of the system into different brain states, especially as the brain crosses a phase transition from less aroused to more aroused states. In summary, concepts derived from applied mathematics of physical systems will now find their application in this area of neuroscience, the neurobiology of CNS arousal.

Evaluation of hematological markers in minor head trauma in the emergency room.

INTRODUCTION: A rule exists regarding the use of computed tomography (CT) for patients presenting to the emergency department with head trauma and a Glasgow coma score (GCS) of 15; however, it can be difficult to make this decision due to overcrowded emergency rooms or exaggerated patients complaints. We evaluated patients who presented to the emergency room with minor head trauma, and we aimed to investigate the relationship between brain pathology on CT and hematological markers in order to find markers that help us identify brain pathology in patients with a GCS of 15. METHODS: This retrospective study included 100 patients with pathologies present on their CT scans and a control group consisting of 100 patients with a normal CT. All data obtained from this study were recorded and evaluated using "Statistical Package for Social Sciences for Windows 20" program. Parametric tests (independent samples test) were used with normally distributed data, while non-parametric tests (Mann-Whitney U test) were used with non-normally distributed data. A p ≤ 0.05 was considered significant. FINDING: When we divided the cases into two groups based on the presence of pathologies on CT scan, we determined that there were significant differences between the groups in terms of white blood cell (WBC), hemoglobin (Hb), mean platelet volume (MPV), neutrophil (neu), troponin T, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). When differentiating the patients that had brain pathologies on CT scan from patients that had normal CT scans, the troponin T cut-off value of 6.16 lead to 90 % specificity, and setting the NLR cut-off value at 4.29 resulted in a specificity of 90 %. CONCLUSION: MPV, NLR, and troponin T can be used as parameters that indicate brain pathologies on CT scans of patients presenting to the emergency department with isolated minor head trauma and GCS of 15 when the necessity of a CT scan is otherwise unclear.

Serum human epididymis protein 4 can be a useful tumor marker in the differential diagnosis of adnexal masses during pregnancy: a pilot study.

PURPOSE: The purpose of this study was to evaluate serum concentrations of human epididymis protein 4 (HE4) and cancer antigen 125 (CA 125) in healthy women and their pregnant counterparts to determine the influence of pregnancy on these biomarkers. MATERIALS AND METHODS: Serum concentrations of CA 125 and HE4 were measured in 27 healthy non-pregnant women and 26 healthy pregnant women in the first and second trimesters. RESULTS: Higher concentration of CA 125 was found in pregnants than in non-pregnant women (p = 0.002). There was no difference in CA 125 concentrations between first and second trimesters (p = 0.13). Serum HE4 concentration was not different in pregnant group compared to non-pregnant women (p = 0.510). Likewise, no difference was found in HE4 levels between the trimesters (p = 0.485). There was a positive correlation between increasing parity and CA 125 (p = 0.023), but not HE4 (p = 1.0). CONCLUSION: HE4 serum biomarker is unaffected by pregnancy status and may be useful for evaluation of doubtful pelvic masses in pregnancy. Contrarily, increased serum levels of CA 125 could yield increased number of false-positive results.

The Relationship between Acidic Urinary pH and Overactive Bladder; Alkalization of Urine Improves the Symptoms of Overactive Bladder.

BACKGROUND: To determine association between urine pH and OAB symptoms and to determine if urinary alkalization improves overactive bladder (OAB) symptoms. METHODS: 659 patients with OAB were enrolled in this study between June 2012 and May 2014. 329 patients (group 1) were included in the final analysis. 201 adults were used as a control group (group 2). 24-hour urinary pH and the validated Turkish version of the OAB-V8 questionnaire were performed in patients. A 24-hour urine pH <6.2 was considered acidic urine. In the second part, a diet program was performed for 4 weeks in 30 participants. Urine pH values and OAB-V8 scoring results were recorded before the diet program and 2 and 4 weeks after the diet program. RESULTS: Acidic urinary pH was determined in 61.4% of patients with OAB. There was a significant association between the presence of acidic urine and OAB. Also, the OAB-V8 scores of patients were significantly higher in patients with acidic urine than nonacidic urine. OAB-V8 scores of patients showed statistically significant improvement after diet therapy (17.87 ± 6.52 vs. 10.43 ± 7.17; p < 0.001). CONCLUSIONS: We found that acidic urinary pH was closely associated with OAB, and alkalization of urine improved lower urinary tract symptoms. We suggest that urinary pH should be considered as a parameter in treatment planning of patients with OAB.

Is methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphism related with varicocele risk?

Varicocele is one of the main reasons for male infertility the exact aetiology of which remains unclear. Methylenetetrahydrofolate reductase (MTHFR) is important for DNA synthesis and methylation, which has a key role during spermatogenesis. Numerous literature suggests that the MTHFR polymorphism may be genetic risk factors for male infertility. In this study, we evaluated C677T and A1298C MTHFR gene polymorphism frequency in patients with varicocele and normal men. A total of 107 varicocele patients and 109 fertile healthy individuals were included. Genotyping of the MTHFR gene in C677T and A1298C base pairs carried out by using real-time PCR technique and afterwards, the statistical analysis accomplished. There is a statistical difference for the frequency of 1298AA genotype in patients with varicocele compared with normal controls (P = 0.0051, OR = 2.2750). Instead, subsequently, 1298/A allel frequency in patient group was significantly higher in comparison with control group (P = 0.0174). According to our results, 1298AA genotype in MTHFR gene raises the risk of varicocele approximately 2.3 times more compared with men carrying other genotypes. The results show that genetic factors have an important role in the molecular basis of varicocele.

The effect of ovariectomy on the skin flap viability and myeloperoxidase levels.

OBJECTIVES: Estrogen could affect the rate and quality of wound healing in skin. We aimed to investigate the effects of ovariectomy on skin flap viability and myeloperoxidase (MPO) levels in a rat model. BACKGROUND: Estrogens have many important beneficial and protective roles in skin that they improve collagen content and quality, maintain skin thickness and enhance vascularization. It has been shown that estrogen supplementation accelerates cutaneous wound healing in elderly patients. METHODS: Forty-eight cycling female Wistar albino rats were randomly divided into three groups (n = 16); ovariectomy (Group 1), sham (Group 2), and control (Group 3). Rats were subjected to bilateral ovariectomy in the Group 1, and only laparotomy in the Group 2. Twenty-one days later in the Group 1 and 2, a dorsal caudally based skin flap elevation was done. In the Group 3, the rats had a dorsal skin flap without any surgical intervention. Ten days later, the flaps were harvested for histopathologic examination and biochemical analyses. RESULTS: The rats in the Group 1 had significantly larger necrotic area and lower flap viability than in the Group 2 and 3 (p<0.05). Histopathologic examination showed that necrotic flap regions contained muscle necrosis with an abundant neutrophil infiltration, and severe edema in the Group 1. The MPO activity in the distal of skin flaps was significantly higher in the Group 1 compared to the Group 2 and 3 (p<0.05). CONCLUSION: This study shows that ovariectomy has deleterious effects on skin flap viability in a rat model (Tab. 1, Fig. 6, Ref. 44).

Comparison of anaesthetic cost in open and laparoscopic appendectomy.

CONTEXT: Appendectomy is generally conducted as open or by laparoscopic surgical techniques under general anesthesia. AIMS: This study aims to compare the anesthetic costs of the patients, who underwent open or laparoscopic appendectomy under general anesthesia. SETTINGS AND DESIGN: The design is retrospective and records of 379 patients who underwent open or laparoscopic appendectomy under general anesthesia, falling under the category of I-III risk group according to the American Society of Anesthesiologists (ASA) classification between the years 2011 and 2013, and aged 18-77. SUBJECTS AND METHODS: Open (Group I) or laparoscopic (Group II) appendectomy operation under general anesthesia were evaluated retrospectively by utilizing hospital automation and anesthesia observation records. This study evaluated the anesthesia time of the patients and total costs (Turkish Lira ₺, US dollar $) of anesthetic agents used (induction, maintenance), necessary medical materials (connecting line, endotracheal tube, airway, humidifier, branule, aspiration probe), and intravenously administered fluids were evaluated. STATISTICAL ANALYSIS USED: We used Statistical Package for the Social Sciences software (SPSS version 17.0) for statistical analysis. RESULTS: Of the patients, 237 were males (62.53%) and 142 were females (37.47%). Anesthesia time limits were established as 70.30 ± 30.23 minute in Group I and 74.92 ± 31.83 minute in Group II. Mean anesthesia administration cost per patient was found to be 78.79 ± 30.01₺ (39.16 ± 14.15$) in Group I and 83.09 ± 26.85₺ (41.29 ± 13.34$) in Group II (P > 0.05). A correlation was observed between cost and operation times (P = 0.002, r = 0.158). CONCLUSIONS: Although a statistical difference was not established in this study in terms of time and costs in appendectomy operations conducted as open and laparoscopically, changes may occur in time in market conditions of drugs, patent rights, legal regulations, and prices. Therefore, we believe that it would be beneficial to update and revise cost analyses from time to time.

Melatonin prevents retinal oxidative stress and vascular changes in diabetic rats.

PURPOSE: To evaluate the role of melatonin, an antioxidant agent, in diabetic oxidative stress and vascular damage. METHODS: Diabetes was induced in 21 male Wistar rats by intraperitoneal (IP) administration of streptozotocin and then the rats were equally and randomly allocated to diabetic, melatonin, and vehicle groups. Seven healthy normal rats with similar features comprised the control group as the fourth group. All animals were followed for 12 weeks. The melatonin group received IP melatonin daily and the vehicle group received 2.5% ethanol IP at the last month. At the end of 12 weeks, the rats were killed and retinas were harvested. The retinas were investigated for the existence of hypoxia-inducible factor 1-α (HIF-1α), vascular endothelial growth factor A (VEGF-A), and pigment epithelium-derived factor (PEDF) by ELISA. Retinal oxidative stress is quantitated by measuring nitrotyrosine and malondialdehyde levels. Retinal immunohistochemistry with antibody against CD31 antigen was carried out on retinal cross-sections. For statistics, ANOVA test was used for multiple comparisons. RESULTS: Hyperglycemia increased retinal oxidation as measured through levels of nitrotyrosine and malondialdehyde. Diabetic retinas are also associated with abnormal vascular changes such as dilatation and deformation. HIF-1α, VEGF-A, and PEDF were all increased because of diabetic injury. Melatonin showed a potential beneficial effect on retinopathy in diabetic rats. It decreased retinal nitrotyrosine and malondialdehyde levels, showing an antioxidative support. The vasculomodulator cytokines are decreased accordingly by melatonin therapy. Melatonin normalized retinal vascular changes as well. CONCLUSION: Melatonin may show some advantage on diabetic vascular changes through decreasing oxidative stress and vessel-related cytokines.