Photocoagulation Up to Ora Serrata in Diabetic Vitrectomy to Prevent Recurrent Vitreous Hemorrhage

Purpose@#To evaluate the role of performing photocoagulation up to ora serrata during vitrectomy in preventing recurrent vitreous hemorrhage (VH) in patients undergoing pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). @*Methods@#This retrospective, nonrandomized study included 60 eyes from 60 patients who had undergone PPV for VH due to PDR. These patients were divided into two groups: group 1, those who underwent photocoagulation up to ora serrata using the scleral indentation technique during surgery; and group 2, those who did not undergo scleral indentation when photocoagulation and underwent photocoagulation up to vortex veins. Their hospital records were analyzed to investigate the recurrence rate of VH, the time until recurrence of VH after surgery, logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) measured before surgery and at 1, 2, and 3 years after surgery, and the occurrence of complications such as neovascular glaucoma (NVG) during follow-up. @*Results@#Group 1 exhibited lower recurrence rate of VH (2 of 30 [6.7%] vs. 10 of 30 [33.3%], p = 0.01) and lower occurrence of postoperative NVG (2 of 30 [6.7%] vs. 8 of 30 [26.7%], p = 0.038) compared with group 2. There were no statistically significant differences in logMAR BCVA measured at 1, 2, and 3 years between the two groups (at 1 year: 0.54 ± 0.43 vs. 0.54 ± 0.44, p = 0.954; at 2 years: 0.48 ± 0.47 vs. 0.55 ± 0.64, p = 0.235; at 3 years: 0.51 ± 0.50 vs. 0.61 ± 0.77, p = 0.200). Logistic regression analysis showed that among several factors that could affect recurrence rate of VH, only range of photocoagulation performed was a statistically significant factor (odds ratio, 0.119; 95% confidence interval, 0.022–0.659; p = 0.015). @*Conclusions@#Photocoagulation treatment over a wider range with scleral indentation could be a beneficial adjunct procedure for preventing postoperative recurrent VH following diabetic vitrectomy.

Inter-eye Comparison of Peripapillary Choroidal Thickness in Patients with Treatment-naïve Unilateral Open-angle Glaucoma

Purpose@#We investigated the relationship between optic nerve damage and peripapillary choroidal thickness in patients with treatment-naïve primary open-angle glaucoma. @*Methods@#Peripapillary choroidal thicknesses of 78 eyes of 39 patients with primary open-angle glaucoma were measured on 360° scans of enhanced-depth optical coherence tomography images using the inbuilt manual segmentation function. Inter-eye peripapillary choroidal thicknesses were compared and factors associated with glaucoma were analyzed. @*Results@#Eyes with primary open-angle glaucoma exhibited thinner peripapillary choroidal thickness (133.2 ± 52.1 vs. 144.1 ± 53.0 μm; p < 0.001), higher intraocular pressure (16.7 ± 3.9 vs. 15.4 ± 2.6 mmHg; p = 0.005), thinner corneal thickness (523.8 ± 32.5 vs. 527.6 ± 35.0 μm; p = 0.030), and thinner retinal nerve fiber layer (72.2 ± 13.7 vs. 89.3 ± 13.1 μm; p < 0.001), compared with healthy fellow eyes. On multivariate, conditional, logistic regression analysis, thinner peripapillary choroidal thickness (odds ratio [OR] 0.910, 95% confidence interval [CI] 0.834-0.993; p = 0.035) and higher intraocular pressure (OR 3.368, 95% CI 1.285-8.828; p = 0.014) were significantly associated with glaucoma. @*Conclusions@#Thinner peripapillary choroid and higher intraocular pressure were significantly associated with glaucoma in patients with unilateral primary open-angle glaucoma, suggesting that poor perfusion around the optic nerve head may be associated with glaucoma pathogenesis.

Measuring Defocus Curves of Monofocal, Multifocal and Extended Depth-of-focus Intraocular Lenses Using Optical Bench Test

PURPOSE: To determine the through-focus optical bench test performance of monofocal, bifocal, and extended depth-of-focus intraocular lenses (IOLs), and to measure their defocus curves.METHODS: A model eye was placed on an optical bench to test three different IOLs (TECNIS ZXR00, ZMB00, and ZCB00; Abbott Medical Optics, Santa Ana, CA, USA). The focus was changed by inserting trial lenses from +1.00 diopters to −4.00 diopters, in increments of +0.25 diopters. The 1951 United States Air Force Resolution chart was used to determine the quality of the images. The degree of similarity with reference images was given by the cross-correlation coefficient, and defocus curves were drawn and compared.RESULTS: Bifocal IOLs showed lower image quality with the addition of minus diopter trial lenses, but showed good image quality at near distance. Bifocal IOLs also showed a ‘double peak’ in their defocus curve. Monofocal IOLs showed a lower image quality and cross-correlation coefficient with addition of lower-diopter trial lenses. The extended depth of focus IOLs showed a single peak in their defocus curve, but had a wider range of diopters and better image quality than monofocal IOLs.CONCLUSIONS: Bifocal IOLs showed a double peak defocus curve, and extended depth of focus IOLs showed a wider diopter range and better image quality than monofocal IOLs.

Manual Preparation of Donor Lenticule Using Artificial Anterior Chamber for Descemet's Membrane Stripping Endothelial Keratoplasty

PURPOSE: To report a patient with a pseudophakic bullous keratopathy (PBK) who underwent Descemet's membrane stripping endothelial keratoplasty (DSEK) with manual preparation of the donor corneal graft.CASE SUMMARY: A 61-year-old female presented with visual disturbance in her right eye. Five months prior, she was treated with phacoemulsification and intraocular lens exchange surgery of the right eye, and a very severe corneal edema was revealed by slit-lamp examination. We diagnosed PBK and planned DSEK with manual preparation of a donor corneal graft because of the non-availability of a microkeratome or a femtosecond laser. After making the corneal graft using an artificial anterior chamber, crescent knife and cornea dissector, the keratoplasty proceeded using the graft. Three months after surgery, her graft was well-maintained on the right eye. The patient's visual acuity was 0.3, and the corneal endothelial cell count was 1,844/mm².CONCLUSIONS: Manual preparation of the donor corneal graft for DSEK is suitable as a second choice treatment method when the availability of surgical devices is limited.

Non-glaucomatous Retinal Nerve Fiber Layer Defect Associated with Paravascular Inner Retinal Defect

PURPOSE: To report a case of non-glaucomatous retinal nerve fiber layer (RNFL) defect associated with paravascular inner retinal defect (PIRD) in a patient with idiopathic epiretinal membrane (ERM).CASE SUMMARY: A 70-year-old male who was diagnosed with ERM in his right eye and pseudoexfoliative glaucoma in his left eye visited our clinic. His intraocular pressure was 14 mmHg in both eyes while using topical hypotensive medications in both eyes. His right eye showed no glaucomatous change of the optic disc head, and also no glaucomatous visual field defect on standard automated perimetry. Red-free fundus photography and swept-source optical coherence tomography showed an ERM and wedge-shaped RNFL defect starting from the PIRD, not the optic disc head. He was diagnosed with non-glaucomatous RNFL defect in the right eye and was told to stop using topical hypotensive medication for the right eye. After 2 years of discontinuing the medication, the IOP was within the normal range, the RNFL defect showed no progression, and the visual field remained stationary.CONCLUSIONS: A non-glaucomatous RNFL defect can develop in association with PIRD in patients with idiopathic ERM. Examinations for PIRD as well as evaluation of the optic disc head are therefore necessary in patients with ERM and RNFL defect.

Inter-eye Comparison of Peripapillary Choroidal Thickness in Patients with Treatment-naïve Unilateral Open-angle Glaucoma

Purpose@#We investigated the relationship between optic nerve damage and peripapillary choroidal thickness in patients with treatment-naïve primary open-angle glaucoma. @*Methods@#Peripapillary choroidal thicknesses of 78 eyes of 39 patients with primary open-angle glaucoma were measured on 360° scans of enhanced-depth optical coherence tomography images using the inbuilt manual segmentation function. Inter-eye peripapillary choroidal thicknesses were compared and factors associated with glaucoma were analyzed. @*Results@#Eyes with primary open-angle glaucoma exhibited thinner peripapillary choroidal thickness (133.2 ± 52.1 vs. 144.1 ± 53.0 μm; p < 0.001), higher intraocular pressure (16.7 ± 3.9 vs. 15.4 ± 2.6 mmHg; p = 0.005), thinner corneal thickness (523.8 ± 32.5 vs. 527.6 ± 35.0 μm; p = 0.030), and thinner retinal nerve fiber layer (72.2 ± 13.7 vs. 89.3 ± 13.1 μm; p < 0.001), compared with healthy fellow eyes. On multivariate, conditional, logistic regression analysis, thinner peripapillary choroidal thickness (odds ratio [OR] 0.910, 95% confidence interval [CI] 0.834-0.993; p = 0.035) and higher intraocular pressure (OR 3.368, 95% CI 1.285-8.828; p = 0.014) were significantly associated with glaucoma. @*Conclusions@#Thinner peripapillary choroid and higher intraocular pressure were significantly associated with glaucoma in patients with unilateral primary open-angle glaucoma, suggesting that poor perfusion around the optic nerve head may be associated with glaucoma pathogenesis.

Effects of Phosphatidylinositol 50 Intake on Memory and Learning Ability in Rats / 日本補完代替医療学会誌

Objective: Phosphatidylinositol (PI) has been suggested to have important functions in intracellular signal transduction and to be effective in improving brain function. However, its effects on memory and learning ability have not been elucidated. Therefore, in the present study, we aimed to clarify the effects of oral administration of 59% purified PI (PI 50) on memory and learning ability in rats. Methods: Wistar male rats were divided into four groups: (1) distilled water administration group, (2) 30 mg/kg PI 50 administration group, (3) 100 mg/kg PI 50 administration group, and (4) 300 mg/kg PI 50 administration group. Effects of oral administration of PI 50 on memory and learning ability were investigated using behavioral and molecular biological techniques. Result: In the learning and memory behavioral tests, the PI 50-administered group showed improvements in spatial memory and learning ability compared to the distilled water-administered group. Additionally, c-Fos- and BrdU-positive cells in the hippocampus increased significantly in the PI 50-administered group. The PI 50-administered group showed a significant increase in BDNF, PKC-α, and MAPK protein expression compared to the distilled water- administered group. Conclusion: These results indicate that PI 50 intake stimulates nerve cell activation and growth factor secretion in the hippocampus by activating the PKC-α and MAPK signal pathways, thus, facilitating the development and proliferation of nerve cells and may affect the enhancement of learning and memory ability. This study provides evidence that PI 50 may affect the enhancement of learning and memory ability.

Clinical Features and Surgical Outcomes of Primary Rhegmatogenous Retinal Detachment according to Age

PURPOSE: To investigate the clinical features and surgical outcomes of rhegmatogenous retinal detachment (RRD) requiring surgery according to age. METHODS: Medical records of patients who underwent surgery for primary RRD between January 2008 and March 2016 were reviewed retrospectively. Patients were classified into two groups according to age at diagnosis: the under-40 group and the over-40 group. The two groups were compared in terms of demographic features, ocular manifestation, operating methods, primary anatomical success rate, and visual outcome. RESULTS: One hundred and forty-four eyes from 144 patients were included. Mean subject age was 48.6 ± 16.9 years old. The under-40 group involved 42 eyes from 42 patients, and the over-40 group included 102 eyes from 102 patients. Symptom duration was shorter in the under-40 group compared to the over-40 group (7.6 ± 10.7 days vs. 14.5 ± 24.4 days; p = 0.029). Proliferative vitreoretinopathy (PVR) occurred more frequently in the under-40 group (40.0% vs. 17.4%, p = 0.007) than in the over-40 group. The anatomical success rate of primary surgery was significantly different between the two groups; 78.6% in the under-40 group and 91.2% in the over-40 group (p = 0.038). Preoperative PVR increased the rate of anatomical failure (40.0% vs. 6.2%, p < 0.001). The visual outcomes were not significantly different between the two groups. CONCLUSIONS: RRD is combined with PVR more frequently in young patients than in old patients, which increases the failure rate of primary re-attachment surgery.

Comparison of Central Corneal Thickness and Anterior Chamber Depth Measured Using Three Different Devices

PURPOSE: To compare measurements of central corneal thickness (CCT) and anterior chamber depth (ACD) obtained using Galilei(TM), Pentacam(R) (Oculus, Wetzlar, Germany) and Lenstar(R) (Haag-Streit, Koeniz, Switzerland) and analyze the measurement agreements. METHODS: CCT and ACD were measured using Galilei(TM), Pentacam(R) and Lenstar(R) in 47 eyes of 25 healthy subjects. The measurements were compared among the 3 devices. RESULTS: The average CCT measurements using Galilei(TM), Pentacam(R) and Lenstar(R) were 552.6 +/- 29.41 microm, 543.9 +/- 30.50 microm and 537.5 +/- 30.26 microm, respectively. The measurements significantly correlated with each other (r > 0.9, p 0.9, p < 0.001), but were statistically significantly different (p = 0.034). The CCT 95% limits of agreement (LoA) between Galilei(TM) and Pentacam(R), Pentacam(R) and Lenstar(R) and Lenstar(R) and Galilei(TM) were 31.95 microm, 44.76 microm and 46.57 microm, respectively and 95% ACD LoA were 0.46 mm, 0.32 mm and 0.28 mm, respectively. CONCLUSIONS: CCT and ACD measured using the 3 devices were highly correlated with each other but the measurements were statistically different. Therefore, the measurements were not interchangeable and these differences should be considered in clinical use.

Inadvertent Intralenticular Dexamethasone Implant for Diabetic Macular Edema Unresponsive to Bevacizumab

PURPOSE: To report a case of inadvertent intralenticular slow-release dexamthasone implant (Ozurdex(R), Allergan Inc., Irvine, CA, USA) for diabetic macular edema unresponsive to bevacizumab. CASE SUMMARY: A 71-year-old woman presented with proliferative diabetic retinopathy. During follow-up, diabetic macular edema developed in both eyes and did not improve with intravitreal bevacizumab injections. For refractory diabetic macular edema, slow-release dexamthasone implant (Ozurdex(R)) was to be injected at the vitreous cavity of her left eye, but it was inadvertently injected into the crystalline lens. The patient was followed closely for 10 months. Diabetic macular edema completely resolved 1 month after the injection and did not recur during follow-up. There were no severe complications except mild cataract formation. Best-corrected visual acuity for the left eye improved from 0.1 to 0.2. The Ozurdex(R) implant slightly decreased after 10 months, but was still observed in the crystalline lens. CONCLUSIONS: The inadvertent intralenticular dexamthasone implant was a rare complication but effective for diabetic macular edema.

A Case of Vitreous Prolapse through Iridectomy Site after Trabeculectomy

PURPOSE: To report the results of anterior vitrectomy for obstruction of the aqueous outflow shunt by prolapsed vitreous strands after trabeculectomy. CASE SUMMARY: Trabeculectomy was performed on a pseudophakic primary open angle glaucoma patient with uncontrolled intraocular pressure under maximum tolerable medical therapy. Three months after trabeculectomy, the bleb flattened and the intraocular pressure elevated. On gonioscopic examination, vitreous strands prolapsed through the iridectomy site obstructing the inner ostium. The maximum tolerable medical therapy and Nd:YAG laser vitreolysis were attempted, but the intraocular pressure was not controlled. Anterior vitrectomy was performed to remove the prolapsed vitreous strands. After anterior vitrectomy, the bleb regained filtering function and the intraocular pressure was stabilized. CONCLUSIONS: In a case with a prolapsed vitreous into the anterior chamber obstructing the outflow shunt of the aqueous humor after trabeculectomy, anterior vitrectomy showed therapeutic effects.

A Case of Vitreous Prolapse through Iridectomy Site after Trabeculectomy

PURPOSE: To report the results of anterior vitrectomy for obstruction of the aqueous outflow shunt by prolapsed vitreous strands after trabeculectomy. CASE SUMMARY: Trabeculectomy was performed on a pseudophakic primary open angle glaucoma patient with uncontrolled intraocular pressure under maximum tolerable medical therapy. Three months after trabeculectomy, the bleb flattened and the intraocular pressure elevated. On gonioscopic examination, vitreous strands prolapsed through the iridectomy site obstructing the inner ostium. The maximum tolerable medical therapy and Nd:YAG laser vitreolysis were attempted, but the intraocular pressure was not controlled. Anterior vitrectomy was performed to remove the prolapsed vitreous strands. After anterior vitrectomy, the bleb regained filtering function and the intraocular pressure was stabilized. CONCLUSIONS: In a case with a prolapsed vitreous into the anterior chamber obstructing the outflow shunt of the aqueous humor after trabeculectomy, anterior vitrectomy showed therapeutic effects.

Pegylated Interferon-Associated Severe Retinopathy in a Patient with Chronic Hepatitis

This paper reports a case of pegylated interferon-associated retinopathy in a patient with chronic hepatitis C. A 32-year-old female with chronic hepatitis C undergoing pegylated interferon and ribavirin combination therapy complained of visual blurring. Features of interferon-associated retinopathy, including ocular complications such as cotton wool spots, retinal hemorrhages, macular edema, and branch retinal vein occlusion, were found in the fundus of both of her eyes. Pegylated interferon combination therapy was stopped, and the retinopathy of the patient was treated with intravitreal bevacizumab injections and panretinal photocoagulations. This case shows that pharmacokinetically improved pegylated interferon has ocular complications for patients with chronic hepatitis C. Accordingly, patients undergoing pegylated interferon treatment for hepatitis C need regular eye examinations for protection of their vision.

The Treatment of Epithelial Ingrowth After Phacoemlusification Through Clear Cornea Incision

PURPOSE: To report a case of epithelial ingrowth treatment by surgical excision of epithelial tissues and intracameral 5-fluorouracil injection. CASE SUMMARY: A 70-year-old female patient who underwent phacoemulsification through clear cornea incision in both eyes 2 years before, was referred for her left ocular pain and corneal edema of 3 months' duration. Diffuse sheet-like epithelium grew from the clear cornea incision site to the pupil margin lesion of the iris. The epithelial tissues were excised and 5-fluorouracil was injected intracamerally. There were no recurrences for 2 months.

Pegylated Interferon Associated Retinopathy in Chronic Hepatitis Patients

PURPOSE: To investigate clinical features of pegylated interferon-associated retinopathy in chronic hepatitis patients. METHODS: The present study was a consecutive case series of 46 patients who were treated with pegylated interferon for chronic hepatitis C or B from October 2007 to September 2008 in our hospital. The patients had a regular ophthalmologic examination every 3 weeks for 6 months after treatment. RESULTS: Out of 46 patients, 10 patients (21.73%) developed retinal abnormality. Pegylated interferon-associated retinopathy occurred at 7.25+/-10.28 weeks after the treatment with cotton-wool spots and retinal hemorrhage. All cases except one mild nonproliferative diabetic retinopathy case presenting broad perimacular non-perfusion recovered without cessation of the treatment. CONCLUSIONS: Pegylated interferon-associated retinopathy in chronic hepatitis patients was reversible and had a recovery without visual complication. However, a single case did present with irreversible visual impairment. Pegylated interferon-associated retinopathy is usually asymptomatic and clinicians should observe patients closely for 3 months after treatment.

The Predictive Factors of the Serum Creatine Kinase Level Normalization Time in Patients with Rhabdomyolysis due to Doxylamine Ingestion

PURPOSE: Doxylamine succinate (DS) is frequently used to treat insomnia and it may induce rhabdomyolysis in the overdose cases. The purpose of this study is to evaluate the factors that can predict the serum creatine kinase (CK) level normalization time for patients with rhabdomyolysis due to DS ingestion. METHODS: This study was conducted on 71 patients who were admitted with rhabdomyolysis after DS ingestion during the period from January 2000 to July 2009. Rhabdomyolysis was defined as a serum CK level over 1,000 U/L. The collected data included the general characteristics, the anticholinergic symptoms, the ingested dose, the peak serum CK level, the time interval (TI) from the event to the peak CK level and the TI from the event to a CK level below 1,000 U/L. We evaluated the correlation between the patients'variables and the TI from the event to the peak CK level time and the time for a CK level below 1,000 U/L. RESULTS: The mean ingested dose per body weight (BW) was 30.86+/-18.63 mg/kg and the mean TI from the event to treatment was 4.04+/-3.67 hours. The TI from the event to the peak CK level was longer for the patients with a larger ingestion dose per BW (r=0.587, p<0.05). The CK normalization time was longer for the patients with a larger ingested dose per BW (r=0.446, p<0.05) and a higher peak CK level (r=0.634, p<0.05). CONCLUSION: The ingested dose per BW was correlated with the TI from the event to the peak CK level, and the ingested dose per BW and the peak CK level have significant correlations with the CK normalization time. These factors may be used to determine the discharge period of patients who had rhabdomyolysis following a DS overdose.

Modulation of Amygdalin on Glycine- and Glutamate-induced Ion Currents in Rat Periaqueductal Gray Neurons

Amygdalin is known as vitamain B17, and it was called laetrile. Amygdalin is composed of two molecules of glucose, one molecule of benzaldehyde which induces an analgesic action, and one molecule of hydrocyanic acid which is an anti-neoplastic compound. Amygdalin had been used to treat cancers and relieve pain. In order to evaluate whether the analgesic action of amygdalin is related with descending pain control system, we performed patch clamp study. In the present study, the modulatory effects of amygdalin on glycine- and glutamate-induced ion currents in periaqueductal gray (PAG) neurons were investigated using the nystatin-perforated patch clamp method. Continuous application of lipopolysaccharides (LPS) on PAG neurons resulted in increased glycine-induced ion current, and in decreased glutamate-induced ion current. In contrast, continuous application of amygdalin with LPS resulted in decreased glycine-induced ion current increased by LPS, and increased glutamate- induced ion current decreased by LPS in concentration- and time-dependent fashion. These results demonstrate that amygdalin modulates neuronal activity of PAG by modulation of glycine and glutamate. Based on the present results, it can be suggested that amygdalin participates in the regulation of the descending pain control system in the level of PAG neurons. The present study demonstrated that activation of the descending pain control system is one of the possible analgesic mechanisms of amygdalin.

The Abnormalities of Retinal Arteriole in Atherothrombotic Ischemic Stroke Patients Representing the Changes of Cerebral Vasculature Indirectly

PURPOSE: Retinal blood vessels and cerebral small vessels possess similar characteristics anatomically, physiologically and embryologically. We studied the availability of abnormal fundus findings of patients who had an atherothrombotic ischemic stroke and who have the risk factors. METHODS: Fundus photographs and brain images were taken in patients who had a first-ever symptomatic ischemic stroke of large artery atherosclerosis (LAA) or small vessel occlusion (SVO) from March 2004 to February 2005. We analyzed the association between fundus abnormalities and ischemic stroke subtypes. RESULTS: Based on brain MRI and MRA, a total of 47 patients were classified into SVO and LAA groups. The SVO group consisted of 27 patients (mean age: 69.7 years), and the LAA group consisted of 20 patients (mean age: 65.4 years). The control group comprised 15 patients (mean age: 64.9 years). The baseline characteristics were similar among the three groups. The severity of the retinal arteriolar narrowing and sclerosis were associated with hypertension. Compared to the control group, both the SVO and LAA groups showed more severe arteriolar sclerosis, the SVO group showed more severe arteriolar narrowing and the LAA group showed more frequent AV crossing and retinal exudate. CONCLUSIONS: Retinal arteriolar abnormalities such as arteriolar narrowing and sclerosis are more severe in atherothrombotic ischemic stroke patients. Indirectly, retinal microvascular changes may indicate the status of the cerebral vasculature. Thus, analysis of fundus findings is useful for predicting an atherothrombotic ischemic stroke and planning follow-up examinations.

Acute Effect of Alcohol and Nicotine on 5-Hydroxytryptamine Synthesis and Tryptophan Hydroxylase Expression in Dorsal and Median Raphe of Rats

Alcohol abuse and cigarette smoking have been on the rise worldwide and it has been reported that alcohol and nicotine influence serotonergic neuronal activity in the dorsal raphe. Serotonin (5-hydroxytryptamine, 5-HT) has been implicated in the pathophysiology of various neuropsychiatric disorders. In the present study, the effects of alcohol and nicotine on the synthesis of 5-HT and the expression of tryptophan hydroxylase (TPH), the rate limiting enzyme of 5-HT synthesis, in the dorsal and median raphe of young rats were investigated via immunohistochemistry. The numbers of the 5-HT-positive and TPH-positive cells in raphe nuclei were reduced by alcohol and nicotine treatment, and these numbers were reduced more potently by co-administration of alcohol and nicotine. Based on the results, it can be suggested that the pathogenesis of alcohol- and nicotine-induced neuropsychological disorders involves alcohol- and nicotine-induced suppression of 5-HT synthesis and TPH expression in raphe, and that this may be of particular relevance in the consumption of alcohol and nicotine during adolescence.

Caffeine Induces Apoptosis in Human Neuroblastoma Cell Line SK-N-MC

Caffeine is one of the most widely consumed neuroactive drugs, coming mostly from everyday beverages such as coffee and tea. To investigate whether caffeine induces apoptosis in the central nervous system, 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, flow cytometric analysis, DNA fragmentation assay, and caspase-3 enzyme assay were performed on SK-N-MC human neuroblastoma cells. Cells treated with caffeine at concentrations as high as 10 mM exhibited several characteristics of apoptosis. In addition, caffeine was shown to increase the caspase-3 activity. These results suggest that high-dose of caffeine induces apoptosis in human neuroblastoma cells, probably by increasing the caspase-3 enzyme activity.