Atropine Treatment Research Articles

Objective evaluation of the systemic effects of topical application of 1% atropine sulfate ophthalmic solution in healthy horses.

OBJECTIVE To determine the safety of topical administration of 1% atropine ophthalmic solution in healthy horses by objectively measuring gastrointestinal transit time. DESIGN Randomized, masked, controlled crossover study. ANIMALS 6 adult geldings. PROCEDURES Horses were randomly assigned (3/group) to first receive topical treatment of the left eye with 1% atropine or artificial tears solution; the right eye was left untreated. After 24 hours of treatment every 6 hours, 200 nontoxic beads were administered to each horse via nasogastric intubation and treatment frequency was decreased to every 12 hours for 4 more days. Pupillary light reflexes (PLRs), mydriasis, heart rate, fecal bead passage, abdominal girth measurements, auscultable gut sounds, fecal weight, and clinical signs of abdominal pain were monitored. Following a 4-week washout period, horses received the opposite treatment in the left eye and measurements were repeated. Serum atropine concentration (reflecting systemic absorption) was measured with an ELISA at various points after initial atropine administration. RESULTS No horse had subjective or objective evidence of colic or ileus at any monitoring point. Complete mydriasis of the left eye with absence of the PLR was identified in 5 horses within 6 hours and in all 6 horses within 12 hours after initial atropine administration. One horse had mydriasis with an absent PLR in the untreated eye by day 5 of atropine treatment. At no point was atropine detected in serum samples of any horse. CONCLUSIONS AND CLINICAL RELEVANCE Topical atropine application at clinically appropriate doses induced no evidence of ileus in healthy horses.

Optic Disc Parameters of Myopic Children with Atropine Treatment

ABSTRACTPurpose: To characterize optic disc parameters, retinal nerve fiber layer thickness (RNFLT), and the intraocular pressure (IOP) of myopic children under continual topical 0.25% atropine treatment.Methods: From October 1, 2010 to September 31, 2011, 67 eyes of 35 myopic children were recruited. The children were treated with 0.25% atropine nightly for myopia control. Visual acuity, refraction, IOP, axial length (AL, IOL Master), RNFLT, and optic disc parameters (Stratus OCT) were measured at enrollment and every 2 months. All patients had at least 1 year of follow-up.Results: Enrolled children had a mean age of 10.3 ± 2.4 years (5–15 years). Of the 67 studied eyes, the mean spherical equivalent (SE) was −2.60 ± 1.58 diopters (D) (−6.75–−0.5 D). Under the treatment of 0.25% atropine, myopia increased by 0.53 ± 0.10D per year (P < 0.0001), and AL elongated by 0.245 ± 0.042 mm per year (P < 0.0001). No significant change was noted in the IOP and optic nerve parameters including peripapillary RNFLT, areas of optic disc, cup and rim, or cup/disc ratio over the follow-up period during atropine treatment (P > 0.05).Conclusions: 0.25% Atropine treatment for myopia control did not significantly affect the IOP, optic nerve parameters, and RNFLT in children over a mean of 15.2 ± 2.4 months treatment and follow-up. 0.25% Atropine is a relatively safe option for myopia control.

Neuroprotective Effects of Galantamine on Nerve Agent-Induced Neuroglial and Biochemical Changes.

Neuroprotection from nerve agent such as soman-induced neural damage is a major challenge for existing drugs. Nerve agent exposure can cause many neural effects in survivors arising mainly due to acetylcholinesterase (AChE) inhibition or death within minutes. Unraveling the mechanisms underlying the nerve agent-induced multiple neurological effects is useful to develop better and safe drugs. The present study aimed to understand the molecular response during soman exposure and to evaluate the neuroprotective efficacy of galantamine on nerve agent-induced neurotoxic changes. mRNA expression studies using quantitative real-time PCR revealed significant changes in S-100β, Gfap, c-fos, and Bdnf in the hippocampus and piriform cortex after soman (90μg/kg, s.c) exposure. Immunoblot analysis showed acute soman exposure significantly increased the protein levels of neuroglial markers (S100-β and GFAP); c-Fos and protein oxidation in discrete rat brain areas indicate their role in nerve agent-induced neurotoxicity. Induction of BDNF levels during soman exposure may indicate the recovery mechanisms activation. AChE was inhibited in the blood and brain up to 82% after soman exposure. Antidotal treatment with galantamine alone (3mg/kg) and galantamine plus atropine (10mg/kg) has protected animals from nerve agent-induced intoxication, death, and soman-inhibited AChE up to 45% in the blood and brain. Animal received galantamine displayed increased levels of neuroprotective genes (nAChRα-7, Bcl-2, and Bdnf) in the brain suggest the neuroprotective value of galantamine. Neuroglial changes, c-Fos, and protein oxidation levels significantly reduced after galantamine and galantamine plus atropine treatment indicate their potential antidotal value in nerve agent treatment.

Semptomdan Tanıya Organofosfat İntoksikasyonu

Poisoning is an important health problem that is common in emergency services. Delay in intervention in the acute process of poisoning can lead to increased mortality and morbidity. Organic phosphorus compounds are widely used in agriculture, in houses, in gardens, in veterinary medicine and in chemical weapons production all around the world. Approximately 3 million people are exposed to organophosphates per year and nearly 300 thousand die. We present a 13-year-old previously healthy girl with generalized tonic clonic seizures. Although there was no pertinent poisoning history, the diagnosis was made based on the clinical signs and the dramatic response to atropine and pralidoxime treatments. After the resolution of the symptoms, the patient confessed that she had attempted suicide with an insecticide. Emergency organophosphate intoxication should be considered especially if abdominal cramps, increased lacrimation and salivation, respiratory distress, arrhythmia, anxiety, seizure, and decreased consciousness are observed in previously healthy children.

Antioxidant and Osmoprotecting Activity of Taurine in Dry Eye Models.

To assess the protective effects of ophthalmic formulations based on taurine (TAU) and sodium hyaluronate (SH) in ocular surface. Rabbit corneal epithelial cells [Statens Seruminstitut Rabbit Cornea (SIRC)] were subjected to oxidative stress (1 mM H2O2) and treated with the following formulations: 0.2% SH, 0.4% SH, 0.4% SH +0.5% TAU. Reactive oxygen species (ROS) were evaluated by commercial kit. Dry eye was induced by atropine sulfate and topical treatment was carried out with the following formulations: 0.2% SH, 0.4% SH, 0.4% SH +0.5% TAU. Schirmer's test, tear breakup time (TBUT), and tear osmolarity were evaluated. Furthermore, tear matrix metalloproteinase 9 (MMP-9) expression was assessed by Western blot. TAU significantly (P < 0.05) decreased ROS production in SIRC after oxidative stress. Topical administration of atropine in the rabbit eye significantly (P < 0.05) reduced tear volume and TBUT. Tear osmolarity was also significantly (P < 0.05) modified by atropine treatment. All the altered parameters were significantly (P < 0.05) reversed by 0.5% TAU +0.4% SH treatment; furthermore, this formulation was more effective than SH alone. Moreover, tear levels of MMP-9 were significantly (P < 0.05) lower in the group treated with 0.5% TAU +0.4% SH. Altogether these data suggest that TAU has a relevant antioxidant effect in corneal epithelial cells and prevents the ocular surface damage elicited by atropine. Therefore, our findings suggest that TAU in combination with SH may be useful in clinical practice to manage ocular surface diseases.

Acetylcholine contributes to the integration of self-movement cues in head direction cells.

Acetylcholine contributes to accurate performance on some navigational tasks, but details of its contribution to the underlying brain signals are not fully understood. The medial septal area provides widespread cholinergic input to various brain regions, but selective damage to medial septal cholinergic neurons generally has little effect on landmark-based navigation, or the underlying neural representations of location and directional heading in visual environments. In contrast, the loss of medial septal cholinergic neurons disrupts navigation based on path integration, but no studies have tested whether these path integration deficits are associated with disrupted head direction (HD) cell activity. Therefore, we evaluated HD cell responses to visual cue rotations in a familiar arena, and during navigation between familiar and novel arenas, after muscarinic receptor blockade with systemic atropine. Atropine treatment reduced the peak firing rate of HD cells, but failed to significantly affect other HD cell firing properties. Atropine also failed to significantly disrupt the dominant landmark control of the HD signal, even though we used a procedure that challenged this landmark control. In contrast, atropine disrupted HD cell stability during navigation between familiar and novel arenas, where path integration normally maintains a consistent HD cell signal across arenas. These results suggest that acetylcholine contributes to path integration, in part, by facilitating the use of idiothetic cues to maintain a consistent representation of directional heading. (PsycINFO Database Record

Increased risk for hypothyroidism after anticholinesterase pesticide poisoning: a nationwide population-based study

Previous animal studies have reported that acute anticholinesterase pesticide (organophosphate and carbamate) poisoning may affect thyroid hormones. However, there is no human study investigating the association between hypothyroidism and anticholinesterase pesticide poisoning, and therefore, we conducted a retrospective nationwide population-based cohort study to delineate this issue. We identified 10,372 anticholinesterase pesticide poisoning subjects and matched 31,116 non-anticholinesterase pesticide poisoning subjects between 2003 and 2012 from the Nationwide Poisoning Database and the Longitudinal Health Insurance Database 2000, respectively, in a 1:3 ratio by index date, age, and sex for this study. We compared the cumulative incidence of hypothyroidism between the two cohorts by following up until 2013. Independent predictors for hypothyroidism were also investigated. In total, 75 (0.72%) anticholinesterase pesticide poisoning subjects and 184 (0.59%) non-anticholinesterase pesticide poisoning subjects were diagnosed with hypothyroidism during the follow-up. Cox proportional hazard regression analysis showed that anticholinesterase pesticide poisoning subjects had higher risk for hypothyroidism than did non-anticholinesterase pesticide poisoning subjects (adjusted hazard ratio: 1.47, 95% confidence interval: 1.11-1.95) after adjusting for age, sex, hypertension, malignancy, liver disease, renal disease, atrial fibrillation or flutter, thyroiditis, goiter, other endocrine disorders, and mental disorder. Stratified analysis showed that anticholinesterase pesticide poisoning subjects had higher risk for hypothyroidism than did non-anticholinesterase pesticide poisoning subjects in terms of the age subgroup of 40-64 years, female sex, past history of goiter, follow-up of <1 month, and anticholinesterase pesticide poisoning subjects without atropine treatment (incidence rate ratio [IRR]: 1.66, 95% confidence interval: 1.20-2.30). Female sex, malignancy, renal disease, thyroiditis, goiter, mental disorder, and anticholinesterase pesticide poisoning without atropine treatment were independent predictors for hypothyroidism. Anticholinesterase pesticide poisoning is associated with increased risk for hypothyroidism. Early evaluation of thyroid function in anticholinesterase pesticide poisoning subjects is suggested, especially in subjects without atropine treatment, aged 40-64 years, female sex, and past history of goiter.

Optimization of the Ocular Treatment Following Organophosphate Nerve Agent Insult.

Eye exposure to organophosphate (OP) irreversible acetylcholinesterase inhibitors, results in long-term miosis and impaired visual function. The aim of this study was to find an anticholinergic antidote, which would counteract miosis and visual impairment induced by the nerve agents sarin and VX with minimal untoward side-effects. Rat pupil width and light reflex were evaluated from 15 min up to 2 weeks following topical OP exposure with or without topical ocular treatment of atropine or homatropine or with a combined intramuscular treatment of trimedoxime (TMB-4) and atropine (TA). Visual function following insult and treatment was assessed using a cued Morris water maze task. Topical VX exposure showed a dose-dependent miosis with a significant reduction in visual function similar to the effect seen following sarin exposure. Homatropine (2%; w/v) and atropine (0.1%; w/v) treatment ameliorated both sarin and VX-induced miosis and the resulting visual impairment. TA treatment was sufficient in ameliorating the sarin-induced ocular impairment while an additional ocular treatment with either 0.1% atropine or 2% homatropine was necessary following VX exposure. To conclude the use of 0.1% atropine or 2% homatropine was beneficial in ameliorating the ocular insult following VX or sarin ocular exposure and thus should be considered as universal treatments against this intoxication. The findings also emphasize the necessity of additional ocular treatment to the systemic treatment in visually impaired casualties following VX exposure.

The immune-regulating effect of Xiao\u2019er Qixingcha in constipated mice induced by high-heat and high-protein diet

BackgroundXiao’er Qixingcha (EXQ) has been extensively applied to relieve dyspepsia and constipation in children for hundreds of years in China. However, the therapeutic mechanism underlying its efficacy remained to be defined. The present study aimed to clarify the possible laxative and immune-regulating effects of EXQ on two models of experimental constipation in mice, which mimicked the pediatric constipation caused by high-heat and high-protein diet (HHPD).MethodsThe two models of constipated mice were induced by HHPD or HHPD + atropine respectively. To investigate the laxative and immune-regulating activities of EXQ, animals were treated with three doses of EXQ (0.75, 1.5 and 3 g/kg) for 7 consecutive days. The fecal output parameters (number and weight), weight of intestinal content and, the thymus and spleen indexes were measured. The levels of sIgA, IL-10, TNF-α and LPS in colon and serum were determined by ELISA. Furthermore, the pathological changes of colon tissue were examined after routine H&E staining.ResultsBoth HHPD and HHPD + atropine treatments obviously inhibited the fecal output and reduced the colonic sIgA, prominently increased the levels of IL-10 and TNF-α in colonic tissue and elevated the contents of LPS in serum and colonic tissues. In contrast, oral administration of EXQ significantly improved the feces characters and dose-dependently decreased the intestinal changes in both models. In HHPD model test, EXQ efficaciously boosted the sIgA level in a dose-dependent manner, significantly elicited decreases in TNF-α and IL-10 levels, and evidently decreased the spleen and thymus indexes. In HHPD + atropine model test, EXQ treatment reversed the pathological changes by not only dramatically decreasing the spleen index and the levels of LPS and IL-10, but also markedly elevating the thymus index. Furthermore, microscopic observation revealed that EXQ treatment maintained the integrity of colonic mucosa, and protected the colonic tissues from inflammation in the both models.ConclusionsEXQ exhibited prominent laxative activity and effectively protected the colonic mucosal barrier in two models of constipated mice, of which the mechanism might be closely associated with its propulsive and immune-regulating properties. The current results not only validated the rationale for the clinical application of EXQ in pediatric constipation related symptoms, but also threw new light on the immune-inflammatory responses accompanied with chronic constipation pathology.

Intraocular pressure monitoring by rebound tonometry in children with myopia.

BACKGROUND/PURPOSE:Topical atropine treatment is generally accepted to retard the progression of myopia, but it is associated with side effects such as photophobia and elevation of intraocular pressure (IOP). IOP measurements in children are challenging. The traditional applanation tonometry by direct contact with the cornea will require patient's cooperation. The rebound tonometer, using a dynamic electromechanical method for measuring IOP, shows good correlation with traditional tonometry. The purpose of this study is to evaluate the IOP of myopic children under atropine treatment using rebound tonometer and to compare the characteristics between rebound tonometry and applanation tonometry.METHODS:This study is a prospective study measuring IOP by rebound tonometer in myopic children under regular low-dose atropine treatment. We recruited children with refraction error showing myopia over −0.5 D with 0.15%, 0.3%, or 0.5% atropine eye drops use every night or every other night for myopia control. Children with treatment duration of atropine <1 month were excluded from the study. IOP measurements were performed by applanation tonometer (Tono-Pen XL, Reichert) and rebound tonometer (ICARE). The reliability of rebound tonometer was analyzed with percentage. Comparison of IOP between rebound tonometer and applanation tonometry was presented.RESULTS:The rebound tonometry was well tolerated by all participants and caused no complaints, discomfort, or adverse events. Totally 42 myopic eyes of 42 subjects were included in the study. The average age of these participants was 10 years old, range from 5 to 16. Median = 10 years old. The average IOP of the right eye by rebound tonometer was 17.4 ± 3 mmHg, and 17.1 ± 3 mmHg by applanation tonometry. Nearly 19%, 33%, and 24% of difference of IOP readings between rebound tonometer and Tono-Pen applanation are within 0 mmHg, 1 mmHg, and 1–2 mmHg, respectively.CONCLUSIONS:Rebound tonometry has good correlation with applanation tonometry and 76.1% of differences between two tonometers are <2 mmHg. The advantage of drop-free rebound tonometry has made it easier to obtain IOP readings in myopia children under atropine treatment.

Biochemical and histopathological changes in the brain of albino rats treated with profenofos and the possible protective effect of vitamins C and E

Objective The aim of this study was to evaluate the changes in the brain of albino rats treated with profenofos and the possible protective effect of vitamins C and E against the acute effect of profenofos. Background During the last decades the use of pesticides has increased steadily in developing countries in an effort to increase food production and control vector-borne diseases in plants. Organophosphorus (OP) compounds are widely used in agriculture as insecticides. OP poisoning is common due to its wide availability. Profenofos is a widely used insecticide and has been classified as moderately hazardous. OP pesticides are known to inhibit cholinesterase activity in target tissues. Oxidative stress is one of the possible mechanisms that could be involved in OP toxicity. Patients and methods Eighty adult male albino rats were divided randomly into four main groups: the control group (I), the profenofos toxicity group (group II), the profenofos + antidote-treated group (group III), and the profenofos + antidote + antioxidant-treated group (group IV). Each treated group was divided equally into two subgroups. Ten rats from each subgroup were killed after 24 h to demonstrate the toxicity. The other 10 rats were killed after 7 days to demonstrate the recovery. Brain samples were obtained for biochemical, histopathological, and immunohistochemical studies. Results Acute exposure to profenofos causes biochemical and histopathological changes in brain tissue. These changes were minimized with atropine and oxime treatment. However, this recovery was more prominent in the group administered vitamins C and E. Conclusion Treatment with vitamins C and E exerts an antioxidative effect and this may be responsible for the amelioration of profenofos-provoked toxicity.

Pain Measurement in Mechanically Ventilated Patients with Traumatic Brain Injury: Behavioral Pain Tools Versus Analgesia Nociception Index.

Introduction:Pain is highly prevalent in critically ill trauma patients, especially those with a traumatic brain injury (TBI). Behavioral pain tools such as the behavioral pain scale (BPS) and critical-care pain observation tool are recommended for sedated noncommunicative patients. Analysis of heart rate variability (HRV) is a noninvasive method to evaluate autonomic nervous system activity. The analgesia nociception index (ANI) device (Physiodoloris®, MDoloris Medical Systems, Loos, France) allows noninvasive HRV analysis. The ANI assesses the relative parasympathetic tone as a surrogate for antinociception/nociception balance in sedated patients. The primary aim of our study was to evaluate the effectiveness of ANI in detecting pain in TBI patients. The secondary aim was to evaluate the impact of norepinephrine use on ANI effectiveness and to determine the correlation between ANI and BPS.Methods:We performed a prospective observational study in 21 deeply sedated TBI patients. Exclusion criteria were nonsinus cardiac rhythm; presence of pacemaker; atropine or isoprenaline treatment; neuromuscular blocking agents; and major cognitive impairment. Heart rate, blood pressure, and ANI were continuously recorded using the Physiodoloris® device at rest (T1), during (T2), and after the end (T3) of the painful stimulus (tracheal suctioning).Results:In total, 100 observations were scored. ANI was significantly lower at T2 (Median [min – max] 54.5 [22–100]) compared with T1 (90.5 [50–100], P < 0.0001) and T3 (82 [36–100], P < 0.0001). Similar results were found in the subgroups of patients with (65 measurements) or without (35) norepinephrine. During procedure, a negative linear relationship was observed between ANI and BPS (r2 = −0.469, P < 0.001). At the threshold of 50, the sensitivity and specificity of ANI to detect patients with BPS ≥ 5 were 73% and 62%, respectively, with a negative predictive value of 86%.Discussion:Our results suggest that ANI is effective in detecting pain in ventilated sedated TBI patients, including those patients treated with norepinephrine.

Cellular Energetical Actions of "Chemical" and "Surgical" Vagotomy in Gastrointestinal Mucosal Damage and Protection: Similarities, Differences and Significance for Brain-Gut Function.

BackgroundThe authors, as internists, registered significant difference in the long lasting actions of surgical and chemical (atropine treatment) vagotomy in patients with peptic ulcer during second half of the last century (efficency, gastric acid secretion, gastrointestinal side effects, briefly benefical and harmful actions were examined).Aims1. Since the authors participated in the establishing of human clinical pharmacology in this field, they wanted to know more and more facts of the acute and chronic effects of surgical and chemical (atropine treatment) on the gastrointestinal mucosal biochemisms and their actions altered by bioactive compounds and scavengers regarding the development of gastric mucosal damage and protection.MethodsThe observations were carried out in animals under various experimental conditions (in intact, pylorus-ligated rats, in different experimental ulcer models, together with application of various mucosal protecting compounds) without and with surgical vagotomy and chemical vagotomy produced by atropine treatment.Results1. No changes were obtained in the cellular energy systems (ATP, ADP, AMP, cAMP, “adenylate pool”, “energy charge“ [(ATP+ 0.5 ADP)/ (ATP+ADP+AMP)] of stomach (glandular part, forestomach) in pylorus ligated rats after surgical vagotomy in contrast to those produced by only chemical vagotomy; 2. The effects of the gastric mucosal protective compounds [atropine, cimetidine, prostaglandins, scavengers (like vitamin A, β-carotene), capsaicin] disappeared after surgical vagotomy; 3. The extents of different chemical agents induced mucosal damaging effects were enhanced by surgical vagotomy and was not altered by chemical vagotomy; 4. The existence of feedback mechanisms of pharmacological (cellular and intracellular) regulatory mechanisms between the membrane-bound ATP-dependent energy systems exists in the gastric mucosa of intact animals, and after chemical vagotomy, but not after surgical vagotomy.Conclusions1. Increased vagal nerve activity takes place in the gastric mucosal damage; 2 both surgical and chemical vagotomy result mucosal protective affect on the gastric mucosal in different damaging experimental models; 3. The capsaicin-induced gastric mucosal damage depends on the applied doses, presence of anatomically intact vagal nerve (but independent from the chemical vagotomy), 4. The central and pheripheral neural regulations differ during gastric mucosal damage and protection induced by drugs, bioactive compounds, scavengers.

Alterations in ACE and ABCG2 expression levels in the testes of rats subjected to atropine-induced toxicity.

Atropine-induced damage is associated with enzyme and protein alterations. The aim of the present study was to investigate atropine‑induced alterations in testicular expression levels of angiotensin‑converting enzyme (ACE) and adenosine 5'-triphosphate binding cassette sub‑family G member 2 (ABCG2) following atropine treatment. Male Wistar rats received 15mg/kg/day atropine for 7days; control rats received an identical volume of saline, Following treatment, the testes were harvested for immunohistochemistry and insitu hybridization to examine the protein and gene expression levels of ACE and ABCG2 by digital image analysis. ACE gene and protein expression levels were significantly reduced in the testes of atropine‑treated rats, compared with control rats (P=0.0001 and P<0.001, respectively). In addition, ABCG2 gene and protein expression levels were significantly increased in the testes of atropine‑treated rats, compared with control rats (P=0.0017 and P<0.001, respectively). Thus, the results of the present study demonstrate that testicular protein and gene expression levels of ACE and ABCG2 were altered as a result of atropine‑induced toxicity in the rats. These alterations may result in abnormal testicular function, and the proteins and genes identified in the present study may be useful to elucidate the mechanisms underlying atropine‑induced toxicity and provide a direction for further studies.

Methyl-CpG binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis.

Sudden unexpected death occurs in one quarter of deaths in Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). People with RTT show a variety of autonomic nervous system (ANS) abnormalities and mouse models show similar problems including QTc interval prolongation and hypothermia. To explore the role of cardiac problems in sudden death in RTT, we characterized cardiac rhythm in mice lacking Mecp2 function. Male and female mutant mice exhibited spontaneous cardiac rhythm abnormalities including bradycardic events, sinus pauses, atrioventricular block, premature ventricular contractions, non-sustained ventricular arrhythmias, and increased heart rate variability. Death was associated with spontaneous cardiac arrhythmias and complete conduction block. Atropine treatment reduced cardiac arrhythmias in mutant mice, implicating overactive parasympathetic tone. To explore the role of MeCP2 within the parasympathetic neurons, we selectively removed MeCP2 function from cholinergic neurons (MeCP2 ChAT KO), which recapitulated the cardiac rhythm abnormalities, hypothermia, and early death seen in RTT male mice. Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotypes. Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.

Taurine exerts antioxidant and osmoprotecting activity: an in vitro and in vivo study

PurposeTo evaluate the effects of ophthalmic solutions based on sodium hyaluronate (SH) with or without taurine (TAU) in experimental dry eye disease models.MethodsRabbit corneal epithelial cells (SIRCs) were exposed to oxidative stress (1 mM H2O2) and treated with the following formulations: 0.2% SH, 0.4% SH, 0.4% SH + 0.5% TAU. Reactive oxygen species (ROS) were assessed by commercial kit (ab113851). Dry eye was induced in albino rabbits by topical application (4 times per day) of 1% atropine eye drops. Fifteen minutes after atropine instillation we treated the eyes with test formulations (0.2% SH, 0.4% SH, 0.4% SH + 0.5% TAU). The following endpoints were evaluated: tear breakup time (TBUT), Schirmer's test, ferning test, tear osmolarity. Results were compared to negative (CTR‐; normal eye) and positive control groups (CTR+; atropine‐treated eye).ResultsTaurine significantly (p &lt; 0.01) quenched ROS production in SIRC after oxidative stress. The effect of taurine, in terms of ROS quenching, was significantly (p &lt; 0.01) higher compared to SH‐treated cells. Topical administration of atropine in the rabbit eye significantly (p &lt; 0.01) reduced tear volume and TBUT. Ferning test and tear osmolarity were also significantly (p &lt; 0.01) modified by atropine treatment. All the altered parameters were significantly (p &lt; 0.01) reversed by 0.4% SH + 0.5% TAU treatment. Furthermore, treatment with SH‐TAU formulation was more effective compared to SH formulations.ConclusionsAll together these data demonstrated that taurine has a potent antioxidant activity preventing the negative effect elicited by atropine on tear stability. Therefore, our findings support the hypothesis that the formulation containing taurine may be more useful than SH formulations in clinical practice to manage ocular surface diseases related to dry eye.

Anticholinergic premedication to prevent bradycardia in combined spinal anesthesia and dexmedetomidine sedation: a randomized, double-blind, placebo-controlled study

ObjectiveWhen dexmedetomidine is used in patients undergoing spinal anesthesia, high incidence of bradycardia in response to parasympathetic activation is reported. Therefore, we aimed to evaluate the effectiveness of atropine premedication for preventing the incidence of bradycardia and the hemodynamic effect on patients undergoing spinal anesthesia with sedation by dexmedetomidine. DesignRandomized, double-blind, placebo-controlled study. SettingOperating room. PatientsOne hundred fourteen patients (age range, 2-65 years; American Society of Anesthesiology class I-II) participated in this study, willing to be sedated and to undergo spinal anesthesia. InterventionThe patients were divided into 2 groups: group A and group C. After performing spinal anesthesia, dexmedetomidine was infused at a loading dose of 0.6 μg/kg for 10 minutes, followed by an infusion at 0.25 μg/(kg h). Simultaneously with the loading dose of dexmedetomidine, patients in group A received an intravenous bolus of 0.5 mg atropine, whereas patients in group C received an intravenous normal saline bolus. MeasurementData on administration of atropine and ephedrine were collected. Hemodynamic data including heart rate, systolic blood pressure, diastolic blood pressure (DBP), and mean blood pressure (MBP) were also recorded. Main resultsThe incidence of bradycardia requiring atropine treatment was significantly higher in group C than group A (P=.035). However, the incidence of hypotension needing ephedrine treatment showed no significant difference between the 2 groups (P=.7). Systolic blood pressure and heart rate showed no significant differences between the 2 groups (P=.138 and .464, respectively). However, group A showed significant increases in DBP and MBP, and group C did not (P=.014 and .008, respectively). ConclusionProphylactic atropine reduces the incidence of bradycardia in patients undergoing spinal anesthesia with dexmedetomidine sedation. However, DBP and MBP showed significant increases in patients when prophylactic atropine was administrated. Therefore, atropine premedication should be administered cautiously.

Abstract 1865: Areca nut-induced JNK/ATF2/Jun axis regulates TGF-beta signaling contributing to pre-cancerous oral submucous fibrosis

Abstract Oral Submucous Fibrosis (OSF) is an inflammatory, pre-cancerous condition of the oral submucosa. It affects individuals with prolonged areca nut chewing habit and therefore areca nut is regarded as the etiological agent for OSF manifestation. Transforming Growth Factor beta is an established promoter of cancer and fibrosis. Up-regulation of TGF-β and its target genes has also been reported in OSF. However, the underlying mechanism for the regulation of TGF-β by areca nut has not been elucidated. The present study demonstrates that TGF-β pathway is activated in epithelial cells after two hour exposure to areca nut extract. Areca nut increases TGF-β transcript as well as protein and thereby the downstream canonical Smad2/3 signaling. Pre-treatment with various pathway inhibitors showed JNK pathway activation as a pre-requisite to TGF-β pathway activation by areca nut. Areca nut activated JNK pathway within half an hour of treatment and this was reversed by atropine treatment suggesting involvement of muscarinic acid receptor signaling. Second messengers upstream to JNK activation and regulated by areca nut were calcium/CAMKII and reactive oxygen species. Further, areca nut treatment resulted in JNK dependent phosphorylation of ATF2 and c-Jun transcription factors. These were found to bind TGF-β promoter, as revealed by chromatin immunoprecipitation experiments. Expectedly, knockdown of these transcription factors abrogated areca nut induced TGF-β pathway activation. Based on the data obtained a model is proposed to elucidate activation of TGF-β pathway by areca nut extract involving activation of JNK and ATF2, c-Jun resulting in the over expression of TGF-β in epithelial cells which may contribute to the manifestation of OSF. Thus, this study highlights ATF2/c-Jun as the critical nodes for therapeutic intervention to prevent TGF-β over production in OSF. Funding by DST and CSIR is acknowledged. Citation Format: Ila Pant, Paturu Kondaiah. Areca nut-induced JNK/ATF2/Jun axis regulates TGF-beta signaling contributing to pre-cancerous oral submucous fibrosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1865.

Unilaterally blocking the muscarinic receptors in the suprachiasmatic nucleus in proestrus rats prevents pre-ovulatory LH secretion and ovulation.

BackgroundThe suprachiasmatic nucleus (SCN) and the cholinergic system of various regions of the hypothalamus participate in the regulation of gonadotropin-releasing hormone (GnRH) and gonadotropin secretion, which are necessary for the occurrence of ovulation. In the present study, our goal was to analyse the effects of unilaterally blocking the muscarinic receptors in the SCN on ovulation and steroid secretion.MethodsCyclic rats were randomly allotted to one of the experimental groups. Groups of 8–14 rats were anaesthetized and microinjected with 0.3 μl of saline or a solution of atropine (62.5 ng in 0.3 μl of saline) into the left or right SCN at 09.00 or 19.00 h during diestrus-1 or on the proestrus day. The rats were euthanized on the predicted day of oestrus, and evaluated ovulation and levels of progesterone and oestradiol. Other groups of 10 rats were microinjected with atropine into the left or right SCNs at 09.00 h on the proestrus day, were euthanized eight h later, and luteinizing hormone (LH) was measured.ResultsAt 09.00 or 19.00 h during diestrus-1, atropine microinjections into the SCNs on either side did not modify ovulation. The atropine microinjections performed at 09.00 h of proestrus into either side of the SCN blocked ovulation (right SCN: 1/9 ovulated vs. 9/10 in the saline group; left SCN: 8/14 ovulated vs. 10/10 in the saline group). The LH levels at 17.00 h in the rats that were microinjected with atropine at 09.00 h of proestrus were lower than those of the controls. In the non-ovulating atropine-treated rats, the injection of synthetic LH-releasing hormone (LHRH) restored ovulation. Atropine treatment at 19.00 h of proestrus on either side of the SCN did not modify ovulation, while the progesterone and oestradiol levels were lower.ConclusionBased on the present results, we suggest that the cholinergic neural information arriving on either side of the SCN is necessary for the pre-ovulatory secretion of LH to induce ovulation. Additionally, the regulation of progesterone and oestradiol secretion by the cholinergic innervation of the SCN varies with the time of day, the day of the cycle, and the affected SCN.

Effectiveness study of atropine for progressive myopia in Europeans.

PurposeRandomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country.MethodsAn effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy.ResultsMean spherical equivalent at baseline was −6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (−1.0D/year±0.7) diminished substantially during treatment (−0.1D/year±0.7) compared to those who ceased therapy (−0.5D/year±0.6; P=0.03).ConclusionsDespite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans.