This study reports the influence of miotics (pilocarpine) on the visual field by comparing two visual fields, one at the miotic state and the other at normal pupil size. The measurements from the Goldmann perimetry test of 10 ocular hypertensive eyes (7 patients) and 10 glaucomatous eyes (8 patients) were used. The visual field was analyzed using an Esterman grid for functional estimation and section paper for gross evaluation. The results were as follows; 1. A decrease in pupillary size eaused not only a decrease in the gross visual field but also a reduction in the functional visual field. 2. The pupillary size did not influence absolute scotoma.
Glaucoma/drug therapy ; Humans ; Pilocarpine/*pharmacology/therapeutic use ; Visual Fields/*drug effects

OBJECTIVETo compare the action of miosis of 1% pilocarpine liposome with 1% pilocarpine solution in rabbits.

METHODS18 white rabbits were randomly divided into 3 groups. Test group received 1% pilocarpine liposome, positive control group received 1% pilocarpine solution, negative control group received liposome. Each eye drop instilled into left eye of rabbits and sterile saline solution instilled into right eye as control. The pupil diameter was measured at time intervals of beginning, 0.25, 0.5, 1, 2, 3, 4, 5, 7 hours.

RESULTSThe mean pupil diameter change of 3 groups in both eyes was not significant (P > 0.05) at beginning. The strongest action of miosis took place 0.25 h in positive control group and 0.5 h in test group after instillation. The dilation of pupil in both groups took place 1 h and 3 h, and the restoration of pupil in both groups took place at 5 h and 7 h. The mean pupil diameter of negative control group was not significant in seven hours.

CONCLUSIONSThe results suggest that 1% pilocarpine liposome improves the bioavailability and prolong the duration of its action.

Animals ; Delayed-Action Preparations ; Female ; Liposomes ; pharmacology ; Male ; Miotics ; pharmacology ; Pilocarpine ; administration & dosage ; pharmacology ; Pupil ; drug effects ; Rabbits ; Random Allocation

OBJECTIVETo study the effect of a microRNA-132 antagonist on lithium-pilocarpine-induced status epilepticus (SE) in young Sprague-Dawley (SD) rats.

METHODSForty-five 3-week-old SD rats were randomly and equally divided into epilepticus model group, microRNA-132 antagonist group, and microRNA-132 antagonist negative control group. The young SD rat model of SE was established using lithium-pilocarpine. For the microRNA-132 antagonist group and the negative control group, pretreatment was performed 24 hours before the model establishment. Behavioral observation was performed to assess the latency of SE and success rate of induction of SE. The scale of Lado was used to evaluate the seizure severity. Electroencephalography (EEG) was used to assess the frequency and amplitude of epileptiform discharges. The mortality rate was calculated in each group.

RESULTSThere was no significant difference in the success rate of induction of SE between the three groups (P>0.05). Compared with the microRNA-132 negative control group and the epilepticus model group, the microRNA-132 antagonist group had significantly prolonged SE latency after model establishment (P<0.05), a significantly lower Lado score of seizure (P<0.05), significantly lower frequency and amplitude of epileptiform discharges on EEG (P<0.05), and a slightly reduced mortality rate.

CONCLUSIONSThe treatment with the microRNA-132 antagonist shows an inhibitory effect on the development and progression of lithium-pilocarpine-induced SE in young SD rats. The inhibition of microRNA-132 is likely to be a potential target or direction for drug treatment of SE.

Animals ; Electroencephalography ; Male ; MicroRNAs ; antagonists & inhibitors ; Pilocarpine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; chemically induced ; drug therapy

PURPOSE: Lithium-pilocarpine induced status epilepticus (LPSE) causes selective and age-dependent neuronal death, although the mechanism of maturation-related injury has not yet been clarified. The activating transcription factor-2 (ATF-2) protein is essential for the normal development of mammalian brain and is activated by c-Jun N-terminal kinase (JNK). It induces the expression of the c-jun gene and modulates the function of the c-Jun protein, a mediator of neuronal death and survival. Therefore, we investigated the expression of c-Jun and ATF-2 protein in the immature and adult rat hippocampus to understand their roles in LPSE-induced neuronal death. MATERIALS AND METHODS: Lithium chloride was administrated to P10 and adult rats followed by pilocarpine. Neuronal injury was assessed by silver and cresyl violet staining, performed 72 hours after status epilepticus. For evaluation of the expression of ATF-2 and c-Jun by immunohistochemical method and Western blot, animals were sacrificed at 0, 4, 24, and 72 hours after the initiation of seizure. RESULTS: Neuronal injury and expression of c-Jun were maturation-dependently increased by LPSE, whereas ATF-2 immunoreactivity decreased in the mature brain. Since both c-Jun and ATF-2 are activated by JNK, and targets and competitors in the same signal transduction cascade, we could speculate that ATF-2 may compete with c-Jun for JNK phosphorylation. CONCLUSION: The results suggested a neuroprotective role of ATF-2 in this maturation-related evolution of neuronal cell death from status epilepticus.
Activating Transcription Factor 2/*metabolism ; Animals ; Antimanic Agents/pharmacology ; Blotting, Western ; Hippocampus/drug effects/*metabolism ; Immunohistochemistry ; Lithium/pharmacology ; Miotics/pharmacology ; Pilocarpine/pharmacology ; Proto-Oncogene Proteins c-jun/*metabolism ; Rats ; Status Epilepticus/*chemically induced

OBJECTIVETo explore the impact of combination use of prostaglandin analogue and cholinergic agonists on main matrix metalloproteinases (MMPs) synthesized by albino rabbit ciliary muscle.

METHODSNormal adult albino rabbits were divided into the control group, 2% pilocarpine group, 0.004% travoprost group and travoprost plus pilocarpine group. Two rabbits in the control group were executed after treated with normal saline for one day. Two rabbits were separately executed on the 7th, 14th and 24th day of the treatment in each drug treated group. In each subgroup ciliary muscle band of 4 eyes was taken and made into homogenate. The MMPs activities of 10 subgroups were assayed by zymography. Bands' intensity which represents the activity of MMPs was measured by the UltraViolet Illumination system.

RESULTSA bright band of MMP-1/2 was showed on each lane at the position corresponding to the molecular weight of 62 kD in the ciliary smooth muscles electrophoresis. When ion Zn and Ca was displaced by MMPs inhibitor EDTA, this bright band disappeared. Compared with the control group, MMP1/2 activity increased by 4.0%, 4.1% and 14.0% after 7, 14 and 24 days of pilocarpine treatment. Corresponding data was 23.2%, 61.7% and 111.5% in the travoprost group and 49.3%, 68.0% and 88.4% in the travoprost plus pilocarpine group.

CONCLUSIONSPilocarpine has little effect on activity of MMP1/2. Travoprost can increase activity of MMP1/2 gradually. Activity of MMP1/2 is rapidly increased by pilocarpine combined with travoprost, but shows small change with the prolonged treatment.

Animals ; Ciliary Body ; drug effects ; enzymology ; Cloprostenol ; analogs & derivatives ; pharmacology ; Matrix Metalloproteinase 1 ; biosynthesis ; Matrix Metalloproteinase 2 ; biosynthesis ; Muscle, Smooth ; drug effects ; enzymology ; Pilocarpine ; pharmacology ; Pilot Projects ; Rabbits ; Travoprost

Animals ; Delayed Rectifier Potassium Channels ; physiology ; Humans ; Membrane Potentials ; drug effects ; Myocardial Ischemia ; pathology ; physiopathology ; Pilocarpine ; pharmacology ; Piperidines ; pharmacology ; Receptor, Muscarinic M3 ; agonists ; antagonists & inhibitors ; physiology ; Signal Transduction ; drug effects

Color Doppler imaging (CDI) was carried out to evaluate the effects of anti-glaucoma drugs on ophthalmic circulation using CDI-derived resistive index (RI) values. CDI was performed on nine Beagle dogs, and RI values were calculated for the medial long posterior ciliary artery before and after the administration of anti-glaucoma drugs. A significant increase in RI values was found after topical administration of levobunolol (p < 0.05) or dipivefrin (p < 0.05). Pilocarpine showed no effects on RI values after topical administration. The results suggest that some anti-glaucoma drugs could affect ophthalmic blood flow.
Adrenergic Agonists/pharmacology ; Animals ; Ciliary Arteries/*drug effects/*ultra ; Dogs ; Epinephrine/analogs & derivatives/therapeutic use ; Eye/*blood supply ; Female ; Glaucoma/*drug therapy ; Levobunolol/therapeutic use ; Male ; Ocular Physiological Phenomena ; Pilocarpine/therapeutic use ; Ultra ; *Vascular Resistance

OBJECTIVETo investigate the effect of rapamycin, an mTOR inhibitor, on learning and memory ability of mice with pilocarpine (PILO)-induced seizure.

METHODSOne hundred and sixty male adult ICR mice were randomly grouped as vehicle control (n=20), rapamycin control (n=20), PILO model (n=40), rapamycin pre-treatment (n=40) and rapamycin post-treatment (n=40). PILO model and rapamycin treatment groups were injected with PILO to induce temporal lobe seizure. Rapamycin was administrated for 3 days before or after seizure. Morris water maze, Y maze and open field were used for the assessment of learning and memory, and FJB and Timm staining were conducted to detect the neuronal cell death and mossy fiber sprouting, respectively.

RESULTSNo significant cell death was observed in the mice with PILO-induced seizure. The learning and memory were impaired in mice 7 to 10 days after PILO-induced seizure, which was evident by prolongation of avoiding latency (P<0.05), decrease in number of correct reaction (P<0.01) and number of crossing (P<0.05). Treatment with rapamycin both pre-and post- PILO injection reversed seizure-induced cognitive impairment. In addition, rapamycin inhibited the mossy fiber sprouting after seizure (P<0.001).

CONCLUSIONRapamycin improves learning and memory ability in ICR mice after PILO-induced seizure, and its mechanism needs to be further studied.

Animals ; Cell Death ; drug effects ; Disease Models, Animal ; Epilepsy ; chemically induced ; drug therapy ; Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred ICR ; Neurons ; drug effects ; pathology ; Pilocarpine ; toxicity ; Sirolimus ; pharmacology

OBJECTIVE: To investigate the efficacy of brain-targeted rapamycin (T-Rap) in treatment of epilepsy in rats. METHODS: Rapamycin nanoparticles targeting brain were prepared. The epilepsy model was induced by injection of pilocarpine in rats. The rats with pilocarpine-induced epilepsy were treated with rapamycin (Rap group) or brain-targeted rapamycin (T-Rap group). Seizure activity was observed by electroencephalography; the effect on mTOR signaling pathway was detected by Western blot; neuronal death and moss fiber sprouting were analyzed by Fluoro-Jade B (FJB) and Timm's staining, respectively. RESULTS: Electroencephalography showed that both preparation of rapamycin significantly reduced the frequency of spontaneous seizures in rats, and the effect of T-Rap was stronger than that of conventional rapamycin (<0.05). Western blot showed that the phosphorylation levels of S6K and S6 in T-Rap group were lower than those in Rap group (all <0.05), indicating that T-Rap had a stronger inhibitory effect on mTOR signaling pathway. FJB staining showed that T-Rap significantly decreased neuronal death, but there was no significant difference as compared with Rap group. Timm's staining showed that both preparations of rapamycin significantly reduced the germination of mossy fibers, while the effect of T-Rap was more pronounced than Rap group (<0.05). The inhibition of body weight gain of T-Rap group was less than that of Rap group (<0.05). CONCLUSIONS T-Rap has a better therapeutic effect on epilepsy than conventional rapamycin with a less adverse effects in rats.
Animals ; Brain ; drug effects ; Disease Models, Animal ; Epilepsy ; chemically induced ; drug therapy ; Neurons ; drug effects ; Pilocarpine ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Sirolimus ; pharmacology ; therapeutic use ; Treatment Outcome

Cystic fibrosis (CF) is inherited as an autosomal recessive trait, and the mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene contributes to the CF syndrome. Although CF is common in Caucasians, it is known to be rare in Asians. Recently, we experienced two cases of CF in Korean children. The patients were girls with chronic productive cough since early infancy. Chest computed tomography showed the diffuse bronchiectasis in both lungs, and their diagnosis was confirmed by the repeated analysis of a quantitative pilocarpine iontophoresis test (QPIT). The sweat chloride concentrations of the first patient were 108.1 mM/L and 96.7 mM/L. The genetic analysis revealed that she was the compound heterozygote of Q1291X and IVS8 T5 -M470V. In the second case, the sweat chloride concentrations were 95.0 mM/L and 77.5 mM/L. Although we performed a comprehensive search for the coding regions and exonintron splicing junctions of CFTR gene, no obvious disease-related mutations were detected in the second case. To our knowledge, this is the first report of CF in Korean children identified by a QPIT and genetic analysis. The possibility of CF should be suspected in those patients with chronic respiratory symptoms even in Korea.
Blood Pressure ; Bronchiectasis/diagnosis/pathology ; Child ; Cough ; Cystic Fibrosis/*diagnosis/*genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; DNA Mutational Analysis ; Exons ; Female ; Heterozygote ; Humans ; Introns ; Iontophoresis/*methods ; Korea ; Lung/pathology/radiography ; Muscarinic Agonists/*pharmacology ; Mutation ; Pancreas/pathology ; Pedigree ; Phenotype ; Pilocarpine/*pharmacology ; Polymorphism, Genetic ; Research Support, Non-U.S. Gov't ; Sinusitis/diagnosis/pathology ; Sweat ; Time Factors ; Tomography, X-Ray Computed