Involvement of l-arginine-nitric oxide pathway in anxiolytic-like effects of zinc chloride in rats.

PURPOSE: Zinc is crucial for normal development of the brain, and Zinc deficiency has been shown to associate with neurological disorders (e.g. anxiety) through interactions with several neurotransmitter systems such as nitric oxide (NO). In this regard, our study aimed to evaluate the possible involvement of l-arginine NO pathway on anxiolytic effects of zinc in adult male rats. METHODS: Zinc chloride at doses of 2.5 and 10mg/kg (intraperitoneal or ip) or saline (1ml/kg, ip) were injected 30min before the anxiety test. Zinc administrated rats (10mg/kg) were pre-treated with intra-CA1 microinjection of l-arginine in sub-effective dose of 1µg/rat (dorsal hippocampus, vehicle: saline1µl/rat). In addition, zinc chloride and NG-nitro-l-arginine methyl ester (l-NAME) were intraperitoneally co-administrated in sub-effective doses of 2.5mg/kg and 80mg/kg, respectively. The percentage of open arm time (OAT%), percentage of open arm entry (OAE%), as measures of anxiety, and total number of arm entries, as measures of locomotor activity, were recorded. RESULTS: Treatment with zinc (10mg/kg) markedly produced an increase in OAT% and OAE% in the Elevated plus maze test (EPM). A decrease of OAT% and OAE% was shown in groups which received zinc (10mg/kg) and l-arginine (1µg/rat) concomitantly as compared to the control group. Moreover, an increase of OAE% was revealed in the group exposed to Zinc (2.5mg/kg) and l-NAME (80mg/kg) co-administration. Although, Two-way ANOVA showed no significant differences of anxiety indices in rats received drug+zinc chloride in compare to the zinc pretreated with saline group. CONCLUSION: Anxiolytic- like effect of zinc reversed by nitric oxide precursor l-arginine. Additionally, the synergistic effects of l-NAME and ZnCl2 were shown in the EPM. Thus our findings suggest that at least in part the anxiolytic effects of zinc can be mediated through the nitric oxide system.

Effect of Intra CA1 and Intraperitoneal Administration of Opioid Receptor Modulating Agents on The Anxiolytic Properties of Nano and Conventional ZnO in Male Rats.

OBJECTIVE: Nano components are today's new wonder material. However, the safety or toxicity of these components in humans is not yet clear. In a previous study we indicated that nano ZnO (nZnO) has a stronger anxiolytic effect compared to the conventional ZnO (cZnO). The present study was designed to evaluate the intraperitoneal administration of an opioidergic receptor agonist and antagonist of as well as the intra CA1 administration of an opioidergic receptor antagonist on the anxiolytic properties of nano and conventional ZnO in adult male Wistar rats. MATERIALS AND METHODS: In this experimental study, rats received drugs via two modes of injection; intraperitoneal (IP.) and intra CA1 (intra hippocampus, CA1 area). Firstly, nZnO (5, 10, 20 mg/kg), cZnO (5, 10, 20 mg/kg), morphine 6 mg/kg, and naloxone 1 mg/kg were injected IP and naloxone 1µg/rat was injected intra CA1. Subsequently, morphine and na- loxone (IP and intra CA1) were co-injected with the effective dose of nZnO and cZnO. An elevated plus maze was used to evaluate anxiety related behavior and anxiety parameters 30 minutes after the second injection. RESULTS: The results indicated that the anxiolytic effects of nZnO 5 mg/kg and cZnO 10 mg/kg were equal. When injected intraperitoneally, naloxone increased anxiety but did not inhibit the anxiolytic effect of nZnO and cZnO. The anxiolytic effects of morphine potentiated the anxio- lytic effects of ZnO, particularly nZno. When introduced via intra CA1 injection naloxone alone had no effect on anxiety behaviors and did not inhibit the anxiolytic effect of nZnO. CONCLUSION: It seems that the opioidergic system activity involved in the anxiolytic effect of nano and conventional ZnO may operate through shared and unshared pathways.

Effects of nano and conventional zinc oxide on anxiety-like behavior in male rats.

OBJECTIVES: Current drug therapies for psychological disorders, such as anxiety, are not as effective as expected, and it has been shown that zinc supplements, such as zinc oxide (ZnO), can influence anxiety. ZnO nanoparticles (ZnO NPs) are among the most used nanomaterials produced and applied in many products. MATERIALS AND METHODS: This study investigated the effects of ZnO NPs in comparison with conventional ZnO (cZnO) on anxiety-like behaviors. Adult male Wistar rats were divided into groups: Control (receiving saline 0.9%), ZnO NPs (5, 10, 20 mg/kg), and cZnO (5, 10, 20 mg/kg). All drugs were dispersed in saline 0.9%, and 30 minutes after intraperitoneal (i.p.) injection of drugs, elevated plus maze apparatus was used to evaluate anxiety. RESULTS: ZnO NPs (5 mg/kg) and cZnO (10 and 20 mg/kg) significantly increased the percentage of time spent in open arm (open arm time % OAT) compared with the control group (P < 0.05). This indicates the anxiolytic effect of such components; in addition, ZnO NPs (20 mg/kg) reduced locomotor activity (P < 0.05). Serum zinc concentration increased by both anxiolytic dose of components (from 1.75 ± 1.07 (mg/l) in control group to 5.31 ± 0.53 (mg/l) in ZnO NPs (5 mg/kg) and 10.38 ± 0.90 (mg/l) in cZnO (10 mg/kg) groups). Also, all doses increased serum pH (from 7.3 ± 0.05 in control group to 8.1 ± 0.05 in ZnO NPs (5 mg/kg) and 8.05 ± 0.01 in cZnO (10 mg/kg) groups and kept them constant after 24 hours. CONCLUSION: Results indicate that the anxiolytic effect of ZnO NPs is much higher than its conventional form, but the introduction of ZnO NPs, as a new drug for treatment of anxiety disorder, needs further investigations.

Involvement of basolateral amygdala GABAA receptors in the effect of dexamethasone on memory in rats.

In this study we investigated whether GABA(A) receptors of the basolateral amygdala (BLA) interact with the effect of dexamethasone on the retrieval stage of memory. Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery. The animals were trained in step-through apparatus by induction of electric shock (1.5 mA, 3 s) and were tested for memory retrieval after 1 d. The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory. Administration of dexamethasone (0.3 and 0.9 mg/kg, subcutaneously (s.c.)), immediately after training, enhanced memory retrieval. This effect was reduced by intra-BLA microinjection of muscimol (0.125, 0.250 and 0.500 µg/rat), when administered before 0.9 mg/kg of dexamethasone. Microinjection of bicuculline (0.75 µg/rat, intra-BLA) with an ineffective dose of dexamethasone (0.1 mg/kg, s.c.) increased memory retrieval. However, the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes. Our data support reports that dexamethasone enhances memory retrieval. It seems that GABA(A) receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.

Current appraisal of conjunctival melanocytic tumors: classification and treatment.

Conjunctival melanocytic tumors represent a spectrum of pigmented tumors that include benign, premalignant and malignant tumors. Conjunctival nevi are the most common pigmented tumors and are typically found in the interpalpebral bulbar conjunctiva. These lesions usually contain fine clear cysts on slit lamp biomicroscopy. Primary acquired melanosis includes lesions from increased melanin pigmentation without proliferation of melanocytes to melanoma in situ. In the new classification system, the idea is to use the term 'primary acquired melanosis' only as a clinical description, highlighting the fact that the biologic behavior of acquired melanotic lesions cannot be predicted solely based upon clinical grounds without histopathologic examination. Conjunctival melanoma represents only 5% of all melanomas arising in the ocular region and is associated with a high mortality rate. The management of primary acquired melanosis, nevi and conjunctival melanomas involves various modalities used either alone or concomitantly depending on the size and extent of the lesion.

Comparison of reading performance after bilateral implantation of multifocal intraocular lenses with +3.00 or +4.00 diopter addition.

PURPOSE: To compare reading ability after cataract surgery and bilateral implantation of multifocal intraocular lenses (IOLs) with a +3.00 diopter (D) addition (add) or a +4.00 D add. SETTING: Department of Ophthalmology, University of São Paulo, São Paulo, Brazil. DESIGN: Prospective comparative study. METHODS: Patients scheduled for cataract surgery were randomly assigned to bilateral implantation of an aspheric AcrySof ReSTOR multifocal IOL with a +3.00 diopter (D) addition (add) or a +4.00 D add. The reading speed, critical print size, and reading acuity were measured binocularly with best correction using MNREAD acuity charts 6 months after surgery. Patients were tested with the chart at the best patient-preferred reading distance and at 40 cm. Binocular uncorrected and best distance-corrected visual acuities at far and near were also measured. RESULTS: The study enrolled 32 patients. At the best reading distance, the results were similar between the 2 IOL groups in all reading parameters. When tested at 40 cm, reading speed at all print sizes from 0.3 to 0.0 (all P<.001), critical print size (P<.001), and reading acuity (P = .014) were statistically significantly better in the +3.00 D IOL group than in the +4.00 D IOL group. Uncorrected and corrected visual acuities at far and near were similar between the 2 groups. CONCLUSION: Although the 2 IOL groups had similar performance in reading parameters, patients had to adjust to their best reading distance. The +3.00 D IOL performed better than the +4.00 D IOL at 40 cm.

The role of hippocampal nitric oxide (NO) on learning and immediate, short- and long-term memory retrieval in inhibitory avoidance task in male adult rats.

There is impressive amount of evidence suggesting the involvement of nitric oxide (NO) in hippocampal synaptic plasticity and consequently learning and memory. Hippocampus is a brain region which is widely implicated in several types of learning and memory formation, including inhibitory avoidance learning. Since the CA1 region of hippocampus has shown nitric oxide synthase (NOS) activity, inhibition of the NOS enzymes can modulate hippocampal function, hence affecting memory processes. Therefore, we conducted series of experiments to further investigate the role of NO on inhibitory avoidance short- and long-term memory in rats. For this purpose, male Wistar rats were divided into 15 groups (n=10), and bilaterally implanted with guide cannulae aimed at the CA1 region of hippocampus. Animals received pre-training, post-training and pre-retrieval injections of vehicle (saline) or different doses of L-NAME (5, 10 and 15 microg/0.5 microl/side) or l-arginine (alone or in combination with L-NAME), tested for immediate, short- and long-term memory retention in an inhibitory avoidance task. Our results indicated that step-through latency (STL) of short- and long-term memory retention test was significantly reduced in L-NAME treated rats (15 microg/0.5 microl for immediate and short-term memory; 10 microg/0.5 microl for long-term memory), as compared to that of control group. Results also revealed that, L-arginine produced no any significant effect on STL, however could reverse the effect of L-NAME on memory. Our results also showed that, blocking of NO signaling immediately after training had no effect on either short- or long-term memory, indicating that NO release only during training, and not during consolidation, plays a role in memory formation. Together, our findings suggest that NO synthase inhibition by L-NAME can induce impairments in immediate, short- and long-term memories of inhibitory avoidance task, and these impairments are dependent on the learning and memory processes at which NOS inhibited.

Intra hippocampal injection of testosterone impaired acquisition, consolidation and retrieval of inhibitory avoidance learning and memory in adult male rats.

The hippocampus is essentially involved in learning and memory, and is known to be a target for androgen actions. Androgen receptors are densely expressed in CA1 of rat hippocampus, and mediate the effects of testosterone (T) on learning and memory. T depletion or administration can modulate neural function and cognitive performance. We conducted series of experiments to further investigate the effect of castration or intra hippocampal injection of T on acquisition, consolidation and retrieval of inhibitory avoidance learning and memory. Male adult rats were bilaterally cannulated into CA1 of hippocampus, and then received T (1, 10, 20, 40 and 80mug/0.5mul/side) or vehicle (DMSO), 30min before training, immediately after training and 30min before retrieval in inhibitory avoidance task. Castration was made by gonadectomy of male rats and behavioral tests performed 4 weeks later. Our results showed that gonadectomy of male rats did not influence performance on inhibitory avoidance task, as compared to sham-operated rats. We have also found that pre-training, post-training and pre-retrieval intra CA1 injections of T significantly decreased step-through latencies in inhibitory avoidance learning at doses 1 and 80, 20, and 20 and 40mug/0.5mul/side, respectively. The data suggest that intra CA1 administration of T could impair learning and memory acquisition, consolidation and retrieval, while systemic androgen's depletion have no effect on memory, in inhibitory avoidance task.

The effect of intrahippocampal injections of ritanserin (5HT2A/2C antagonist) and granisetron (5HT3 antagonist) on learning as assessed in the spatial version of the water maze.

5HT(2A/2C) and 5HT(3) receptors have an important role in cognitive behavior specially in spatial learning and memory but the literature concerning the role of these receptors in hippocampus in cognition remains controversial. In the present study a 5HT(2A/2C) antagonist ritanserin (0, 2, 4, 8 microg/0.5 microl) and a 5HT(3) antagonist granisetron (0.0, 0.05, 0.25, 0.5 microg/0.5 microl) were injected bilaterally into the CA1 region of rat hippocampus, 20 min before each training session in Morris Water Maze (MWM) task. Compare with control group, ritanserin (4 microg/0.5 microl) significantly reduced the escape latency and traveled distance of swimming to platform, but granisetron (0.25 microg/0.5 microl) significantly increased those parameters. Both drugs had no effect on escape latency and traveled distance of a non-spatial visual discrimination task. These results suggest a differential role of 5HT(2A/2C) and 5HT(3) receptors during spatial learning that ritanserin improves rat performance in spatial discrimination task whereas granisetron impairs it.

Diagnostic yield for neuroimaging in patients with unilateral eye or facial pain.

BACKGROUND: The neuroimaging evaluation of isolated pain in or around the eye has not been studied previously. We report the low diagnostic yield of neuroimaging in patients who have a normal ocular examination and unilateral eye pain or facial pain predominantly affecting the eye. METHODS: Retrospective review of patients referred to 3 neuro-ophthalmology practices for unexplained pain in or around the eye. Inclusion criteria were adults with isolated unilateral eye/facial pain, neuroimaging, and a normal eye exam. Ex-clusion criteria were symptoms typical of a defined pain syndrome (e.g., trigeminal neuralgia or giant cell arteritis), and exam findings that would account for the pain. RESULTS: One hundred and twenty-seven (127) of the 760 reviewed patients met study criteria, and underwent MRI (75) or CT (34) scans, or both (18). Imaging was normal in 106 (83%). Abnormalities (n = 21) on imaging (17%) included nonspecific T2-weighted hyperintensities (10), sinusitis (5), superior ophthalmic vein enlargement (1), pontine lacunar infarct (1), Chiari malformation (1), thalamic mass (1), old occipital stroke (1), and focal enlargement of the third cranial nerve (1). INTERPRETATION: Although imaging showed abnormalities in 17% of cases of isolated pain in or around the eye, only 2 abnormalities were believed to be possibly related to the pain and only 1 case was probably related. The diagnostic yield of neuroimaging in patients with a normal examination and isolated, unilateral eye/facial pain referred to a neuro-ophthalmologist is low.