Intraocular acyclovir levels after subconjunctival and topical administration.

Substantial levels of acyclovir were detected in the aqueous and vitreous of New Zealand rabbits at various time intervals following subconjunctival injection. Intravitreal penetration of acyclovir after topical application was poor.     

Hyperaemia in rat neocortex produced by acute exposure to methylenedioxymethamphetamine

Cerebral blood flow and glucose utilization were measured in rat neocortex, hippocampus and striatum following methylenedioxymethamphetamine injection (5 mg/kg, i.v.), using the tracers [¹⁴C]iodoantipyrine and [¹⁴C]2-deoxyglucose, respectively. In control rats, blood flow was coupled to glucose metabolism, but in methylenedioxymethamphetamine-treated rats, marked hyperperfusion was measured in frontal and parietal cortex with no change in glucose use. This suggests that methylenedioxymethamphetamine has the potential to disrupt cerebrovascular control.     

Removal of the endothelial layer in perfused mesenteric vascular bed of the rat.

The endothelial layer was removed from the isolated mesenteric vascular bed of the rat by perfusion with hypotonic Tyrode solution for 12.5 min. This procedure damaged more than 95% of the endothelial cells. After endothelial removal, the response to norepinephrine was significantly enhanced, whereas the relaxation induced by acetylcholine (ACh) was completely abolished. The results of this work show that perfusion with hypotonic solutions provides a reliable method of endothelial removal in isolated perfused vascular beds, allowing the study of endothelial-dependent vascular responses.     

Steroid glaucoma: corticosteroid-induced ocular hypertension in cats.

This study was undertaken to develop a feline model of corticosteroid-induced ocular hypertension. In the first experiment, eight cats were selected whose intraocular pressure (17 +/- 0.4 mmHg) was consistently below the mean baseline intraocular pressure of our colony (24 +/- 0.5) during the preceding 2 months. Unilateral twice or thrice daily topical application of 10 microliters 1% dexamethasone sodium phosphate caused a gradual intraocular pressure increase that became significant (P less than 0.05) within 2-3 weeks. There was no significant change in body weight, but several eyes developed cataracts. Similar results were obtained with treatment of normotensive cat eyes with dexamethasone, or with 1.0% prednisolone acetate (PredForte) twice a day. Topical application of PGF2 alpha-1-isopropyl ester (0.1 or 0.25 microgram PG equivalent) to such steroid-treated eyes yielded significant intraocular pressure reduction and pupillary miosis, similar in magnitude to those exhibited by normal eyes. When dexamethasone treatment was reduced to once daily, after prolonged twice daily treatment, intraocular pressure decreased only slightly within 10 days. When dexamethasone treatment was stopped, intraocular pressure declined to normal levels within 6-7 days. These findings show that adult cat eyes develop steroid-induced ocular hypertension that is maintained and reversible. As opposed to previous findings on rabbits, steroid-induced feline ocular hypertension appears to be a good model for this clinical condition and may be suitable for the testing of potential glaucoma drugs.     

Prognostic value of preoperative tests in the surgical treatment of ascites with the implant of Le Veen shunts in cirrhotics.

In the period of January 1978 to October 1988, 32 Le Veen shunts (LVS) were implanted in 20 patients, out of which 16 were alcoholic cirrhotics and 4 postnecrotic cirrhotics. In the present study, we correlated preoperative laboratory data of these patients with their postoperative evolution, comparing the clinical results of patients who survived more than 30 days (13 patients = 65%) with the results of those who died within the same period (7 patients = 35%). For that matter, 14 laboratory tests were performed in order to measure the serum levels of hematocrit, hemoglobin, urea, creatinine, sodium, potassium, bilirubin, albumin, AST, ALT, alkaline phosphatase, fibrinogen, gamma GT and prothrombin activity. After statistical analysis, we observed that 6 of the 14 tests performed could be considered of prognostic value in the following decreasing order of importance: fibrinogen, alkaline phosphatase, prothrombin activity, urea, gamma GT and bilirubin. We observed that all the 7 patients who died prematurely presented 3 or more of these levels altered, when compared with standard values. Based on these data, we concluded that serum levels of fibrinogen, alkaline phosphatase, urea, gamma GT, bilirubin and activity of prothrombin proved to be important factors in determining the prognosis of immediate survival in cirrhotic patients who underwent LVS implantation. We also concluded that when 3 or more of these factors are altered, the implant of LVS is contraindicated, whatever clinical criteria for indication and contraindication were taken into account.     

Developmental expression of estrogen receptor mRNA in the rat cerebral cortex: a nonisotopic in situ hybridization histochemistry study.

The distribution of estrogen receptor mRNA expression was studied in the developing rat cerebral cortex by in situ hybridization histochemistry. We used a specific, nonisotopically (digoxigenin) labeled, synthetic oligodeoxyribonucleotide complementary to a 48 base sequence in the region of the estrogen-binding domain of rat uterine estrogen receptor cDNA. During development, estrogen receptor mRNA was observed in all forebrain regions previously reported to bind estrogen, as determined by steroid autoradiography or nuclear binding assay. In the developing cerebral cortex, estrogen receptor mRNA was extensively expressed in the ventricular zone, primitive plexiform layer, and immature cortical plate at least as early as embryonic day 16. During the first 3 postnatal weeks, cortical mRNA expression was increasingly restricted to the upper third of the cerebral cortex and to the neurons of the cortical subplate (layer VIb/VII) and decreased to low levels by postnatal day 28. In the cerebral cortex, the spatial distribution of estrogen receptor mRNA expression overlapped that reported for the encoded protein. The extensive distribution of estrogen receptor mRNA throughout the late prenatal and early postnatal cerebral cortex points to an important role for estrogen in the differentiation and maturation of the cerebral cortex.     

Modeling the current distribution during transcranial direct current stimulation.

OBJECTIVE: To investigate the spatial distribution of the magnitude and direction of the current density in the human head during transcranial direct current stimulation (tDCS). METHODS: The current density distribution was calculated using a numerical method to implement a standard spherical head model into which current was injected by means of large electrodes. The model was positioned in 'MNI space' to facilitate the interpretation of spatial coordinates. RESULTS: The magnitude and direction of the current density vector are illustrated in selected brain slices for four different electrode montages. Approximately half of the current injected during tDCS is shunted through the scalp, depending on electrode dimension and position. Using stimulating currents of 2.0 mA, the magnitude of the current density in relevant regions of the brain is of the order of 0.1 A/m2, corresponding to an electric field of 0.22 V/m. CONCLUSIONS: Calculations based on a spherical model of the head can provide useful information about the magnitude and direction of the current density vector in the brain during tDCS, taking into account the geometry and position of the electrodes. Despite the inherent limitations of the spherical head model, the calculated values are comparable to those used in the most recent in vitro studies on modulation of neuronal activity. SIGNIFICANCE: The methodology presented in this paper may be used to assess the current distribution during tDCS using new electrode montages, to help optimize montages that target a specific region of the brain or to preliminarily investigate compliance with safety guidelines.     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.