Cocaine self-administration on a hold-down schedule of reinforcement in rats

Rationale and objective  Although many contingencies operating in the natural environment include continuous dimensions of responses and reinforcers, previous studies of drug self-administration have almost exclusively used discrete dimensions of responses (e.g., a lever press) and reinforcers (e.g., 1.0 mg/kg/injection cocaine). Therefore, the present study provides an initial examination under experimental conditions with both responses and reinforcers measured along continuous dimensions. Materials and methods  Cocaine-maintained responding was studied in rats under a novel, hold-down schedule of reinforcement wherein the duration of the response was directly related to the magnitude of the reinforcer. These conditions were established by activating the syringe pump when the lever was pressed down and turning the pump off when the lever was released. The concentration of cocaine available in the syringe was varied across sessions. Results  Cocaine self-administration was readily maintained under these conditions and remained stable across sessions. Responding was concentration dependent, with the number of responses and total duration of the response inversely related to concentration, and overall session intake of cocaine was stable across concentrations. In general, the duration of the responses were less than 0.5 s and did not vary as a function of concentration. Conclusions  Stability of responding under these schedule conditions was acquired quickly. This schedule of reinforcement may be useful for comparing across drug classes, can be extended for use with other types of responses and reinforcers, and may be more representative of the natural world where response-reinforcer contingencies are more likely to be experienced along continuous, rather than discrete, dimensions. Drake Morgan and Yu Liu contributed equally to this publication.     

Synthesis of some novel oxazolidinone-thiazole hybrids as potential antimicrobial,antioxidant and UV mediated DNA damage protecting agents

In search of a new class of biologically active agents, some novel oxazolidinone-thiazole hybrids 4a–m have been synthesized and characterized on the basis of a combined use of infrared, NMR (¹H, ¹³C) spectroscopy, mass spectrometry and elemental analysis. All compounds were evaluated for their antimicrobial, antioxidant and ultraviolet mediated DNA damage protective activity. Among the series, compound 4i emerged as the most potent antimicrobial agent, particularly, against Bacillus subtilis, Candida albicans and Saccharomyces cerevisiae in comparison to the standard drugs, Ciprofloxacin (antibacterial) and Amphotericin-B (antifungal). Other promising antimicrobial agents including the compounds 4f–h. In addition, all compounds 4a–m were found to show very high DNA damage protecting ability under ultraviolet irradiation. The antioxidant study revealed that the compounds 4d and 4j were found as the most potent antioxidants as compared to ascorbic acid, a reference compound considered in the study.     

Nasal absorption studies of granisetron in rats using a validated high-performance liquid chromatographic method with mass spectrometric detection

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although forms of the drug are commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liq uid chromatography method with mass spectrometric detection (LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. Granisetron was separated in a reverse-phase C-18 column without interference from other components of plasma. This method involves a rapid assay for the determination of granisetron in a small volume of plasma with a run time of 12 min using ondansetron as an internal standard. Data were acquired in the electrospray ionization (ESI) mode with positive ion detection and application of single ion recording (SIR). Granisetron and ondansetron were detected at m/z values of 313.2 and 294.2, respectively. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. To date, the first pharmacokinetic study after intranasal administration of granisetron was performed and some pharmacokinetic parameters were presented in this paper. Granisetron was found to be well absorbed through nasal route and the bioavailability of this drug following nasal administration was comparable with that of intravenous administration.     

The effect of sodium valproate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.     

Effect of Iontophoresis in Combination with Ionic Enhancers on the Lipid Structure of the Stratum Corneum: An X-ray Diffraction Study

Pharmaceutical Research -     

Sequential effects of cadmium on genotoxicity and lipoperoxidation in <Emphasis Type="Italic">Vicia faba</Emphasis> roots

Kinetics of stress responses to Cd exposure (50, 100 and 200 μM) expanding from 12 to 48 h were studied in roots of hydroponically cultivated-Vicia faba seedlings. The heavy metal induced toxicity symptoms and growth arrest of Vicia roots gradually to the Cd concentration and duration of the treatment. The intracellular oxidative stress was evaluated with the H₂O₂ production. The H₂O₂ content increased gradually with the sequestered Cd and root growth inhibition. Lipid peroxidation—evidenced by malondialdehyde (MDA) content and Evans blue uptake—and genotoxicity—evidenced by mitotic index (MI) and micronuclei (MCN) values—were concomitantly investigated in root tips. By 12 h, root meristematic cells lost 15% of their mitotic activity under 50 or 100 μM Cd treatment and 50% under 200 μM Cd treatment and led cells with MCN, while the MDA content and Evans blue absorption were not affected. The loss of membrane integrity occurred subsequently by 24 h. The increase in MDA content in root cells treated with 50, 100 and 200 μM Cd was significantly higher than the control. By 48 h, the MDA content increased 134, 178 or 208% in root cells treated with 50, 100 and 200 μM Cd, respectively. The Evans blue absorption was also affected by 24 h in roots when treated with 200 μM Cd and gradually increase by 48 h with the Cd concentration of the treatment. The decrease of mitotic activity triggered by 12 h was even higher by 24 h and the MI reduced to 44, 56 or 80% compared to the control in the three different Cd concentrations tested. The different kinetics of early in vivo physiological and cytogenetic responses to Cd might be relevant to the characterization of its toxicity mechanisms in disrupting primarily the mitosis process.     

Wavefront analysis of acrylic spherical and aspherical intraocular lenses

PURPOSE: To compare higher order wavefront aberrations in eyes implanted with acrylic aspherical intraocular lenses (IOLs) with a modified prolate anterior surface with conventional acrylic spherical IOLs by using the optical path difference method. METHODS: In a nonrandomized parallel cohort investigation, 36 eyes of 31 patients implanted with aspherical IOLs (Tecnis ZA9003) and 37 eyes of 23 age-matched patients implanted with spherical IOLs (SENSOR AR40e) were evaluated with a wavefront analyzer (OPD-Scan II) preoperatively and 1 month after surgery. The higher order aberrations for a 4.0-mm pupil diameter were expanded into Zernike's polynomial expression. Coma aberration, spherical aberration, and total higher order aberrations were evaluated as root mean square values. RESULTS: Postoperatively, coma and total higher order aberrations of spherical and aspherical IOLs significantly improved in both eyes. Spherical aberration improved in eyes with aspherical IOLs only (P < 0.01). CONCLUSION: After implantation of acrylic aspherical IOLs, postoperative higher order aberrations were not necessarily lower than after implantation of acrylic spherical IOLs, but compared with levels following implantation of acrylic spherical IOLs, a significant reduction in spherical aberration was achieved.     

Pathological findings of multifocal choroiditis with panuveitis and punctate inner choroidopathy

PURPOSE: To compare the pathological findings between multifocal choroiditis with panuveitis (MCP) and punctate inner choroidopathy (PIC). METHODS: Fourteen eyes of 14 patients clinically diagnosed as having MCP or PIC who underwent surgical excision of choroidal neovascularization (CNV) were studied. Immunohistochemical findings of the excised CNV in MCP (eight eyes) and PIC (six eyes) cases were compared. Antibodies against vascular endothelial growth factor (VEGF), CD68, CD3, and CD20 were used as primary antibodies. RESULTS: Expression of VEGF and CD68 in the CNV was observed in all MCF and PIC cases. In three of eight eyes with MCP, intraocular inflammatory findings were found clinically, while immunohistochemical study demonstrated infiltration of CD20-positive B lymphocytes in the CNV. No B lymphocyte infiltration was found in the six eyes with PIC. No differences in pathological findings were found between the five MCP eyes without intraocular inflammation and the six PIC eyes, with all eyes showing no B lymphocyte infiltration. CONCLUSIONS: In MPC cases showing clinical inflammatory findings, infiltration of B lymphocytes was also observed histopathologically, suggesting that the presence of inflammatory cells in the anterior chamber or vitreous body clinically is an indicator of active inflammatory CNV. However, this study clarifies that MCP eyes without intraocular inflammation and PIC eyes are not different in histopathological findings.     

Occurrence of <Emphasis Type="Italic">Demodex</Emphasis> species in patients with blepharitis and in healthy individuals: a 10-year observational study

Purpose

Two Demodex species (eyelash mites)—D. folliculorum and D brevis—are believed to be associated with human skin and eye diseases. However, the clinical significance of infection with Demodex species remains controversial.

Study design

The aim of this study was to estimate the prevalence of ocular demodicosis in patients with blepharitis as compared with the prevalence in the healthy population in Poland.

Methods

This case-control prospective study was carried out from 2007 to 2016. The enrolled patients (668) were divided into 2 groups: the study group, comprising 553 patients with blepharitis (349 women and 204 men, aged 17–88 years), and the control group, comprising 115 healthy volunteers without a history of ocular pathologies (78 women and 37 men, aged 17–88 years). A sample of 10 eyelashes was taken aseptically from each eye of the examined person and later studied under a light microscope.

Results

Demodex species were found in 62.4% (345/544) of the patients in the study group and in 24.3% (28/100) of the controls (P = .001, OR = 0.006). The overall prevalence was 55.8% (373/668) in all the examined participants. The presence of Demodex infection increased with age in both groups. No association of Demodex infection with gender was found (119/204 vs 226/349; P > .05, OR 1.086). A high mean number of mites was present more frequently in patients aged older than 50 years and in those who complained especially about itching (P < .05).

Conclusion

The prevalence of ocular demodicosis is significantly correlated with blepharitis and increases with age.