Chemical and pharmacological research on derivatives of 1H-naphtho/2,1-b/pyran. V. Behavior of some 1-oxo-3-dialkylamino-1H-naphtho/2,1-b/pyrans substituted in the Mannich reaction]

1-Oxo-3-dialkylamino-1H-naphtho [2,1-b] pyrans substituted in positions 5, 8 or 9 with halogen, alkyl, alkoxycarbonyl, hydroxyl, methoxyl, by the Mannich reaction will yield the corresponding 2-dialkylamino-methyl derivatives when a correct amount of acetic acid is present in the reaction mixture. Excess acid will give rise to the formation of substituted 1-oxo-2-[(1'-oxy-3'-oxo-3'H-naphtho [2',1'-b']pyran-2'-yl)methyl]-3-dialkylamino-1H-naphtho [2,1-b] pyrans when the group in the 3 position is dimethylamino or N-pyrrolidyl. In a few cases Mannich bases were accompanied by an appreciable quantity of substituted 2,2'-methylenebis (1-oxo-3-dialkylamino-1H-naphtho-E12,1-B] PYRANS). Therefore, these compounds were synthesized with excellent yields by treating Mannich bases with acetic anhydride. The behavior of some compounds in the acidic hydrolysis was also considered. Some Mannich bases of 1-oxo-3-dialkylamino-9 methoxy-1H-naphtho-[2,1-b] pyrans showed a more specific anticonvulsant activity than the parent compounds.     

Apparatus bias and the use of light and texture in place conditioning

In a typical conditioned place preference (CPP) preparation, animals alternately experience drug and vehicle effects in distinct chambers of an apparatus, spending more time in the drug-paired chamber post-conditioning. However, if all animals prefer the same chamber before conditioning, data interpretation may be compromised. Unbiased apparatus has been systematically validated with ethanol in mice ([Cunningham, C.L., Feree, N.K., Howard, M.A. Apparatus bias and place conditioning with ethanol in mice. Psychopharmacology (Berl) 2003;170:409-422]); the present study sought to identify and eliminate bias in a standard black-and-white apparatus and validate that apparatus for CPP with morphine and cocaine in rats. Apparatus bias was assessed in 24 adult female Sprague-Dawley rats. Subjects preferred the black chamber under bright lighting conditions, with no preference in the dark. Subjects then underwent a counterbalanced CPP regimen to 5 mg/kg SC morphine (n=12) or 20 mg/kg IP cocaine (n=12) using only tactile conditioned stimuli. Significant absolute preferences for the drug-paired chamber were produced by both drugs, with no effect of drug-paired chamber assignment on CPP expression; vehicle-treated controls (n=12) showed no preferences. Bias-free CPP to morphine and cocaine using standard apparatus in rats is possible. Implications for place conditioning are discussed, including the potential value of systematically exploiting apparatus bias in addition to eliminating it.     

Neonatal Volkmann's compartment syndrome. A report of two cases

Neonatal Volkmann's compartment syndrome is a rare entity. This diagnosis may be suspected when a case presents cutaneous damage associated with poor hand and wrist function after delivery. We present two such cases of neonatal Volkmann compartment syndrome with long term clinical and x-ray follow-up. In our patients, a hand surgeon was not consulted in the perinatal period and early fasciotomy was not performed. No particular aetiology or associated cerebrovascular accident was found. A series of operations was necessary in order to improve function of the hand. Neonatal Volkmann compartment syndrome must be recognised early in order to enable further investigation of any underlying condition and to perform early surgical decompression. Long term clinical and x-ray follow-up is necessary to prevent and treat wrist deformation and finger contractures.     

Erythropoietin levels in children and adolescents with inflammatory bowel disease

Iron deficiency anemia (IDA) and anemia of chronic disease (CDA) are often encountered in patients with inflammatory bowel disease (IBD). Inadequate intake or loss of iron is a clear cause of IDA, but mechanisms of CDA induction are multifactorial and involve erythropoiesis disturbance due to circulating inflammation mediators. The authors investigated erythropoietin (Epo) levels in children and adolescents with IBD and correlated them to disease activity, with the aim of gaining an improved understanding of the role of Epo in CDA. Thirty-three patients with IBD were examined (18 boys, 15 girls) ages 4 to 15 years (median 11 years). Two study groups related to the disease activity were formed: group A, those with active disease (n = 21), and group B, those in remission (n = 12). Epo levels were measured using a two-site chemiluminescence immunoassay. Predictive Epo values in response to the degree of anemia were calculated by the equation: logEpo = (3.48 - 0.20) x Hb. According to the results, CDA anemia was present only in patients with active disease. These patients also had a significantly higher possibility of altered Epo levels than expected compared with patients with inactive disease (16/21 vs. 4/12, P < 0.05). It was also interesting that most of the patients with anomalous Epo concentrations presented with an elevated Epo value compared with that expected from the calculation (14/20). It seems that disturbed Epo concentrations are correlated with disease activity in children and adolescents with IBD. It is possible that failure of the bone marrow to respond to increased Epo levels leads to further incremental response. These in turn lead to the high Epo concentrations detected in most of the authors' patients. Impaired Epo production is another mechanism of CDA development and is the one mainly expressed in patients with low Epo values.     

CD11b-positive cells expression in rectal mucosa from ovalbumin sensitized and challenged rabbits

Rabbit MAC-1 receptor, homologue to human CD11b is present in macrophages. The aim of the study was to determine quantitative and distributive modifications of CD11b-positive cells that participate in immune response at rectal mucosa, in an animal model of mucosal immunity. New Zealand rabbits were divided into three groups. G1: control; G2: ovalbumin (OVA) sensitized; G3: OVA-senstitized and rectal challenged. Animals were subcutaneously sensitized twice with 70 microg OVA and 30 ml aluminium hydroxide in 2 ml saline solution. Rectal challenge was developed with a solution of 50 mg OVA in 5 ml saline solution. Sensitized groups (G2 and G3) showed a positive PCA (Passive Cutaneous Anaphylaxis) at 1/160 fold dilutions. In G3 we observed a patchy mucosal edema, lymphangiectasis and eosinophil leucocyte infiltration. Cells were counted as the number of cells per high power field. G1: 9.64 (SE 0.22); G2: 18.10 (SE 0.09) and G3: 23.60 (SE 0.29). (G2 vs G1 p < 0.001; G3 vs G1 p < 0.001; G3 vs G2 p < 0.001). We conclude that there is a close relationship between the food antigen OVA penetration (after challenge) and the increase of CD11b positive cells in rectal mucosa. This fact could be due to the cellular influx to the inflammatory site by the action of chemotactic factors released after challenge.     

An evaluation of two dental simulation systems: virtual reality versus contemporary non-computer-assisted

Contemporary dental simulation systems were developed to improve dental students' transition from the preclinical laboratory to the clinic. The purpose of this study was to compare the efficacy of a virtual reality computer-assisted simulation system (VR) with a contemporary non-computer-assisted simulation system (CS). The objectives were to determine whether there were differences between the two systems in the quality of dental students' preparations and the amount of faculty instruction time. Students who completed their first year of dental school and had no previous experience preparing teeth were group matched according to their performance in the first-year Dental Anatomy laboratory course and assigned to VR (n=15) or CS (n=13). In the summer, they spent two weeks (approximately 3 hrs/day) executing amalgam and crown preparations on typodont teeth. Short presentations describing the preparations were given to both groups; however, preparation criteria were available on the computer for the VR group, while the CS group received handouts. Both groups could request feedback from faculty, although VR also obtained input from the computer. A log was kept of all student-faculty (S-F) interactions. Analysis of the data indicated significant differences between groups for the following variables: mean number of S-F interactions was sixteen for the VR group versus forty-two for the CS group; and mean time of S-F interactions was 1.9+/-2 minutes versus 4.0+/-3 minutes (p<0.001) for VR and CS, respectively. Faculty spent 44.3 hours "interacting" with twenty-eight students, averaging 0.5 hours per VR student and 2.8 hours per CS student. Thus, CS students received five times more instructional time from faculty than did VR students. There were no statistical differences in the quality of the preparations. While further study is needed to assess virtual reality technology, this decreased faculty time in instruction could impact the dental curriculum.     

Immunosuppressive and anti-inflammatory effects of nicotine administered by patch in an animal model

To study the immunological effects of nicotine, there are several rodent models for chronic nicotine administration. These models include subcutaneously implanted miniosmotic pumps, nicotine-spiked drinking water, and self-administration via jugular cannulae. Administration of nicotine via these routes affects the immune system. Smokers frequently use nicotine patches to quit smoking, and the immunological effects of nicotine patches are largely unknown. To determine whether the nicotine patch affects the immune system, nicotine patches were affixed daily onto the backs of Lewis rats for 3 to 4 weeks. The patches efficiently raised the levels of nicotine and cotinine in serum and strongly inhibited the antibody-forming cell response of spleen cells to sheep red blood cells. The nicotine patch also suppressed the concanavalin A-induced T-cell proliferation and mobilization of intracellular Ca(2+) by spleen cells, as well as the fever response of animals to subcutaneous administration of turpentine. Moreover, immunosuppression was associated with chronic activation of protein tyrosine kinase and phospholipase C-gamma1 activities. Thus, in this animal model of nicotine administration, the nicotine patch efficiently raises the levels of nicotine and cotinine in serum and impairs both the immune and inflammatory responses.     

Epstein-Barr Virus-associated Smooth Muscle Tumor of the Basal Ganglia in an HIV+ Child: Case Report and Review of the Literature

We describe the clinicopathologic features of an Epstein-Barr virus (EBV)-associated smooth muscle tumor arising in the basal ganglia of a 10-year-old human immunodeficiency virus (HIV)-positive child. Only a few cases of intracranial smooth muscle tumors are reported in the literature and virtually all of these have been extra-axial, involving the dura or sinuses in HIV+ adults. Our case underscores the need to include an EBV-associated smooth muscle tumor in the differential diagnosis when evaluating intracranial mass lesions in immunodeficient children.Corresponding author, e-mail: