R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long–Evans rats. As Long–Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long–Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine''s effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans.     

Genetic heterogeneity of "normal" human erythrocyte glucose-6-phosphate dehydrogenase: an isoelectrophoretic polymorphism.

Quantitative determination of glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate: NADP+ 1-oxidoreductase, EC 1.1.1.49) activity was carried out in 214 male Nigerian children of 84 mothers with known Gd genotype. The relative intrasibship difference in G6PD activity (normalized to the lowest value within the sibship) was below 0.18 in all cases but one when the children were known to have the same Gd+ allele (identical by descent); whereas it was higher than 0.18 in 18 out of 33 sibships in which children might have had either of the two maternal (electrophoretically identical) Gd+ alleles. G6PD from 10 (8 G6PD B and 2 G6PD A) children belonging to four of the sibships possessing high quantitative variation in G6PD activity was partially purified and extensively characterized. The 8 G6PD type B samples fell unambiguously into two classes on the basis of Km values for glucose 6-phosphate (determined at variuos pH values), and KCl gradient elution from DEAE-Sephadex columns. The two types of G6PD B were resolved from an artificial mixture on a DEAE-Sephacel column. The two G6PD type A samples were also different from each other by the same criteria. We conclude that "normal" G6PD is genetically heterogeneous and that the structural Gd alleles concerned are all polymorphic in the Nigerian population. In this instance, a human enzyme polymorphism, not associated with enzyme deficiency, is revealed by an approach other than electrophoresis.     

Salmonella enterica Serovar Enteritidis,England and Wales, 1945–2011

In England and Wales, the emergence of Salmonella enterica serovar Enteritidis resulted in the largest and most persistent epidemic of foodborne infection attributable to a single subtype of any pathogen since systematic national microbiological surveillance was established. We reviewed 67 years of surveillance data to examine the features, underlying causes, and overall effects of S. enterica ser. Enteritidis. The epidemic was associated with the consumption of contaminated chicken meat and eggs, and a decline in the number of infections began after the adoption of vaccination and other measures in production and distribution of chicken meat and eggs. We estimate that >525,000 persons became ill during the course of the epidemic, which caused a total of 6,750,000 days of illness, 27,000 hospitalizations, and 2,000 deaths. Measures undertaken to control the epidemic have resulted in a major reduction in foodborne disease in England and Wales.     

Pattern of dental extraction in children in a Nigerian tertiary hospital

Changes that occurred in the pattern of tooth extraction in the last 13 years among a population of children in Nigerian were studied. The result of this study was then compared to that of a past study done in the same institution 13 years earlier. Information on age, gender, and indication of tooth extraction was collected prospectively from 379 consecutive patients who visited the outpatient Pediatric Dental Clinic for the first time during the year 2002. Results showed tooth extraction due to caries decreased, while there was an increase in tooth extraction from an apparent increase in orthodontic treatment needs. Acute necrotizing ulcerative gingivitis (ANUG), a significant cause of tooth loss in the last decade, decreased significantly. The pattern of deciduous tooth loss also changed as more anterior teeth were lost for orthodontic reasons in this present study. The pattern of tooth loss in the permanent dentition remains very similar to that of the past study, though more premolars were lost in the present study. There appears to be an increasing need for tooth extractions in orthodontic treatment for this population of children. The focus of planned dental health care provisions, treatment policies, and training emphasis in child dental care may need to shift to addressing orthodontic needs.     

HIV seroprevalence in emergency department patients: Lagos University Teaching Hospital, Lagos, 1999

The emergency department patients represent a cross-section of the entire population and values of HIV seroprevalence in them have been used to assess the general trends of HIV surveillance in other countries. The objectives of this study is to determine 1. Whether seroprevalence of HIV antibodies in patients attending emergency departments could serve as a marker of prevalence of HIV antibody in the general population. 2. The degree of clinical suspicion or knowledge of the medical personnel to the status o the HIV seropositive patients is also evaluated. A total of 312 emergency department patients of Lagos University Teaching Hospital (LUTH) had their blood samples screened for antibodies against Human Immunodeficiency Virus (HIV) types I and II by ELISA based techniques: Immunocomb II HIV I & II Bispot Kits. Repeatedly reactive samples were confirmed by another ELISA based technique using Immunocomb I & II Combfirm kits. The attending medical doctor was asked whether there was any suspicion or knowledge that the patient being attended to, was HIV seropositive. The seroprevalence of HIV antibodies was 5.77% with no significant difference in sex incidence. The age groups 20-29 and 30-39 years were most affected. The seropositive nature of affected patients was unsuspected by medical personnel in 55.56% of the HIV antibodies seropositive patients. The Federal Ministry of Health in 2000, estimated the National prevalence rate of HIV to have been 5.4% in 1998. This figure is comparable to that obtained in this study and revalidates the fact that emergency department patients may be used for disease surveillance in the population. The seropositive status of majority of the HIV positive patients was unsuspected by the attending medical personnel. Thus, strict adherence to universal safety precautions is essential for all medical personnel. Post exposure prophylaxis should be made readily accessible to all medical personnel.     

Diagnosis of iron deficiency anaemia among Nigerian pregnant women by serum iron/T.I.B.C. determination.

Fifty-five patients have been investigated for anaemia in pregnancy. Using the serum iron/T.I.B.C. ratio as a diagnostic index it has been found that iron deficiency exists in 60% of our expectant mothers with mild anaemia. This type of anaemia was more common in multiparous women and more frequent in the first and second trimesters of pregnancy, There is, therefore, a strong indication for the routine administration of iron supplements to our women during pregnancy and the puerperium.     

Involvement of histamine in naloxone-resistant and naloxone-sensitive models of swim stress-induced antinociception in the mouse

The antinociceptive activity of histamine in male mice has been demonstrated using chemical and thermal noxious stimuli and its involvement in naloxone-sensitive and naloxone-insensitive models of stress-induced antinociception investigated. In the abdominal constriction test, histamine and dimaprit but not histidine, induced antinociception. Compound 48/80 and H1 antagonists (diphenhydramine, mepyramine and promethazine) and large doses of H2 antagonists (cimetidine and zolantidine) produced antinociception in this test. Antinociception induced by histamine was refractory to mepyramine, metiamide and naloxone. Histamine and non-antinociceptive doses of its antagonists had no influence on the naloxone-resistant warm water swim stress-induced antinociception. In the hot-plate test, histamine agonists, except the H3 agonist (R) alpha-methyl histamine (alpha-MeHA), were antinociceptive but all these agents augmented the naloxone-sensitive room temperature swim stress-induced antinociception, after either intraperitoneal or intraventricular injection. The antinociceptive action of dimaprit was not antagonized by zolantidine which, like other histamine antagonists excluding metiamide, also produced antinociception and enhanced room temperature swim stress-induced antinociception. These findings suggest that histamine is involved in pathways mediating antinociception in the mouse and that such pathways are activated in a naloxone-sensitive model of stress-induced antinociception but not in a naloxone-insensitive model.     

Structure-Activity Relationships at the Monoamine Transporters for a Novel Series of Modafinil (2-[(diphenylmethyl)sulfinyl]acetamide) Analogues

A series of modafinil (1) analogues was synthesized wherein 1) para-halo-substitutents were added to the aryl rings, 2) the sulfoxide function was removed, and 3) the primary amide group was replaced with secondary and tertiary amides and amines to investigate the effects of these chemical modifications on DAT, SERT and NET binding. In addition, the locomotor-stimulant effects in mice of (±)-modafinil (1), its R- and S-enantiomers and its para-chloro sulfinylacetamide analogue (5c) were compared to those of cocaine.