A Comparison of the Physicochemical and Biological Properties of Mirtazapine and Mianserin

Although the chemical structures of the antidepressants mirtazapine and mianserin are closely related there are considerable differences in their biological properties. To find an explanation of this, various physicochemical properties of mirtazapine and mianserin were measured or calculated. Isosteric replacement of CH in mianserin by N in mirtazapine has profound effects on physicochemical properties. The charge distributions as indicated by NMR and calculated by semi-empirical quantum mechanics differ, not only for the changed aromatic A-ring (as expected), but also in other regions of the molecule. The N5 atom in particular, which is conjugated to the changed aromatic ring, is less negatively charged in mirtazapine than in mianserin. Consequently the oxidation potential of mirtazapine is significantly higher than that of mianserin. Another result of this difference in charge distribution is that the (calculated) dipole-moment vectors of the compounds are oriented roughly perpendicular to each other. The dipole moment of mirtazapine is, moreover, three times larger than that of mianserin; mirtazapine is, therefore, more polar than mianserin and this is reflected in a lower retention index. Finally, the basicity of mirtazapine, expressed as the pK_a value, is slightly but significantly lower than that of mianserin. The observed differences between the physicochemical properties of mirtazapine and mianserin result in different interactions of these two antidepressants with macromolecules, such as receptors, transporters and metabolizing enzymes; this might explain the differences observed in pharmacological activity and metabolic and kinetic behaviour, that is, the reduced affinity for the α₁-adrenoceptor and negligible noradrenaline reuptake of mirtazapine compared with mianserin.     

Change Processes in Psychotherapy

Efforts to understand the processes of change in psychotherapy have typically been based on either clinicians' experiences or on empirical studies somewhat removed from the day-to-day work and concerns of psychotherapists. This paper reviews selected examples of insights and issues derived from each of these sources. It is suggested that our understanding of change processes in psychotherapy will be enhanced by the growing convergence between the two approaches.     

Unsweetened ice popsicles impart a positive feeling and reduce self‐mutilation after paediatric dental treatment with local anaesthesia

International Journal of Paediatric Dentistry 2010; 20: 382–388 Aim. The purpose of the current study was to assess whether an unsweetened ice‐popsicle imparts a positive feeling to children after dental treatment in which local anaesthesia is administered, and whether it reduces the tendency of children to self‐mutilate (bite the lip, cheek or tongue) after the administration of local anaesthesia. Design. Crossover study of 31 children aged 4–11 years old who needed similar dental treatments on both sides of the mandible or maxilla under local anaesthesia. At the end of each appointment the child received a toy or an ice‐popsicle especially made for this study. Patients and parents answered a questionnaire regarding the children’s behaviour and feeling immediately after the treatment, and 10 and 30 min after receiving the ice‐popsicle or toy. Results. Children who received ice‐popsicles after dental treatment under local anaesthesia felt less discomfort and suffered less soft tissue trauma than they did when they received a toy. Reduction in soft tissue trauma was evident 10 min after receiving the ice‐popsicles. Conclusion. Licking of an ice‐popsicle after dental treatment with local anaesthesia reduces the feeling of discomfort and the biting of soft tissue and self‐ mutilation.     

The effects of routine oxytocic administration in the management of the third stage of labour: an overview of the evidence from controlled trials

Summary. Recent claims that routine active management of the third stage of labour increases rather than decreases maternal and neonatal morbidity have prompted us to conduct a systematic review of the relevant controlled trials. In this paper we have analysed data derived from a total of nine published reports of controlled trials in which an oxytocic drug was compared with either a placebo or no routine prophylactic. Oxytocic drugs used routinely appear to reduce the risk of postpartum haemorrhage by about 40% (typical odds ratio 0·57, 95% confidence interval 0·44–0·73) implying that for every 22 women given such an oxytocic, one postpartum haemorrhage could be prevented. The available data are insufficient to assess the possible effects of this policy on the incidence of retained placenta, hypertension and other possible adverse effects.     

Antibody responses to a 33 kDa cysteine protease of Trypanosoma congolense: relationship to 'trypanotolerance' in cattle

A cysteine protease of Trypanosoma congolense (congopain) elicited IgG1 antibodies in those cattle which exhibited a degree of resistance to disease during experimental infections (Authié et al. 1992, 1993). The aim of the present study was to investigate further the association between anti-congopain antibodies and resistance to trypanosomiasis, and to provide a lead into the mechanisms responsible for the differential responses to congopain in cattle. Isotype characteristics and kinetics of the antibody response to congopain were studied in three N'Dama (trypanoresistant) and three Boran (susceptible) cattle during primary infection with T. congolense ILNat 3.1. In both groups an IgM response to congopain was elicited, thus demonstrating that congopain is antigenic in both types of cattle. Most of the IgM appeared to be incorporated into immune complexes. IgG was detected as free antibody; IgG1 but not IgG2 was detected. All three N'Dama, but none of the three Boran cattle, mounted a significant IgG response to congopain. Sera from 70 primary-infected cattle belonging to five breeds of differing susceptibility were tested for their reactivity to congopain. High levels of IgG to congopain were observed in the two trypanotolerant breeds, whereas the three susceptible breeds had lower levels of these antibodies. Crosses between N'Dama and Boran cattle, which exhibit an intermediate susceptibility, had intermediate levels of antibodies. Thus, the results from experimental infections confirmed our initial observations. However, under natural tsetse challenge, repeated infections and trypanocidal treatments in Zebu cattle stimulated as high anti-congopain antibody levels as in non-treated trypanotolerant taurine cattle.     

Microbiota of gingivitis in man

ABSTRACT – A Study on the predominant cultivable microorganisms inhabiting gingival crevices affected with a chronic gingivitis was carried out using the roll tube culture technique. Samples were obtained from nine individuals 25–42 years of age. Gram-positive rods made up 26.1% of the isolates and included mainly Actinomyces naeslundii, Actinomyces israelii , and Actinomyces viscosus. Streptococcus mitis and Streptococcus sanguis together made up 26.8% of the cultivable organisms. Feptostreptococcus averaged 3.0% of the organisms recovered. Gram-negative anaerobic rods constituted 25.0% of the total isolates with Fusobacterium nucleatum, Bacteroides melaninogenicus ss. intermedius, Bacteroides ochraceus , other Bacteroides species, Selenomonas sputigena , and Campylobacter sputorum as the most predominant isolates. Haemophilus parainfiuenzae averaged about 14% and Veillonella species 4.3% of the cultivable microflora. The data presented indicate that the subgingival microflora of a chronic gingivitis differs from those of healthy periodontium and advanced adult and juvenile periodontitis. This might suggest that different infectious processes may be operative in various clinical entities of periodontal disease.     

Autocannibalism: The Etiology of Nerve-Resection Anemia

1. The finding of Hollán that severe anemia follows nerve resection in ratshas been confirmed.

2. By the use of total-body labeling with radioiron, it has been demonstratedthat this anemia is due to blood loss.

3. The blood lost by the nerve-sectioned rat is found in the stools, but autopsy reveals no source of gastrointestinal bleeding.

4. Anemia occurs only in animals with excoriation of the denervated foot.Anemia may be precipitated by withdrawing food for 48 hours. Hollán hasfound that amputation of the denervated limb prevents onset of the anemia.

5. It is concluded that nerve-resection anemia in the rat is due to autocannibalism of the denervated foot.

Submitted on June 1, 1959 Accepted on August 19, 1959