Enhancing the Silanization Reaction of the Silica-Silane System by Different Amines in Model and Practical Silica-Filled Natural Rubber Compounds.

Diphenyl guanidine (DPG) is an essential ingredient in silica-reinforced rubber compounds for low rolling resistance tires, as it not only acts as a secondary accelerator, but also as a catalyst for the silanization reaction. However, because of concern over the toxicity of DPG that liberates aniline during high-temperature processing, safe alternatives are required. The present work studies several amines as potential alternatives for DPG. Different amines (i.e., hexylamine, decylamine, octadecylamine, cyclohexylamine, dicyclohexylamine, and quinuclidine) are investigated in a model system, as well as in a practical rubber compound by taking the ones with DPG and without amine as references. The kinetics of the silanization reaction of the silica/silane mixtures are evaluated using model compounds. The mixtures with amines show up to 3.7 times higher rate constants of the primary silanization reaction compared to the compound without amine. Linear aliphatic amines promote the rate constant of the primary silanization reaction to a greater extent compared to amines with a cyclic structure. The amines with short-alkyl chains that provide better accessibility towards the silica surface, enhance the primary silanization reaction more than the ones with long-alkyl chains. The different amines have no significant influence on the rate constant of the secondary silanization reaction. The amine types that give a higher primary silanization reaction rate constant show a lower flocculation rate in the practical compounds. For the systems with a bit lower primary silanization reaction rate, but higher extent of shielding or physical adsorption that still promotes higher interfacial compatibility between the elastomer and the filler surface, the rubber compounds show a lower Payne effect which would indicate lower filler-filler interaction. However, the flocculation rate constant remained high.

[Therapeutic effects of venlafaxine extended release for patients with depressive and anxiety disorders in the German outpatient setting - results of 2 observational studies including 8500 patients]. / Klinische Effekte von retardiertem Venlafaxin (Trevilor retard) bei Patienten mit Depression und Angsterkrankungen in der ambulanten Behandlungspraxis in Deutschland - Ergebnisse von zwei Anwendungsbeobachtungen mit 8500 Patienten.

The therapeutic effects of venlafaxine extended release have been investigated by two prospective observational studies including 8506 patients in the outpatient setting of office based general practitioners and specialists. The efficacy has been documented by the Clinical Global Impression (CGI) scale and by the Hamilton depression (HAMD-21) scale. The tolerability has been assessed by the documentation of adverse events. About (2/3) of the patients were treated because of depression and about (1/3) mainly because of anxiety disorder. The patients of specialists did receive higher dosages and were more severely affected. The response rate on the CGI scale was 87.4 for the patients of general practitioners and 74.2 % for the patients of specialists. The results of the HAMD-21 scale, which has been used by specialists, showed a response rate of 71.8 and a remission rate of 56.3 %. These positive effects could be demonstrated even for the more severely and chronically affected patients. The incidence of adverse events was low in both studies and comparable to the tolerability profile of randomized studies. Importantly, the good tolerability profile was similar even for patients with concomitant cardiovascular disease. In conclusion, these results confirm the efficacy and good tolerability of venlafaxine extended release in the outpatient setting in Germany.

Non-pharmacological treatment of psychiatrists in addition to the prescribing of an antidepressant drug.

BACKGROUND: Guidelines for the treatment of depression regularly emphasize that pharmacotherapy of depression should be accompanied by supportive counseling and other psychotherapeutic interventions. It is unknown which role psychiatrists in routine care give to such verbal therapies. METHODS: In a drug utilization study of venlafaxine, psychiatrists in private practice and in hospitals were asked to tell what non-pharmacological therapies they saw as an important part of the treatment of the present depressive episode. Additionally patient characteristics, treatment variables, setting characteristics and physician characteristics were assessed. RESULTS: Psychiatrists reported some kind of verbal therapies in 19.0% of outpatients and 36.8% of inpatients. Verbal therapies were reported more often for younger patients, who got more double diagnoses and were more severely ill. Patients with verbal therapies got more psychotropic medication. In the inpatient setting verbal therapies were related to generally more treatment overall and a higher rate of treatment response. In both treatment settings verbal therapies were related to lower rates of discontinuation of the antidepressant. CONCLUSION: Verbal interactions are part of any patient-physician encounter and should be theory guided as part of the therapeutic process in the treatment of depressive disorders. Under this assumption the rate of patients for which psychiatrists reported some kind of verbal therapy as explicit part of their treatment could be higher. More research is needed on patient guidance, counseling and supportive psychotherapy in psychiatry.

Dosage finding and outcome of venlafaxine treatment in psychiatric outpatients and inpatients: results of a drug utilization observation study.

BACKGROUND: Venlafaxine is an antidepressive drug with the special characteristic of inhibiting both synaptic serotonin and norepinephrine reuptake. This double action is dosage dependent, with the relatively weaker inhibition of norepinephrine becoming clinically relevant only at higher dosages. This allows treatment to be tailored towards the needs of individual patients through differential dosing. It is unknown, however, how physicians use this unique feature in prescribing venlafaxine in routine treatment. METHOD: Data from a drug utilization observation (DUO) study, including 6706 patients, are used to investigate which patient and setting variables predict dosage of venlafaxine as prescribed by psychiatrists in inpatient and outpatient settings. Treatment outcome and adverse drug reactions (ADR) were analyzed for different dosage groups. RESULTS: Treatment setting is the most important factor in predicting high (> 75 mg/day) or low (up to 75 mg/day) dosage of venlafaxine, with inpatients receiving higher dosages. Severity of illness and a history of previous treatment with major antidepressives are also related to higher dosages. Although the total rate of ADR did not increase with increased dosage, the profile of drug reactions changed. Response to therapy was better in cases of non-chronic, major depression with no treatment history of antidepressives. Additionally, increased dosage increased the likelihood of response in outpatients. In both settings, very high dosages predicted better response to venlafaxine among severely ill patients. CONCLUSION: Venlafaxine at a dosage of 75 mg/day is sufficient for the majority of cases. In extremely ill patients, higher dosages are associated with additional benefits. Therefore, a stepwise dosage regimen is suggested, with an increase of dosage to upper limits in cases of non-response before discontinuation of treatment with venlafaxine.

Long-Term Production of Ergot Peptides by Immobilized Claviceps purpurea in Semicontinuous and Continuous Culture.

The semicontinuous and continuous production of pharmaceutically useful ergot peptides with immobilized Claviceps purpurea could be demonstrated. A key aspect was the presence of high concentrations of CaCl(2) (96.9 mM) to give marked prolongation of the productive phase, and cultivation in a bubble column reactor became possible. Restriction of the phosphate supply avoided an otherwise problematic massive increase of outgrowing hyphae.