[Original preparations versus generics--latanoprost: how similar is different?]. / Originalpräparat versus Generika--Latanoprost : Wie gleich ist unterschiedlich?

BACKGROUND: To test the interchangeability of the commercially available (in Germany) latanoprost drugs and their generics respectively, the concentration of the active substance was tested. Guidelines of the European Medicines Agency postulate a sufficient bioequivalence, if the range of the agent is within 80-125% of the original drug. METHODS: All compounds of latanoprost were procured registered. The concentration of latanoprost and benzalkoniumchloride was measured by high-performance liquid chromatography (HPLC) in a validated reference labroratory for 23 generics. In addition, the mean volume of drops and the pH of the formulation were measured. The packaging label and the readability of the enclosed information leaflet were checked. RESULTS: All products contained less than 50 µg/ml latanoprost. The deviating reduction of the active substance (mean: - 7.39%, ± 2.8%) was accompanied by fluctions of the eyedrops' mass (mean: 0.03 g, ± 0.002 g). The concentration of benzalkonium chloride was mostly increased (median: 5.45%, min: - 2.5%, max: 11.5%). The pH of the original drug and the generics (median 6.78, min: 6.62, max: 6.81) was similar to the original drug, but was significantly different from an unpreserved formulation (pH 7.18). Due to type size, the packaging leaflet was illegible for humans with impaired vision. CONCLUSIONS: Before prescribing generics in ophthalmology, different factors have to be considered, which might influence the amount of IOP lowering in effect. In the absence of healthcare research it is still unclear, how different bottle forms of eyedrops--such as appearance (e.g. Cyrillic characters) or pressure point (administration)--reduce the adherence of glaucoma patients.

Deviance-related electrophysiological activity in mice: is there mismatch negativity in mice?

OBJECTIVE: Mismatch negativity (MMN) is an auditory event-related potential (ERP) that provides an index of auditory sensory memory and has become an important tool to investigate auditory sensory memory in cognitive neuroscience and disorders such as schizophrenia and dyslexia. The development of a mouse model of human MMN would permit to investigate the molecular biology of normal and dysfunctional MMN generation. However, the presence of MMN-like electrophysiological activity in mice has not been demonstrated. METHODS: Deviance-related ERPs were recorded in awake mice using 3 frequency deviance paradigms and one duration deviance paradigm. These paradigms were modelled after paradigms used in human studies to characterize MMN. RESULTS: Significant deviance-related activity was observed in all paradigms. However, in all frequency deviance paradigms this activity manifested as an enhancement of similar activity to the standard due to differences in stimulation rate between deviant and standard stimuli rather than qualitatively different MMN-like activity. In the duration deviance paradigm negative deflections were observed that showed characteristics typical of human MMN. CONCLUSIONS: MMN-like activity can be observed in mice in duration deviance paradigms. In frequency deviance paradigms effects of different stimulation rates of deviant and standard stimuli seem to be the main determinants of deviance-related activity. SIGNIFICANCE: Investigations of MMN-like ERPs in mice may permit to investigate the molecular basis for normal and abnormal MMN generation in neuropsychiatric disorders and dyslexia.

Use of hematopoietic growth factors in elderly patients receiving cytotoxic chemotherapy.

Myelosuppression is a common side effect in elderly patients undergoing chemotherapy. Neutropenia and anemia cause considerable morbidity, may increase mortality, and can result in a worse outcome of treatment in elderly patients compared to younger patients with comparable type and stage of disease. The availability and proven efficacy of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) have had a considerable impact on supportive care in cancer patients: Several randomized trials have demonstrated a reduction of neutropenia and the frequency of severe infections in elderly patients treated with G-CSF following myelotoxic chemotherapy compared with patients without growth factor support. Both for G-CSF and for recombinant human erythropoietin (rHu-EPO) several studies have demonstrated the safety and effectiveness of these molecules in elderly patients with regard to increasing hemoglobin concentrations, improving quality of life (rHu-EPO), and neutrophil recovery. Although a positive effect of the use of growth factors on overall survival in elderly cancer patients is not yet proven, a reduction of chemotherapy-induced side effects could clearly be shown. The National Comprehensive Cancer Network (NCCN) of cancer centers has recommended that all patients aged 70 years and older treated with CHOP or cytotoxic chemotherapy of comparable intensity should receive prophylactic G-CSF administration, and that the hemoglobin concentration be maintained at >or=12 g/dl in elderly patients undergoing chemotherapy.

A stereotaxic x-ray map of the hypothalamus of the marmoset monkey Callithrix jacchus.

Precise hypothalamic surgery in the marmoset monkey Callithrix jacchus cannot be performed by means of the Horsley-Clarke stereotaxic procedure. Thus, a simple stereotaxic X-ray technique was developed. Technical requirements are a stereotaxic frame for small animals and a dental X-ray source. A sagittal map shows hypothalamic structures in relation to surrounding bony landmarks. Corresponding coronal plates allow target determination in that plane. Intracerebral coordinates based on the position of the optic chiasma can be transformed into individual Horsley-Clarke coordinates. The error of the atlas is estimated as +/- 0.25 mm anteroposteriorly, +/- 0.1 mm coronally, and +/- 0.5 mm vertically.

Differential hypothalamic self-stimulation behaviour in Roman high-avoidance and low-avoidance rats.

Monopolar electrodes were implanted bilaterally and symmetrically into a small well defined region of the posterior lateral hypothalamus in 11 rats of the selected strains Roman high-avoidance (RHA/Verh, 6 animals) and Roman low-avoidance (RLA/Verh, 5 animals). Intracranial electrical stimulation (ICS) was used to study possible strain difference with respect to self-stimulation behaviour. Using a shuttle-box, the experimental set-up allowed measurements of the animal's preference, aversion, neutrality or ambivalence towards the stimulus. For both rat strains 10 electrode sites were tested with identical stimulation currents (100-600 microA in increments of 100 microA). Significant differences between the selected strains were found for preference (self-stimulation) and aversion: RLA/Verh-rats showed self-stimulation at lower stimulation currents than RHA/Verh-rats. At higher currents, both strains showed similar self-stimulation performance. RLA/Verh-rats escaped more often from ICS yielding self-stimulation at five of the six current levels. It is concluded that, in comparison with the RHA strain, RLA/Verh-rats are more sensitive to aversive effect of lateral hypothalamic stimulation. This seems to be associated with an increased sensitivity to the rewarding effects of such stimulation.

Aggression and flight behaviour of the marmoset monkey Callithrix jacchus: an ethogram for brain stimulation studies.

The aggressive and flight behaviour of the common marmoset monkey (Callithrix jacchus) is described and split into behavioural units, allowing analysis of agonistic behaviour evoked by electrical stimulation of the hypothalamus. The social context of the described units is also considered. C. jacchus shows clearly recognizable behavioural patterns. Free-born animals are very timid and show typical flight reactions. Within aggressive behaviour, two types of aggression can be distinguished: very violent attacks causing severe injuries, often accompanied by particular threat displays and observed during dominance and territorial encounters, and, on the other hand, relatively harmless short attacks, together with a noisy vocalization, for defensive purposes or keeping group members at a distance.

Threat, attack and flight elicited by electrical stimulation of the ventromedial hypothalamus of the marmoset monkey Callithrix jacchus.

In order to elucidate whether relatively primitive primates show a similar topological organization of substrates mediating defense and flight within the ventromedial hypothalamus as has been found in other mammals, 15 marmosets (Callithrix jacchus) were chronically implanted with a total of 57 electrodes for electrical stimulation. Experiments took place in a familiar environment and under systematically altered conditions. All anatomical sites yielding vocal threat and short attacks were found to be situated in the n. ventromedialis. Flight was elicited from a region immediately lateral to this nucleus and from sites in the posterior hypothalamus. Thus, it appears that the topological organization of defense and flight behavior in cat, oppossum and marmoset are essentially similar.