In vitro/in vivo correlation of prolonged release dosage forms containing diltiazem HCl

Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and t_d of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and t_d between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t_1/2 (7.12 h), while apparent t_1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for C_max and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p <0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the ‘Levy's plot’ (per cent released versus per cent absorbed) approach and provided further support for the correlation found.     

Muscarinic modulation of endogenous noradrenaline release from adrenergic terminals in the guinea-pig colon

1 The present study examined the role of muscarinic receptors in the modulation of noradrenaline (NA) release in the guinea-pig isolated distal colon. The spontaneous endogenous NA overflow assayed by HPLC-ED was taken as an index of NA release from enteric noradrenergic nerve terminals. 2 Physostigmine (10 μm ) significantly enhanced spontaneous endogenous NA overflow. Hyoscine (muscarinic antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M₁-selective antagonists), and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116, M₂-selective antagonist) inhibited NA overflow in a concentration dependent manner, with the following EC₅₀ values: 131.74 (18.19–953.96), 101.62 (58.83–175.60), 150 (60–330), 30 (5–170) nm , respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M₁- and M₃- selective antagonist) had no significant effect up to 100 μm . 3 The muscarinic agonist oxotremorine inhibited NA overflow in a concentration dependent manner, with an EC₅₀ value of 0.67 (0.30–1.51) μm . The response to oxotremorine was inhibited by muscarinic antagonists with the following order of potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine > 4-DAMP >> AF-DX 116. 4 In the presence of 3 μm tetrodotoxin (TTX), the effect of oxotremorine and 4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF-DX 116, instead of inhibiting, significantly enhanced NA overflow. 5 The present results indicate that, in the guinea-pig colon, endogenous acetylcholine sustains spontaneous NA release by activating muscarinic receptors possibly located on interneurones. In addition, inhibitory muscarinic receptors may exist on adrenergic terminals.     

Elements of psychological support in nursing care

The paper presents the results of a pilot study which involved 50 nurses from several departments of internal medicine of The State Clinical Hospital of the Collegium Medicum, Jagiellonian University in Cracow. The results are based on the Statement Response Questionnaire. They show that the most common responses of the nurses in the face of anxiety expressed by patients are cheering up the patient, collecting information about the symptom, and offering explanation of the symptom. The least common responses included expressing one's own positive emotions and showing empathy towards the patient.     

An analysis of paramagnetic centers in irradiated dentin using electron spin resonance

Summary The ESR spectra produced in irradiated dentin have been studied over a range of incident radiation energies from 50 kVp to 25 MVp. The behavior of the dentin ESR signal strength is similar to that of enamel as a function of the energy of the incident radiation. The magnitude of the dentin ESR signals are, however, up to 10 times smaller than the signals of dental enamel for a given radiation energy. The possible contributions of radiation interaction coefficients, chemical structure, and crystallite size to the differences in ESR spectra are discussed.     

Extracapsular cataract surgery and intraocular lens implantation in glaucomatous eyes that had a filtering bleb operation

We studied 112 eyes of 80 glaucomatous patients who had filtering operations and also developed cataracts. Extracapsular cataract extraction (ECCE) was performed in all eyes. One hundred four (104) eyes had posterior chamber intraocular lenses (IOLs) implanted and eight had ECCE without IOLs; the latter were excluded from this clinical investigation. We evaluated intraocular pressure (IOP) and visual acuity and examined the visual fields during a follow-up period of eight months. We compared these results with the preoperative measurements. This study demonstrates that ECCE and posterior chamber IOL implantation is the optimal solution for glaucomatous eyes that have had a filtering bleb operation to obtain a good functional result and IOP stabilization.     

BUILDING COMMUNITY: Developing Skills for Interprofessional Health Professions Education and Relationship-Centered Care

In 1995, the National League for Nursing commissioned a Panel on Interdisciplinary/Transdisciplinary Education. The focus of the Panel's work was to examine educational issues that transcend the health professions and to make recommendations for future implementation of an interdisciplinary approach to addressing them. This article is being simultaneously published by several professional journals. The goal is to seek as much feedback as possible.     

Transitional progressive multiple sclerosis: MRI and MTI findings

Transitional progressive multiple sclerosis (MS) is quite an unusual form of presentation and course of the disease. A case with this progressive form is presented and brain MRI and MTI findings are discussed in relation to the possible insight they may provide for understanding the mechanisms that determine progressive disability in MS.     

Minorities and AIDS

A common misconception is held among many ethnic minoritiesin San Francisco that AIDS is exclusively a ‘gay whitemale disease’. This myth is false, but dangerous. To assistethnic minorities in understanding their risks for AIDS, successfuleducational programs for these populations must recognize thediversity within these communities, including their differingcultures, languages and religious backgrounds. San Franciscohas adopted a model that utilizes well-established and well-respectedcommunity-based organizations to provide the education and riskreduction programs. Utilizing these organizations allows foreducation of diverse populations that is culturally and linguisticallyrelevant, thus allowing San Francisco an opportunity to preventthe national minority AIDS statistics from occurring withinits boundaries.     

Preconditions for and consequences of self-determination: the psychiatric patient's point of view

In the context of an interview study concerned with self-determination in psychiatric patients, this paper describes the preconditions for and consequences of self-determination from the point of view of psychiatric patients themselves. The data were collected in semi-structured interviews with long-term psychiatric patients ( n =72) and analysed using the method of content analysis. Responses on the preconditions for self-determination were grouped into three categories: firstly, there were those who said that reference to self-determination in the case of psychiatric patients is nonsense; secondly, there were those who said that self-determination requires no preconditions; and thirdly, there were those who said that there are certain preconditions, such as the ability to think and make decisions, activity, obedience, and illness. Both positive and negative consequences were identified in situations where self-determination is maintained, but only negative consequences in situations where self-determination is lost. On the basis of these tentative results, self-determination seemed to be relevant in psychiatric nursing. We are continuing to develop and test an instrument for the evaluation of the opportunity for self-determination in clinical practice.     

Neurotensin injected into the nucleus accumbens blocks the psychostimulant effects of cocaine but does not attenuate cocaine self-administration in the rat

The neuropeptide neurotensin (NT) has been shown to modulate mesolimbic dopaminergic activity. Neurotensin injected into the VTA produces motor stimulation and release of dopamine in the nucleus accumbens. In contrast, when neurotensin is administered into the nucleus accumbens, it produces neuroleptic-like effects such as attenuation of the locomotor activity elicited by psychostimulants. In the present study, the hypothesis that neurotensin injected into the nucleus accumbens might modulate the psychostimulant and reinforcing actions of cocaine was tested. In experiment one, rats were trained to self-administer cocaine intravenously on an FR5 schedule of reinforcement. Following the establishment of baseline responding, rats were implanted with bilateral cannulae in the nucleus accumbens. One week later, rats were injected into the nucleus accumbens with various doses of neurotensin (4.2, 8.4 and 16.7 μg, total doses bilaterally) immediately prior to the self-administration session. No significant effects were found with any of the doses of neurotensin tested on the self-administration of cocaine. However, in experiment 2, neurotensin at doses of 4.2 and 16.7 μg injected into the nucleus accumbens significantly reduced the locomotor activation induced by an acute injection of cocaine (15 mg/kg i.p.) and a dose of 16.7 μg attenuated the locomotor activation induced by amphetamine (0.75 mg/kg i.p.). Thus, neurotensin in the nucleus accumbens appears to specifically modulate the acute locomotor activating properties of cocaine but not cocaine self-administration. Different mechanisms by which NT interacts with dopamine in the nucleus accumbens may provide a means of selectively altering psychostimulant motor actions without affecting psychostimulant reinforcement.