In vitro dissolution profiles of enteric-coated microsphere/microtablet pancreatin preparations at different pH values

Objectives : Enteric-coated microsphere/microtablet pancreatin should stay intact in the stomach and dissolve promptly on entering the duodenum. Post-prandial intraluminal pH in the distal duodenum is 5.75 and is lower in exocrine pancreatic insufficiency. The aim of the study was to measure in vitro dissolution times in buffer solutions with pH 4.0–6.0 for five currently available enteric-coated microsphere/microtablet pancreatin preparations.
Methods : The following preparations were tested: Creon, Creon Forte, Pancrease, Pancrease HL and Panzytrat. Two capsules were placed in the buffer solution at 37 °C in a USP dissolution testing apparatus. Buffer solutions with pH between 4.0 and 6.0 were used. Solutions were stirred at 125 r.p.m. and the rate of dissolution was monitored by taking 2-mL samples at regular intervals and measuring extinction at 280 nm. Measurements were repeated six times.
Results : All preparations failed to dissolve at pH 4.0. At pH 5.0 Pancrease HL showed 43% dissolution within 30 min, all other preparations 15% or less. Panzytrat and Pancrease HL showed more than 50% dissolution within 30 min at pH 5.2. Panzytrat, Pancrease HL and Creon Forte had more than 90% dissolution within 30 min at pH 5.6, and all preparations more than 90% dissolution within 30 min at pH 5.8 and higher.
Conclusions : For the treatment of exocrine panceatic insufficiency conventional strength enteric-coated microsphere/microtablet pancreatin preparations do not have an optimal dissolution profile. The newer, high lipase preparations such as Pancrease HL perform better, although still not optimally, at pH 5.4 and lower.     

Isolation of cDNAs encoding immunogenic regions of gp330, the autoantigen involved in Heymann nephritis

Active Heymann nephritis is an organ-specific autoimmune disease of the rat kidney, characterized by the formation of immune complexes located subepithelially in the glomerulus. The T cell-mediated humoral immune response is directed to gp330, a large renal epithelial glycoprotein which is expressed both in the proximal tubule and on glomerular podocytes. In this study polyclonal rabbit antibodies raised against affinity-purified rat gp330 were used to screen a λ-gt11 expression library of the rat kidney. One cDNA clone that was recognized by the antibodies coded for a 2.7-kb protein that is not described in the sequence database of GenBank/EMBL. Two other groups of cDNA clones were identified that displayed similarity with several members of the low-density lipoprotein (LDL)-receptor gene family to which gp330 belongs. By comparison with the gp330-cDNA sequence, these two clones could be mapped to two remote areas on the extracellular domain of gp330. The antigenicity of these two areas is in accordance with their location in highly hydrophilic regions on the extracellular domain of gp330. The cDNA clones described in this study may represent two main immunodominant regions on rat gp330.     

Heritability of respiratory sinus arrhythmia: Dependency on task and respiration rate

In this study, we investigated the genetic and environmental origin of individual differences in respiratory sinus arrhythmia (RSA) during rest and during four stress tasks. We used a multivariate model including age, RSA, and respiration rate. Participants were 208 male and female pairs of middle-aged twins. A model without sex differences, specifying additive genetic and unique environmental factors, showed the best fit across all conditions. Heritability of RSA ranged from 28% to 43%. Correction for respiration rate yielded RSA heritabilities of similar size. The covariance between respiration rate and RSA was best explained by a combination of correlated unique environmental and correlated additive genetic factors. Combined with data from an earlier project. RSA from 317 adolescent and 712 middle-aged individuals of both sexes was available. This large data set showed that (a) sex differences in mean RSA are absent and (b) RSA decreases considerably from adolescence (111.5 ms) to middle age (60.0 ms).     

Volunteers as safety educators in a community campaign on child safety

In 1987 the Dutch Consumer Safety Institute initiated a 1 yearcommunity campaign to reduce home-related injuries of childrenin Nijmegen. The Voluntary Safety Educators Project (VSEP),a main part of this community campaign, was directed at parentswith preschool children. The VSEP was meant to educate parentsin most families in the community through group sessions toimprove their safety behaviour. The aim of the present paper is to describe the developmentof the VSEP and to assess its success. Data were gathered aboutthe recruitment of volunteers, their training and experiencesas safety educators, parents' participation in the VSEP, theirappraisal of the VSEP and the effects of the VSEP on their knowledgeand behaviour related to child safety. The main finding was that far more parents received safety educationthrough interpersonal channels than would have been the caseif volunteers had not been brought into the community campaign.However, the objective, to educate parents in most familiesin the community, was not achieved. Moreover, participatingparents were relatively highly educated. One reason underlying this result is that the small number ofvolunteers that worked for the VSEP was not able to invite parentsin all families during the 1 year period of the campaign. Theother reason is that the participation was selective. This wasprobably due to components of the educational approach itself:the involvement in child safely as such, the characteristicsof the volunteers and/or the educational method used. In developing the VSEP too little attention was given to therecruitment of volunteers and to whether the educational approachwas suitable for parents in the community. It seems worthwhileto develop a new role for volunteers in the promotion of childsafety at the community level. Suggestions are given for fillingthis role and the need for a thorough pretest it stressed.     

Carcinogenicity Study of Auranofin, an Orally Administered Gold Compound, in Mice

Carcinogenicity Study of Auranofin, an Orally Administered GoldCompound, in Mice. Markiewicz, V. R., Saunders, L. Z., Geus,R. J., Payne, B. J. and Hook, J. B. (1988). Fundam Appl Toxicol.11, 277–284. Auranofin, a gold-containing compound, wasadministered to Charles River CO-1 mice for 18 months to assessits possible carcinogenicity. The mice were dosed orally with1.0,3.0, or 6.0 (increased to 9.0 on Day 294) mg/kg/day. Eachdose group and each of two control groups contained 110 malesand 110 females. Survival was greater than 70% at the end ofthe study. No effect of the treatment on neoplastic or nonneoplasticlesions was found. This is in contrast to the results reportedin rats. Auranofin in rats produced a heavy metal nephropathycharacterized by acute coagulative necrosis, subacute renalcortical fibrosis, chronic cytomegaly and karyomegaly, and finallyrenal cortical neoplasia (adenomas and adeno-carcinomas). Thelack of effect of auranofin on tumor incidence in mice suggeststhe findings in rats may be Species specific.