Indacrinone (MK-196) - a specific inhibitor of the voltage-dependent CI- permeability in toad skin

The effect of indacrinone (MK-196) on Cl^- transport through toad (Bufo bufo) skin epithelium was studied by the voltage clamping technique. At the transepithelial potential, V = 50 mV (serosal bath grounded) the unidirectional fluxes, governed by a Cl^- self-exchange diffusion pathway, were not affected by 1 mM racemic MK-196 in the outer bath. Likewise at V = 0 mV, the unidirectional fluxes as well as the active (net) inward flux of Cl^- were unaffected by MK-196. Voltage clamping the epithelium in the physiological range of potentials activated a Cl^- specific passive conductance that saturated for V ±– 90 mV. The influx and efflux of Cl^- through this pathway were inhibited by MK-196, and the (passive) Cl^- current was inhibited in a dose-dependent way for [MK-196] ± 50 μM with about 70% inhibition for [MK-196] = I mM. The maximum Cl^- conductance was decreased without shifting the position along the V-axis of the inverted S-shaped conductance–voltage relationship. The time constants for the voltage-stimulated Cl^- conductance activation were not affected by MK-196 (50 μM ± [MK-196] ± 1 mM). The (+) and (–) isomers and racemic MK-196 affected the voltage-dependent Cl^- conductance in similar ways. It is concluded that MK-196 has the properties of a Cl^- channel blocker which is specific for the voltage-dependent Cl^- permeability of the epithelium. The time course for development of inhibition exhibited a fast (min) and a slow (h) component. The fast component may reflect a direct interaction of MK-196 with an extracellular site of the Cl^- channel, whereas the slow one may reflect impairment of a metabolic pathway regulating the Cl^- permeability, or an interaction of MK-196 with a cytoplasmic site of the anion permeation pathway.     

A comparison between naturally occurring macroamylasaemia and macroamylasaemia induced by hydroxyethyl-starch

Macroamylasaemia was produced in vitro by incubation of hydroxyethylstarch with serum, and in vivo by intravenous infusion of hydroxyethylstarch. Gel filtration on Sephadex G-100 revealed distinct differences in molecular size distribution between such hydroxyethylstarch-induced macroamylase and the usual form of naturally occurring macroamylase which was observed in a few patients from our hospital. Further studies demonstrated that the gel filtration elution pattern of amylase activity in serum containing hydroxyethylstarch-induced macroamylase is significantly altered with time in vitro and in vivo, probably because of an enzymatic degradation of the hydroxyethylstarch components of the macromolecular complexes. In a healthy volunteer the serum amylase activity was elevated to a maximum of 797 u/l and the renal clearance rate of amylase was diminished to a minimum of 0.3 ml/min after infusion of 500 ml of a 6% solution of hydroxyethylstarch, as compared to 300 u/l, and 0.95 ml/min, respectively, during the pre-infusion period.     

Familial hemiplegic migraine: a clinical comparison of families linked and unlinked to chromosome 19

We compared the clinical characteristics of 50 patients from three unrelated families with familial hemiplegic migraine (FHM) linked to chromosome 19, with those of 20 patients from two families with FHM not linked to chromosome 19. We found no significant differences for age at onset, frequency and duration of attacks, duration of the paresis, and occurrence of basilar migraine symptoms. In the linked families, significantly more patients reported unconsciousness during attacks (39%, vs 15%; p<0.05) and provocation of attacks by mild head trauma (70% vs 40%; p< 0.05). In one linked family patients also displayed chronic progressive cerebellar ataxia, whereas in one unlinked family benign infantile convulsions occurred in addition to FHM. Interestingly, so far an association with cerebellar ataxia was only described in chromosome 19-linked families. FHM linked to chromosome 19 and FHM unlinked to chromosome 19 do not differ with respect to clinical features.     

Red cell loss following orthopedic surgery: the case against postoperative blood salvage

BACKGROUND: Expensive devices have been developed for the collection and transfusion of blood salvaged after hip or knee arthroplasty. STUDY DESIGN AND METHODS: The volume of salvaged red cells was measured for the first 6 hours after operation. This volume was compared to total red cell loss during hospitalization and to the volume of allogeneic red cells transfused. RESULTS: Mean postoperative red cell loss in 31 patients following hip replacement was 55 +/− 29 mL and that in 20 patients following knee replacement was 121 +/− 50 mL. The 6-hour wound drainage represented 8.7 and 16.8 percent of overall red cell loss during hospitalization for hip and knee replacement, respectively. The transfusion of postoperatively salvaged red cells would have supplanted transfusion of less than one-third of a unit of allogenic blood after hip replacement and two-thirds of a unit after knee replacement. Only three patients (5.9%) lost red cell volume in the drainage equivalent to or in excess of 1 unit of red cells (180 mL). The volume of red cells salvaged postoperatively bore no relationship to perioperative red cell losses as a whole. CONCLUSION: The relatively small red cell loss in the postoperative period in most arthroplasty patients does not appear to justify the routine use of this technique for the recovery of autologous blood.     

über Osteoakusie und deren Beziehungen zur Vibrationsempfindung

Ohne Zusammenfassung     

TLR2 activation by proteosomes promotes uptake of particulate vaccines at mucosal surfaces

Proteosome-based vaccines have TLR2-based adjuvant activity and show promise for mucosal immunization. We examined the effects of proteosomes on mucosal uptake in Peyer's patches in vivo. Proteosomes accelerated transepithelial transport of microparticles by M cells and induced migration of dendritic cells (DCs) into the follicle-associated epithelium (FAE); both effects were dependent on TLR2. Proteosomes induced the release of the DC-attracting chemokine MIP3alpha from Caco-2 epithelial cells in vitro. In HEK cells, proteosome-mediated MIP3alpha release was dependent on TLR2 expression and matrix metalloproteinase activation. Thus, TLR2 activation by proteosomes may promote mucosal uptake of particulate vaccines, and this may contribute to their adjuvanticity.     

Short-term outcomes of a program developed to inculcate research essentials in undergraduate medical students

Background:

Participation in research during undergraduate studies may increase students’ interest in research and inculcate research essentials in them.

Aims:

The purpose of this study was to evaluate the effectiveness of the mentored student project (MSP) program.

Settings and Design:

In the MSP program, students in groups (n = 3 to 5) undertook a research project, wrote a scholarly report, and presented the work as a poster presentation with the help of a faculty mentor. To begin with, the logic model of the program was developed to identify short-term outcomes of the program on students, mentors, and the institution. A quasi-experimental design was used to measure the outcomes.

Materials and Methods:

A mixed method evaluation was done using a newly-developed questionnaire to assess the impact of the MSP on students’ attitude, a multiple-choice question (MCQs) test to find out the impact on students’ knowledge and grading of students’ project reports and posters along with a survey to check the impact on skills. Students’ satisfaction regarding the program and mentors’ perceptions were collected using questionnaires. Evidence for validity was collected for all the instruments used for the evaluation.

Statistical Analysis:

Non-parametric tests were used to analyze data. Based on the scores, project reports and posters were graded into A (>70% marks), B (60-69% marks), and C (<59% marks) categories. The number of MSPs that resulted in publications, conference presentation and departmental collaborations were taken as impact on the institution.

Results:

Students’ response rate was 91.5%. The students’ attitudes regarding research changed positively (P = 0.036) and score in the MCQ test improved (P < 0.001) after undertaking MSP. Majority of project reports and posters were of grade A category. The majority of the items related to skills gained and satisfaction had a median score of 4. The MSPs resulted in inter-departmental and inter-institutional collaborations, 14 publications and 15 conference presentations. An area for improvement noted was to have the MSP implemented in the curriculum without increasing students’ overall workload and stress.

Conclusion:

The study identified strengths and weaknesses of the MSP program. Our model of undergraduate research project may be incorporated in undergraduate medical programs to foster positive attitude and knowledge base about scientific research and to instil research skills among students.KEY WORDS: Attitude, knowledge, mentored, outcome, research, skills, student