In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro.

Recently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsions, and (iv) lidocaine-induced HEK293 cell depolarisation. BPC 157 applications (intraplantar, intraperitoneal, and intragastric) were given (i) immediately after lidocaine, (ii) 10 min after, or (iii) 5 min before. The BPC 157/NO-system relationship was verified with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together, in axillary and spinal intrathecal blocks. BPC 157 applied immediately after lidocaine or 5 min before the application of lidocaine considerably ameliorated plantar presentation. BPC 157 medication considerably counteracted lidocaine-induced limb function failure; L-NAME was counteracted; L-arginine exhibited counteraction when given immediately after lidocaine, but prolongation was seen when given later. Given together, prophylactically or therapeutically, L-NAME and L-arginine (L-NAME + L-arginine) counteracted the other's response. BPC 157 maintained its original response when given together with L-NAME or L-arginine. When BPC 157 was given together with L-NAME and L-arginine, its original response reappeared. BPC 157 antagonised the lidocaine-induced bradycardia and eliminated tonic-clonic convulsions. Also, BPC 157 counteracted the lidocaine-induced depolarisation of HEK293 cells. Thus, BPC 157 has antidote activity in its own right against lidocaine and local anesthetics.

Pentadecapeptide BPC 157 shortens duration of tetracaine- and oxybuprocaine-induced corneal anesthesia in rats.

We focused on the relationship of 0.5% tetracaine- and 0.4% oxybuprocaine-induced corneal anesthesia in rats, and pentadecapeptide BPC 157 (0.4 µg/eye), along with nitric oxide synthase (NOS) inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) (0.1 mg/eye) and/or NOS substrate L-arginine (2 mg/eye), applied in the form of eye drops. We assessed corneal sensitivity recovery (Cochet-Bonnet esthesiometer), corneal lesion elimination (staining with 10% fluorescein) and decrease in tear volume (Schirmer test). BPC 157 administration had a full counteracting effect. Recovery also occurred in the presence of NOS blockade and NOS substrate application. L-arginine eventually shortened duration of corneal insensitivity and exerted corneal lesion counteraction (and counteraction of tetracaine-induced decrease of tear volume) only in earlier but not in later period. L-NAME application led to longer duration of corneal insensitivity, increase in corneal lesions and decrease in tear volume. When L-NAME and L-arginine were applied together, they antagonized each other's effect. These distinctions may indicate particular NOS involvement (corneal insensitivity vs. corneal lesion along with tear production), distinctively affected by the administration of NO agents. However, additional BPC 157 co-administration would re-establish counteraction over topical ophthalmic anesthetic-induced effect, be it in its early or late course. We suggest BPC 157 as an antidote to topical ophthalmic anesthetics.

Impact of a recruitment campaign on students' applications to medical school.

OBJECTIVE: Medical schools might benefit if they have information about the activities that may help them to increase the number of applicants with superior academic qualifications. METHODS: The study was carried out at the Split University School of Medicine, Croatia. Medical school applicants were surveyed in 2007 and 2009. Promotional activities consisted of presentations on medical education covering six general high-schools in 2008, and a presentation on regional television, aired in 2008 and 2009 shortly before the admission term. RESULTS: The survey response rate was 79% (299/379). The number of applicants in 2009 increased by 37% and the percentage of applicants from general high schools increased by 10%, in relation to 2007. The percentage of students with the best grades in all four years of high school was 42% in the both surveys. Presumed quality was a major influencing factor for choosing Split University Medical School. However, the medical school in the Croatian capital remained the first choice for students. Only a few applicants stated that the medical schools' promotional campaigns influenced their decision about where to study; 9.7% and 1.5%, respectively. CONCLUSION: Presentations in elected general high schools and a television campaign should be further explored as possible activities that regional schools may use to recruit potential applicants.

Expression of calcium/calmodulin-dependent protein kinase II and pain-related behavior in rat models of type 1 and type 2 diabetes.

BACKGROUND: Abnormalities in peripheral nerves and dorsal root ganglia are noticed in the early stage of experimentally provoked diabetic neuropathy. Enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) may have a modulating role in diabetic neuropathy because of its role in calcium homeostasis. METHODS: A model of type 1 diabetes mellitus (DM1) was induced with 55 mg/kg of the streptozotocin and for DM2 induction a combination of high-fat diet and low-dose streptozotocin (35 mg/kg) was used. Pain-related behavior was analyzed using thermal and mechanical stimuli. Two weeks and 2 months after induction of diabetes rats were euthanized, and the expression of CaMKII and its isoforms in the dorsal root ganglia were analyzed using immunofluorescence. RESULTS: Both types of diabetes were successfully induced, as confirmed by hyperglycemia. Increased pain-related behavior became evident in DM1 rats in 2 weeks after diabetes induction, but not in DM2 rats. The expression of total CaMKII and the phosphorylated α isoform of CaMKII increased in DM1 animals concurrently with pain-related behavior. Expression of α, ß, γ, and δ isoforms in DM1 animals and expression of total CaMKII and all of its analyzed isoforms in DM2 animals remained unchanged. CONCLUSIONS: Our findings may indicate involvement of CaMKII in transmission of nociceptive input early in DM1, but not in DM2. CaMKII may be a suitable pharmacological target for diabetic neuropathy.

Analysis of the elective curriculum in undergraduate medical education in Croatia.

CONTEXT: Elective courses are a significant part of undergraduate medical education throughout the world, but the value provided by these courses and the reasons for choosing particular elective courses have not been studied extensively. OBJECTIVES: The aim of this study was to investigate medical and dental students' experiences of elective courses in undergraduate medical education in Croatia and to gather students' recommendations for the improvement of elective courses. METHODS: Medical and dental students studying under the Bologna curriculum were given a questionnaire in which they were asked for their opinions of elective courses and their suggestions as to how they might be improved. Data on elective courses were obtained from medical schools' administrative offices. RESULTS: The survey response rate was 92% (834/903). Medical students gave elective courses an average grade of 3.44 out of 5, whereas dental students gave a lower average of 3.15. Students' suggestions for change included introducing more practical work and recognising international student exchanges and attendance at conferences as elective options. A third of students indicated that teachers should be given additional training in leading elective courses. Analysis of the curriculum showed that elective courses in Croatian medical schools are very heterogeneous in terms of their content and the number of credits and assessment methods they involve, and are very conservative in that only structured courses are offered. Students cannot design their own courses or take more elective courses than represent 10% of their total number of credits. CONCLUSIONS: Student opinion should be consulted when medical schools venture into the elective curriculum so that students can feel that they are really benefiting from these subjects. Students would welcome new and personally designed strands. Elective courses are a significant part of medical education and therefore their quality and purpose need to be assessed regularly in order to ensure that they meet students' needs.