Atropine, pilocarpine, NO system, BPC157 on mydriasis in rats"

Pokazali smo u štakora posebne modulatorne učinke želučanog pentadekapeptida BPC 157 (10^g, 10ng, 10pg/kg) primijenjenog u obliku kapi za oči ili sistemski na dugotrajni (cca 3h) miotski učinak nakon primjene L-NAME (5mg/kg) ili L-arginina (100 mg/kg) na midrijazu uzrokovanu atropinom (2 kapi 1% atropina u svako oko, supstancije primijenjene u stanju maksimalne midrijaze), kao i na midrijazu i miozu uzrokovanu pilokarpinom (2 kapi pilokarpina u svako oko, supstancije primijenjene zajedno i u posttretmanu) te osjetljivost s obzirom na blokadu i stimulaciju NO sistema. Općenito, sve navedene supstancije koje mogu antagonizirati atropinsku i pilokarpinsku midrijazu i također s L-NAME, L-arginin i pilokarpinom uzrokovanu miozu imaju utjecaj na NO sistem. L-NAME i L-arginin miotski učinci su uglavnom paralelni (izraženiji učinak kada su primijenjeni lokalno i zajedno), ali i kompetitivni (uzrokujući nakon intraperitonealne primjene kraće vrijeme vraćanja zjenice u početno normalno stanje kod štakora koji su primili L-NAME i L-arginin zajedno). Primijenjen lokalno ili sistemski, BPC 157 nema učinka na normalnu zjenicu kada se primjeni samostalno, dok utječe na induciranu i miozu i midrijazu. Lokalno primijenjen, u štakora s normalnom zjenicom, BPC 157 povećava miotski efekt L-arginina, antagonizira miotski efekt L-NAME; u antagonizaciji atropinske midrijaze, bez obzira na vlastiti antagonizirajući potencijal, BPC 157 ima aditivni učinak primijenjen s L-argininom, s L-NAME-om i s primijenjenima zajedno L-NAME i L-argininom. Intraperitonealno primijenjen, BPC 157 skraćuje vrijeme mioze koju je uzrokovao intraperitoenalno primijenjeni L-ariginin, L-NAME i njihova kombinacija te ne utječe na njihov antagonizirajući efekt na midrijazu uzrokovanu atropinom. Također, BPC 157 antagonizira pilokarpinsku miozu (skraćujući vrijeme vraćanja u normalno početno stanje i smanjujući maksimalnu midrijazu) i midrijazu (koja kraće traje). Zaključno, atropinska midrijaza na poseban način ovisi o NO sistemu; L-NAME, blokator NOs, i L-Arginin, prekursor NO-a, uzrokuju antagonizaciju i miozu (koja se neutralizira kasnije, poništi), efekt koji do sada nije opisan u literaturi. Midrijaza uzrokovana atropinom i pilokarpinom, mioza uzrokovana s L- NAME, L-arginin i pilokarpinom mogu se, očito, antagonizirati s BPC 157 s obzirom na njegovu interakciju s NO sistemom i funkcijom sfinktera zjenice.In living rats' pupil after either eye drops or systemic administration (intraperitoneal), we revealed particular modulatory effects after gastric pentadecapeptide BPC 157 (10pg, 10ng, 10pg/kg) as well as a common long-standing (cc 3h) miotic effect after L-NAME (5mg/kg) or L-arginine (100mg/kg), and atropine-mydriasis (2 drops of 1% atropine/eye, agents at the maximal atropine-mydriasis) and pilocarpine miosis and mydriasis (2 drops of 1% atropine/eye, agents together ori n posttretman) sensitivity to NO-system blockade and/or stimulation. In general, all these agents might counteract atropine-mydriasis and pilocarpine- mydriasis, and thereby, L-NAME-miosis, L-arginine-miosis and pilocarpine-miosis were NOsensitive. L-NAME and L-arginine miotic effects were mostly parallel (more effectiveness when applied locally and combined), but competitive (providing after intraperitoneal administration sooner returning to normal pupil size in L-NAME+L-arginine-rats). Applied locally or systemically, modulatory BPC 157 counteracting potential characterizes no influence on normal pupils when given alone while BPC 157 affects induced both miosis and mydriasis. Locally, in rat with normal pupil, BPC 157 augments the miotic effect of L-arginine, counteracts the miotic effect of L-NAME; in counteracting atropine-mydriasis, besides own counteracting potential, BPC 157 has an additive effect with L-arginine, with L-NAME and with L-NAME+L-arginine. Intraperitoneally, BPC 157 shortens the miotic effects of intraperitoneal L-arginine, L-NAME, and L-arginine+L-NAME and does not affect their counteracting effect on atropine-mydriasis. Also, BPC 157 counteract pilocarpine-myosis (shortens time and maximal mydriasis) and pilocarpine mydriasis (shorter duration). Concluding, the atropine-mydriasis depends on NO-related mechanisms in a particular way and both L-NAME, a NOS-blocker and L-arginine, a NOS-substrate, exhibit a counteraction and miosis (that could be mutually counteracted), an effect thus far undescribed; the atropine-mydriasis, L-NAME-miosis and L- arginine-miosis, may consequently be counteracted by BPC 157 due to its interactions with the NO-system and sphincter function

Pentadekapeptid BPC 157 skraćuje trajanje anestezije rožnice izazvane tetrakainom i oksibuprokainom kod štakora

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.U ovom istraživanju ispitivali smo međuodnos anestezije rožnice uzrokovane 0,5% tetrakainom odnosno 0,4% oksibuprokainom i pentadekapeptida BPC 157 (0,4 μg/oko) u kombinaciji s inhibitorom nitrid oksida L-NAME (0,1 mg/oko) i/ili supstratom nitrid oksida L-argininom (2 mg/oko) primijenjenim u obliku kapi za oči. Procjenjivali smo anesteziju rožnice (Cochet-Bonnetov esteziometar), nestajanje lezija rožnice (bojenje 10% fluoresceinom) te volumen nastajanja suza (Schirmerov test). Učinak potpunog poništavanja anestezije rožnice uočen je u skupinama koje su primale BPC 157. Oporavak je također nastupio u skupinama koje su primale i supstrat i blokator nitrid oksida. L-arginin skraćuje vrijeme neosjetljivosti rožnice, a uočeno je i smanjenje lezija rožnice te poništavanje smanjenja lučenja suza, ali samo u ranijem kraćem razdoblju, dok se kasnije taj učinak gubi. L-NAME je uzrokovao produženje vremena neosjetljivosti rožnice kao i povećanje lezija rožnice te dodatno smanjenje stvaranja suza. Kada se L-arginin i L-NAME daju zajedno njihov učinak se poništava. Opažene razlike mogu ukazivati na određeni utjecaj i uključenost nitrid oksida (neosjetljivost rožnice naspram nastajanja lezija rožnice i stvaranja suza), što je pokazano primjenom supstrata/blokatora nitrid oksida. Međutim, u bilo kojoj kombinaciji prije ili kasnije, dodatak BPC 157 doveo bi do poništavanja učinka primijenjenih anestetika

Zagreb Amblyopia Preschool Screening Study: near and distance visual acuity testing increase the diagnostic accuracy of screening for amblyopia

Aim To present and evaluate a new screening protocol for amblyopia in preschool children. Methods Zagreb Amblyopia Preschool Screening (ZAPS) study protocol performed screening for amblyopia by near and distance visual acuity (VA) testing of 15 648 children aged 48-54 months attending kindergartens in the City of Zagreb County between September 2011 and June 2014 using Lea Symbols in lines test. If VA in either eye was >0.1 logMAR, the child was re-tested, if failed at re-test, the child was referred to comprehensive eye examination at the Eye Clinic. Results 78.04% of children passed the screening test. Estimated prevalence of amblyopia was 8.08%. Testability, sensitivity, and specificity of the ZAPS study protocol were 99.19%, 100.00%, and 96.68% respectively. Conclusion The ZAPS study used the most discriminative VA test with optotypes in lines as they do not underestimate amblyopia. The estimated prevalence of amblyopia was considerably higher than reported elsewhere. To the best of our knowledge, the ZAPS study protocol reached the highest sensitivity and specificity when evaluating diagnostic accuracy of VA tests for screening. The pass level defined at ≤0.1 logMAR for 4-year-old children, using Lea Symbols in lines missed no amblyopia cases, advocating that both near and distance VA testing should be performed when screening for amblyopia

BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

Providing NO-system importance, we suggest that one single application of the NOS-blocker L-NAME may induce retinal ischemia in rats, and that the stable pentadecapeptide BPC 157 may be the therapy, since it may interact with the NO-system and may counteract various adverse effects of L-NAME application. A rat retinal ischemia study was conducted throughout 4 weeks, including fundoscopy, behavior presentation, tonometry, and histology assessment. Retrobulbar L-NAME application (5 mg/kg; 0.5 mg/0.1 ml saline/each eye) in rats immediately produced moderate generalized irregularity in the diameter of blood vessels with moderate atrophy of the optic disc and faint presentation of the choroidal blood vessels, and these lesions rapidly progressed to the severe stage. The specific L-NAME–induced vascular failure points to normal intraocular pressure (except to very transitory increase upon drug retrobulbar administration). When BPC 157 (10 μg; 10 ng/kg, as retrobulbar application, 1 μg; 1 ng/0.1 ml saline/each eye) is given at either 20 min after L-NAME or, lately, at 48 h after L-NAME, the regular retrobulbar L-NAME injection findings disappear. Instead, fundoscopy demonstrated only discrete generalized vessel caliber irregularity with mild atrophy of the optic disc, and then, quite rapidly, normal eye background and choroidal blood vessels, which remain in all of the subsequent periods. Also, histology assessment at 1, 2, and 4 weeks shows that BPC 157 counteracted the damaged inner plexiform layer and inner nuclear layer, and revealed normal retinal thickness. The poor behavioral presentation was also rescued. Thus, while further studies will be done, BPC 157 counteracted L-NAME–induced rat retinal ischemia

Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine

AIM: To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide (NO) system involvement. ----- METHODS: Male Wistar rats underwent superior anterior pancreaticoduodenal vein (SAPDV)-ligation and were treated with a bath at the ligated SAPDV site (BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 mL bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation (filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein (IAPDV) and superior mesenteric vein (SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO- and oxidative stress [malondialdehyde (MDA)]-levels in duodenum. ----- RESULTS: Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues. ----- CONCLUSION: BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, an effect related to the NO system and reduction of free radical formation

Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: new insights

AIM: To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. ----- METHODS: Medication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath. ----- RESULTS: Commonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 μg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present. ----- CONCLUSION: BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Atropine, pilocarpine, NO system, BPC157 on mydriasis in rats"

Pokazali smo u štakora posebne modulatorne učinke želučanog pentadekapeptida BPC 157 (10^g, 10ng, 10pg/kg) primijenjenog u obliku kapi za oči ili sistemski na dugotrajni (cca 3h) miotski učinak nakon primjene L-NAME (5mg/kg) ili L-arginina (100 mg/kg) na midrijazu uzrokovanu atropinom (2 kapi 1% atropina u svako oko, supstancije primijenjene u stanju maksimalne midrijaze), kao i na midrijazu i miozu uzrokovanu pilokarpinom (2 kapi pilokarpina u svako oko, supstancije primijenjene zajedno i u posttretmanu) te osjetljivost s obzirom na blokadu i stimulaciju NO sistema. Općenito, sve navedene supstancije koje mogu antagonizirati atropinsku i pilokarpinsku midrijazu i također s L-NAME, L-arginin i pilokarpinom uzrokovanu miozu imaju utjecaj na NO sistem. L-NAME i L-arginin miotski učinci su uglavnom paralelni (izraženiji učinak kada su primijenjeni lokalno i zajedno), ali i kompetitivni (uzrokujući nakon intraperitonealne primjene kraće vrijeme vraćanja zjenice u početno normalno stanje kod štakora koji su primili L-NAME i L-arginin zajedno). Primijenjen lokalno ili sistemski, BPC 157 nema učinka na normalnu zjenicu kada se primjeni samostalno, dok utječe na induciranu i miozu i midrijazu. Lokalno primijenjen, u štakora s normalnom zjenicom, BPC 157 povećava miotski efekt L-arginina, antagonizira miotski efekt L-NAME; u antagonizaciji atropinske midrijaze, bez obzira na vlastiti antagonizirajući potencijal, BPC 157 ima aditivni učinak primijenjen s L-argininom, s L-NAME-om i s primijenjenima zajedno L-NAME i L-argininom. Intraperitonealno primijenjen, BPC 157 skraćuje vrijeme mioze koju je uzrokovao intraperitoenalno primijenjeni L-ariginin, L-NAME i njihova kombinacija te ne utječe na njihov antagonizirajući efekt na midrijazu uzrokovanu atropinom. Također, BPC 157 antagonizira pilokarpinsku miozu (skraćujući vrijeme vraćanja u normalno početno stanje i smanjujući maksimalnu midrijazu) i midrijazu (koja kraće traje). Zaključno, atropinska midrijaza na poseban način ovisi o NO sistemu; L-NAME, blokator NOs, i L-Arginin, prekursor NO-a, uzrokuju antagonizaciju i miozu (koja se neutralizira kasnije, poništi), efekt koji do sada nije opisan u literaturi. Midrijaza uzrokovana atropinom i pilokarpinom, mioza uzrokovana s L- NAME, L-arginin i pilokarpinom mogu se, očito, antagonizirati s BPC 157 s obzirom na njegovu interakciju s NO sistemom i funkcijom sfinktera zjenice.In living rats' pupil after either eye drops or systemic administration (intraperitoneal), we revealed particular modulatory effects after gastric pentadecapeptide BPC 157 (10pg, 10ng, 10pg/kg) as well as a common long-standing (cc 3h) miotic effect after L-NAME (5mg/kg) or L-arginine (100mg/kg), and atropine-mydriasis (2 drops of 1% atropine/eye, agents at the maximal atropine-mydriasis) and pilocarpine miosis and mydriasis (2 drops of 1% atropine/eye, agents together ori n posttretman) sensitivity to NO-system blockade and/or stimulation. In general, all these agents might counteract atropine-mydriasis and pilocarpine- mydriasis, and thereby, L-NAME-miosis, L-arginine-miosis and pilocarpine-miosis were NOsensitive. L-NAME and L-arginine miotic effects were mostly parallel (more effectiveness when applied locally and combined), but competitive (providing after intraperitoneal administration sooner returning to normal pupil size in L-NAME+L-arginine-rats). Applied locally or systemically, modulatory BPC 157 counteracting potential characterizes no influence on normal pupils when given alone while BPC 157 affects induced both miosis and mydriasis. Locally, in rat with normal pupil, BPC 157 augments the miotic effect of L-arginine, counteracts the miotic effect of L-NAME; in counteracting atropine-mydriasis, besides own counteracting potential, BPC 157 has an additive effect with L-arginine, with L-NAME and with L-NAME+L-arginine. Intraperitoneally, BPC 157 shortens the miotic effects of intraperitoneal L-arginine, L-NAME, and L-arginine+L-NAME and does not affect their counteracting effect on atropine-mydriasis. Also, BPC 157 counteract pilocarpine-myosis (shortens time and maximal mydriasis) and pilocarpine mydriasis (shorter duration). Concluding, the atropine-mydriasis depends on NO-related mechanisms in a particular way and both L-NAME, a NOS-blocker and L-arginine, a NOS-substrate, exhibit a counteraction and miosis (that could be mutually counteracted), an effect thus far undescribed; the atropine-mydriasis, L-NAME-miosis and L- arginine-miosis, may consequently be counteracted by BPC 157 due to its interactions with the NO-system and sphincter function