Hemorrhagic mucosal lesions in the stomach in the rat induced by an intragastrical application of 1 ml of 50 or 75% ethanol were aggravated by preceding lung damage provoked by an intratracheal ...instillation of pyrogen-free saline or HCl (pH 1.75) or 50-h exposure to 100% oxygen. Due to the particular preceding aggravating circumstances, these lesions were taken to be of a special kind, rather than ordinary. So far, it is not known whether and how antiulcer agents may influence these lesions. Rats received an intratracheal (i.t.) HCl instillation 1.5 ml/kg HCl (pH 1.75) (lung-lesion), and an intragastric instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), and were sacrificed 1 h after ethanol. Basically, in lung injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for a 1-h observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (PL-10, PLD-116; 10 μg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given /kg, intraperitoneally (i.p.) (1) once, only prophylactically as a pre-treatment (at −1 h), or as a co-treatment (at 0), or only therapeutically (at +18 h or +24 h); (2) repeatedly, combining prophylactic/therapeutic regimens (−1 h)+(+24 h) or (0)+(+24 h), or therapeutic/therapeutic regimens (+18 h)+(+24 h). In general, the antiulcer agents did protect against ethanol gastric lesions regardless of the presence of the severe lung injury, in all of the used regimens. Of note, combining their prophylactic and salutary regimens (at −1 h/+24 h, or at 0/+24 h) may increase the antiulcer potential, and the effect that had been not seen already with single application, became prominent after repeated treatment.
INTRODUCTION The blood supply of the brain gradually reduces with ongoing age, the cerebral cortex undergoes atrophy, causes cognitive inhibition converting to vascular dementia and Alzheimer’s
in ...later stages. The relation between cognitive impairment (CI) and high blood pressure has been long studied in elderly patients, necessitating for further research and evidence on this topic. AIM To study the parameters of arterial stiffness (AS): central blood pressure (CBP), pulse wave velocity (PWV) in patients with hypertension and determine it’s relationship with vascular CI. METHODS AND MATERIALS A systematic literature review was performed using a standardised
published methodology; 25 studies were selected from last 10 years from google search engine, Pubmed central and NCBI with keywords like AS, CBP, PWV, CI. RESULTS PWV was a significant and independently associated with cognitive function when measured with mini mental state examination in an elderly population in Japan. The relationship between high vascular stiffness and CI is explained as the disturbance in regulation of endothelial nitric oxide release. This in turn causes a neuronal energy crisis initiated by cerebral hypoperfusion due to impaired vascular tone and develops CI. As elderly population tend to have an increased risk for arteriosclerosis which is highly predicted by PWV, these patients are highly prone to develop vascular dementia and Alzheimer’s in future. CONCLUSION An inverse relation between AS and cognitive function was found and provided an evidence to vascular hypothesis of vascular dementia and Alzheimer’s. Prospective studies involving these early predictive markers PWV and AS may help in therapeutic intervention and progression of the disease.
Analizirano je 170 slučajeva akutnih otrovanja u 60 pacijenata i 110 pacijentica (srednja dob 31 godina) koji su obrađivani u Hitnoj internoj poliklinici Kliničke bolnice "Merkur" u razdoblju od 1. ...siječnja do 1. studenoga 1999. U 168 (98%) pacijenata otrovanje je bilo namjerno izazvano. Devedeset posto otrovanja dogodilo se kod kuće. U 134 (79%) pacijenata samoubojstvo je pokušano lijekovima. Uzrok akutnog otrovanja u 81 (48%) bili su benzodiazepini, a u 19 (11%) slučajeva antidepresivi. Pretežiti uzrok otrovanja u muškaraca bio je alkohol (u 18 slučajeva, 11%) ili kombinacija alkohola i psihoaktivnog preparata (u 10 slučajeva, 6%). Narkotici su bili uzročnici akutnog otrovanja u 31 (18%) pacijenata i među njima bio je najzastupljeniji kokain. Ostali uzročnici akutnog otrovanja bile su sintetske droge kao ecstasy (3 slučaja, 2%) te udisanje ugljičnog monoksida (6 slučaja, 4%) i klorovodične kiseline (2 slučaja, 1%). U 68 (40%) pacijenata pokušaj suicida bio je posljedica depresije. Prethodnih suicidalnih namjera bilo je u 24 (14%) pacijenata. Na prijemu u Hitnu internu polikliniku bilo je ukupno 50 (29%) komatoznih pacijenata, a uzrok otrovanja kokain u 31 (18%), benzodiazepin u 11 (6%) i alkohol u 8 (5%) slučajeva. Od tih pacijenata na daljnjem tretmanu u Jedinici intenzivne njege zadržana su 24 pacijenta. Smrtni ishod zabilježen je u troje pacijenata visoke dobi (više od 70 godina) koji su se otrovali antidepresivima, a uzrok smrti bile su ventrikularna aritmija i respiratorna depresija. Rezultati ovog istraživanja daju korisne podatke kako za pružanje neposredne medicinske skrbi tako i pri planiranju zdravstvene zaštite u namjerno izazvanim akutnim otrovanjima.
Adiabetogenic alloxan regimen produced lesions in all stomachs of treated animals, either rats (200 mg.kg
–1 s.c.) or mice (400 mg.kg
–1 i.p.). In control animals, the lesions, when developed (i.e. ...24 h following application), appear to be quite sustained, and consistently present also after 1 or 2 weeks. The application of the pentadecapeptide BPC 157 (10 μg or 10 ng.kg
–1 i.p. coadministered together with alloxan) would significantly attenuate these lesions' appearance. This beneficial effect seems to be present in either rats or mice and in either of the tested intervals. Importantly, the beneficial effect seems to be shared by both microgram and nanogram regimens.
A novel gastric pentadecapeptide BPC 157 with different beneficial activities and anticonvulsant effect interacting with GABAergic system could improve diazepam efficacy coadministered (10 microg/kg, ...10 ng/kg i.p.) with diazepam (5.0 mg/kg i.p.) twice daily for 10 days, since diazepam chronic medication would otherwise predispose for diazepam- tolerance/withdrawal development (shorter latency to convulsion after convulsant). In diazepam chronically treated mice, it attenuated diazepam tolerance (provoked by later acute administration of diazepam together with convulsant) and postponed physical dependence/withdrawal effects (provoked by later administration of isoniazid). In tolerance assay, at 42 h after the end of conditioning regimen, shorter preconvulsive latencies than in healthy (non-diazepam conditioned) mice following isoniazid (800 mg/kg i.p.) (as hallmark of tolerance) were observed if diazepam (5.0 mg/kg i.p.) was again given acutely to mice previously conditioned with diazepam alone (use of picrotoxin 3.0 mg/kg i.p., as convulsant, with acute application of diazepam in previously diazepam conditioned mice did not lead to tolerance hallmark). This was completely avoided in diazepam+BPC 157 10 microg or diazepam+BPC 157 10 ng chronically treated animals. In physical dependence assay (isoniazid challenge assessed at 6, 14, 42 and 72 h after conditioning medication), when compared to diazepam non-conditioned healthy mice, in diazepam conditioned mice residual anticonvulsive activity was not present already at the earliest post-conditioning interval (i.e., not different latency to isoniazid-convulsions), whereas shorter preconvulsive latencies (as physical dependence/withdrawal hallmark) were noted in diazepam conditioned mice following isoniazid challenge at 42 h and at 72 h after end of conditioning treatment. In diazepam+BPC 157 10 microg- conditioned mice, a residual anticonvulsive activity (i.e., longer latency to isoniazid convulsion) was noted at 6 h post-conditioning, whereas shorter preconvulsive latencies appeared only at 72 h-post-conditioning period. In conclusion, taken together these data (lack of tolerance development (tolerance studies), prolonged residual anticonvulsive activity, and postponed physical dependence/withdrawal hallmark in diazepam+BPC 157 chronically treated mice) with common benzodiazepines tolerance/withdrawal knowledge, it could be speculated that BPC 157 acts favoring the natural homeostasis of the GABA receptor complex as well as enhancing the GABAergic transmission, and having a mechanism at least partly different from those involved in diazepam tolerance/withdrawal, it may be likely used in further therapy of diazepam tolerance and withdrawal.
In rheumatoid arthritis (RA) kidney is commonly affected organ with clinical presentation characterised by proteinuria (often nephrotic range) and microhematuria followed by chronic renal failure. ...This condition is well recognized as a rheumatoid nephropathy (rheumatoid glomerulonephritis), which is mediated by an immunological inflammation and by nephrotoxic effects of numerous drugs usually used in rheumatoid arthiritis treatment, such as NSAID, DMARD. In the patohistological examination various kinds of associated renal lesions could be seen. The most often are amyloidosis, glomerulonephritis, interstitial nephritis. In this study, we presented 15 patients, 10 women and 5 men, mean age of 60.2 with average rheumatoid arthritis duration of 19.4 years and signs of rheumatoid nephropathy. In all patients renal biopsy was performed with frequency of histopathological findings as follows: amyloidosis in 5 patients, IgA nephropathy in 3 patients, FSGS in 3 patients, mesangial proliferative glomerulonephritis in 3 patients, minimal change disease, pauci-immune glomerulonephritis and thin membrane disease in 1 patient. In all patients (except patient with thin membrane nephropathy) we started immunossuppresive therapy with glucocorticoids in combination with cyclophosphamide or cyclosporin or azatioprine. In conclusion, in all patients with rheumatoid arthritis, parameters of renal function should be monitored and in the case of patologic results, renal biopsy should be be performed. In the treatment of RA patients with related renal disorder, suspected causal drug should be removed from the treatment and specific immunosuppressive therapy initiated.
