Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats

The superior effectiveness of a new pentadecapeptide, BPC 157, on gastrointestinal and liver lesions, in conjunction with an antiinflammatory and analgetic activity was recently noted. In the present study, BPC 157 was tested as either a protective or healing agent in bile duct ligation-induced acute pancreatitis in rats. In addition, the positive influence of BPC 157 on concomitantly developed gastric and duodenal lesions was simultaneously investigated. BPC 157 (10 µg, 10 ng/kg body wt, intraperitoneally or intragastrically) was given prophylactically 1 hr before ligation, whereas the therapy was given once daily beginning with the 24 hr following ligation (last application 24 hr before killing). The effect was investigated at daily intervals until the end of the fifth day after ligation. In the pretreatment regimen, a strong pancreas protection was obtained. When applied in the condition of already established severe acute pancreatitis, an obvious salutary effect was consistently noted. Assessing the appearance of the necrosis, edema, neutrophils, and mononuclears, consistently less necrosis, edema, and neutrophils, but more mononuclears, were found in BPC-treated rats. Likewise, in studies of the serum amylase values, relative to control data, a markedly lower rise (BPC pretreatment regimen) as well as a worsening of the already raised values (BPC therapy regimen) was noted. Along with its beneficial effect on pancreatitis, a positive influence of BPC 157 on the gastric and duodenal lesion course in bile duct-ligated rats was noted in both the pre- and posttreatment regimen. Taken together, in further studies of acute pancreatitis therapy, BPC could be an interesting and useful agent with an additional positive impact on concomitant gastroduodenal pathology.This study was subsidized by grants from the Ministry of Science of the Republic of Croatia and Pliva, Zagreb, Croatia.     

Coronary flow of the infarct artery assessed by transthoracic Doppler after primary percutaneous coronary intervention predicts final infarct size

Coronary microcirculatory function after primary percutaneous coronary intervention (pPCI) in patients with acute myocardial infarction is important determinant of infarct size (IS). Our aim was to investigate the utility of coronary flow reserve (CFR) and diastolic deceleration time (DDT) of the infarct artery (IRA) assessed by transthoracic Doppler echocardiography after pPCI for final IS prediction. In 59 patients, on the 2nd day after pPCI for acute anterior myocardial infarction, transthoracic Doppler analysis of IRA blood flow was done including measurements of CFR, baseline DDT and DDT during adenosine infusion (DDT adeno). Killip class, myocardial blush grade, resolution of ST segment elevation, peak creatine kinase-myocardial band and conventional echocardiographic parameters were determined. Single-photon emission computed tomography myocardial perfusion imaging was done 6 weeks later to define final IS (percentage of myocardium with fixed perfusion abnormality). IS significantly correlated with CFR (r = ?0.686, p < 0.01), DDT (r = ?0.727, p < 0.01), and DDT adeno (r = ?0.780, p < 0.01). CFR and DDT adeno in multivariate analysis remained independent IS predictors after adjustment for other covariates and offered incremental prognostic value in models based on conventional clinical, angiographic, electrocardiographic and enzymatic variables. In predicting large infarction (IS > 20 %), the best cut-off for CFR was <1.73 (sensitivity 65 %, specificity 96 %) and for DDT adeno ≤720 ms (sensitivity 81 %, specificity 96 %). CFR and DDT during adenosine are independent and powerful early predictors of final IS offering incremental prognostic information over conventional parameters of myocardial and microvascular damage and tissue reperfusion.     

N-acetyl-glutamic acid: Evaluation of acute and 28-day repeated dose oral toxicity and genotoxicity

N-acetyl-glutamic acid (NAG) is an endogenously produced mammalian substance and minor constituent of commonly consumed foods. This paper reports the outcome of genotoxicity and acute and repeated dose (28-day) oral toxicology studies conducted with NAG. No evidence of genotoxicity was observed with NAG in in vitro or in vivo studies. No mortalities or evidence of adverse effects was observed in Sprague–Dawley rats following acute oral gavage with NAG at a dose of 2000 mg/kg of body weight. No adverse effects were observed in rats following repeated dose dietary exposure to NAG at target concentrations corresponding to doses of 100, 500, or 1000 mg/kg of body weight/day for 28 days. All rats survived until scheduled sacrifice and no biologically significant or test substance related differences were observed in body weights, feed consumption, clinical signs, functional observational battery (FOB), ophthalmology, hematology, coagulation, clinical chemistry, organ weights or histopathology of any of the treatment groups. Based on the observed results it is concluded that NAG is not genotoxic or acutely toxic. The no-observed-adverse-effect-level (NOAEL) for systemic toxicity from repeated dose (28-day) dietary exposure to NAG was 914 mg/kg of body weight/day for male rats and 1007 mg/kg of body weight/day for female rats.     

Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies

Background

Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies.

Procedure

In a cross-sectional study, patients aged 12–50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records.

Results

Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12–50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12–16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients.

Conclusion

Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.