New studies with stable gastric pentadecapeptide protecting gastrointestinal tract. significance of counteraction of vascular and multiorgan failure of occlusion/occlusion-like syndrome in cytoprotection/organoprotection.

Since the early 1990s, when Robert's and Szabo's cytoprotection concept had already been more than one decade old, but still not implemented in therapy, we suggest the stable gastric pentadecapeptide BPC 157 as the most relevant mediator of the cytoprotection concept. Consequently, it can translate stomach and gastrointestinal mucosal maintenance, epithelium, and endothelium cell protection to the therapy of other tissue healing (organoprotection), easily applicable, as native and stable in human gastric juice for more than 24 h. These overwhelm current clinical evidence (i.e., ulcerative colitis, phase II, no side effects, and no lethal dose (LD1) in toxicology studies), as BPC 157 therapy effectively combined various tissue healing and lesions counteraction. BPC 157 cytoprotection relevance and vascular recovery, activation of collateral pathways, membrane stabilizer, eye therapy, wound healing capability, brain-gut and gut-brain functioning, tumor cachexia counteraction, muscle, tendon, ligament, and bone disturbances counteraction, and the heart disturbances, myocardial infarction, heart failure, pulmonary hypertension, arrhythmias, and thrombosis counteraction appeared in the recent reviews. Here, as concept resolution, we review the counteraction of advanced Virchow triad circumstances by activation of the collateral rescuing pathways, depending on injury, activated azygos vein direct blood flow delivery, to counteract occlusion/occlusion-like syndromes starting with the context of alcohol-stomach lesions. Counteraction of major vessel failure (congested inferior caval vein and superior mesenteric vein, collapsed azygos vein, collapsed abdominal aorta) includes counteraction of the brain (intracerebral and intraventricular hemorrhage), heart (congestion, severe arrhythmias), lung (hemorrhage), and congestion and lesions in the liver, kidney, and gastrointestinal tract, intracranial (superior sagittal sinus), portal and caval hypertension, aortal hypotension, and thrombosis, peripherally and centrally.

Verification of bile acid determination method and establishing reference intervals for biochemical and haematological parameters in third-trimester pregnant women.

OBJECTIVES: The aims of this study were to verify the bile acids (BA) method and to establish reference intervals (RIs) for bile acids (BA) and biochemical and haematological parameters in Croatian pregnant women. METHODS: BA spectrophotometric method verification was performed on Siemens Atellica Solution CH 930 automated analyser using Sentinel reagent. Stability, precision, trueness, linearity, and RIs, as well as lipemia interference were tested according to CLSI guidelines. BA, biochemical, and haematological parameters were measured in serum (BA, biochemical) and whole blood (haematological) samples of fasting healthy third-trimester pregnant women from Croatia (n=121). The establishment of the RIs was done a priori according to the CLSI EP28-A3C:2010 guideline. Selected reference individuals' data were analysed using parametric, non-parametric, and robust methods. RESULTS: Stability study showed that BA are stable in serum samples for 2 days at 20 °C, 14 days at 4-8 °C, and 22 days at -20 °C. The precision study and adult RIs verification met the criteria. Linearity was verified for the concentration range of 3.5-172.1 µmol/L whereas the lipemia interference test showed a positive bias (%) in BA concentration. The determined reference limits generally exhibited better precision for haematological parameters, being lower than the upper recommended value 0.2, unlike biochemical parameters. Haematological parameters showed notable differences between pregnant and non-pregnant women, while many biochemical parameters' RIs remained similar. Only ALT and GGT showed lower non-comparable RI upper limits in the population pregnant women. CONCLUSIONS: Spectrophotometric BA method showed satisfactory performance and all examined parameters were within the set criteria. Moreover, RIs for key biochemical and haematological parameters, including BAs, have been established for the first time in the population of Croatian pregnant women.

Mirror syndrome associated with fetal cardiomyopathy.

Mirror syndrome is a rare condition of generalized maternal oedema caused by fetal hydrops. A 37-year-old patient was admitted to our hospital because of suspected mirror syndrome caused by fetal cardiomyopathy. At 26th week of gestation patient developed bilateral pulmonary oedema as her condition rapidly deteriorated. Consequently, preterm labor was induced, percutaneous evacuation of fetal ascites was performed, and the patient finally vaginally delivered stillborn fetus. Although the initial postpartum period was severely complicated by hemorrhage, the condition of the patient significantly improved later, and she was discharged seven days after delivery. We believe this case is worth presenting due to its rarity and significant perinatal and obstetric challenges in treatment of those patients. Furthermore, preimplantation genetic testing could be performed to prevent at least some of the cases.

Pharmacokinetic Analysis of Ethanol in a Human Study: New Modification of Mathematic Model.

In the pharmacokinetic analysis of ethanol after oral administration, only single- or two-compartment models are used, but their precision in estimating pharmacokinetic parameters might be insufficient. In a recent study, pharmacokinetic analysis using a modified Norberg three-compartment model was performed after oral administration of differently sweetened alcoholic solutions and compared to pharmacokinetic analysis using the classic Widmark model. On three occasions, eight male volunteers consumed differently sweetened alcoholic solutions: non-sweetened, sweetened with sucrose, and sweetened with steviol glycoside. Blood ethanol concentration was determined from samples obtained at t = 15, 30, 60, 90, 120, 180 min after consumption. Pharmacokinetic analysis was performed model independently, using the classic Widmarks model and using the modified Norberg model. Results showed that estimated pharmacokinetic parameters depend on the type of model used. The classic Widmark model in particular overestimated the fraction of absorbed ethanol from the gastrointestinal system to systemic circulation. Furthermore, the type of sweetener also affected pharmacokinetic parameters, although the difference was not statistically significant. In conclusion, the novel pharmacokinetic model, while being more physiological, fits experimental data better and hence is more suitable for modelling real-life alcohol consumption. In addition, the effect of natural non-caloric sweetener steviol glycoside on ethanol pharmacokinetics, analysed for the first time in the current research, might be different when compared to the common-used sweetener sucrose.

New Assessment Tool-Postpartum Functional Assessment Questionnaire.

Background and Objectives: Functional status of the mother after delivery is crucial for performing activities of daily living and caring for the newborn. It is important to assess functional abilities after childbirth in order to improve the quality of postpartum care. The aim of this study is to determine the psychometric properties of the questionnaire and assess the functional abilities after childbirth. Materials and Methods: This study is observational. Postpartum Functional Assessment Questionnaire includes eleven items. 301 women after childbirth, 234 after vaginal birth and 67 after caesarean section participated in the study. An assessment of pain intensity and functional abilities was performed on the first and third day after childbirth. The Factor and Cronbach's alpha analyses were performed to determine the factor structure and internal consistency. Results: The analysis reveals two factors, with seven items loading on factor 1 and four on factor 2. Cronbach's alpha for construct I (Mobility) at the first day was 0.927 and at the third day was 0.913; and for Factor II (Self-care) at the first day was 0.846 and at the third day was 0.894. All between-group differences in pain intensity and functional abilities were highly statistically significant (p < 0.001). Differences between the first and third postpartum day were statistically significant for all variables and all subgroups (p < 0.001). Conclusions: Postpartum Functional Assessment Questionnaire has good psychometric properties and is a valuable tool for use in clinical practice.

Stable Gastric Pentadecapeptide BPC 157 May Recover Brain-Gut Axis and Gut-Brain Axis Function.

Conceptually, a wide beneficial effect, both peripherally and centrally, might have been essential for the harmony of brain-gut and gut-brain axes' function. Seen from the original viewpoint of the gut peptides' significance and brain relation, the favorable stable gastric pentadecapeptide BPC 157 evidence in the brain-gut and gut-brain axes' function might have been presented as a particular interconnected network. These were the behavioral findings (interaction with main systems, anxiolytic, anticonvulsive, antidepressant effect, counteracted catalepsy, and positive and negative schizophrenia symptoms models). Muscle healing and function recovery appeared as the therapeutic effects of BPC 157 on the various muscle disabilities of a multitude of causes, both peripheral and central. Heart failure was counteracted (including arrhythmias and thrombosis), and smooth muscle function recovered. These existed as a multimodal muscle axis impact on muscle function and healing as a function of the brain-gut axis and gut-brain axis as whole. Finally, encephalopathies, acting simultaneously in both the periphery and central nervous system, BPC 157 counteracted stomach and liver lesions and various encephalopathies in NSAIDs and insulin rats. BPC 157 therapy by rapidly activated collateral pathways counteracted the vascular and multiorgan failure concomitant to major vessel occlusion and, similar to noxious procedures, reversed initiated multicausal noxious circuit of the occlusion/occlusion-like syndrome. Severe intracranial (superior sagittal sinus) hypertension, portal and caval hypertensions, and aortal hypotension were attenuated/eliminated. Counteracted were the severe lesions in the brain, lungs, liver, kidney, and gastrointestinal tract. In particular, progressing thrombosis, both peripherally and centrally, and heart arrhythmias and infarction that would consistently occur were fully counteracted and/or almost annihilated. To conclude, we suggest further BPC 157 therapy applications.

Occurrence of Liver Damage and Obstetric Outcomes in Pregnant Women Diagnosed with Pruritus during Pregnancy: A Retrospective Study.

Aim: A retrospective study of the occurrence of liver damage and obstetric outcomes in pregnant women diagnosed with pruritus. Methods: The following parameters were monitored in patients: aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase, bilirubin (direct and total), hemoglobin, platelets, serum bile acid level, age of pregnant women, parity, pregnancy weight gain, birth weight, and gestational age at delivery. A total of 107 patients were included during a five-year period (2016-2020) and classified into three groups. Group A included 17 pregnant women with pruritus without elevated liver enzymes and bilirubin. Group B included 50 pregnant women with pruritus, elevated liver enzymes, and bilirubin. Group C included 40 pregnant women with pruritus and elevated bile acids (regardless of liver enzyme levels). Results: The groups did not significantly differ in patients' age and parity, but there was a statistically significant between-group difference in weight gain during pregnancy. The values of AST, ALT, GGT, LDH, and direct bilirubin were the highest in group B, and serum bile acids were expectedly the highest in group C. There was no statistically significant variation in the onset of labor and mode of delivery between groups. However, groups significantly differed in gestational age at delivery, newborn birthweight, and pregnancy prolongation from the onset of pruritus to delivery. Conclusion: Further study is needed to assess the pathophysiologic mechanisms underlying intrahepatic cholestasis of pregnancy as well as any significant liver damage associated with pregnancy.

Amnion protective cesarean section--method for gentle delivery of preterm and/or VLBW neonates.

UNLABELLED: More than 50 percent of preterm neonates below 28 gestational weeks in our institution are delivered by cesarean section (CS). AIM: To present advantages of less used method of delivery of premature and/or very low birth weight (VLBW) neonates by Amnion Protective Cesarean Section (APCS) when indicated and to review our experience with the method. It can be used in all deliveries by CS with unruptured amniotic membranes, at all gestational ages. MATERIALS AND METHODS: Including criteria were singleton pregnancies, gestation of 26 to 35 weeks and birth body weight between 700 to 1500 g. According to the criteria, during the studied period 10 neonates were delivered by APCS. We compared the outcomes of APCS neonates with ones delivered by coventional CS who matched them in mentioned criteria. RESULTS: Compared to CS cases, APCS neonates had statistically significant better first minute AS. Stay in NICU was shorter for APCS neonates but not statistically significant. From our experience APCS neonates had clinically better appearance (less bruises and hematomas). CONCLUSION: APCS is promising method for delivery of preterm and/or VLBW neonates when indicated, although prospective studies are needed in order to prove its effectiveness compared to conventional CS.

[Neurological disorders in pregnancy]. / Neuroloski poremecaji u trudnoci.

Preeclampsia is characterized by hypertension, peripheral edema and proteinuria, but very often also includes neurologic complications. Neurologic complications of severe preeclampsia are indentical to those of hypertensive encephalopathy. The most common neurologic symptoms are headache, vomiting, mental disorders, visual disturbances, sensorimotor deficits and seizures. Endothelial cell dysfunction is the main cause of multiorgan failure. It is of utmost importance to recognize these symptoms and initiate apropriate therapy. Systemic blood presure must not exceed the cerebrovascular autoregulatory capacity. Serum magnesium level is significantly decreased in pregnant women with severe preeclampsia and cerebral edema. Magnesium has been shown to be effective in reducing the occurrence of seizures in preeclampsia by decreasing neuronal excitability, protecting the endothelium against free radicals and reducing cerebral perfusion.

The influence of alpha-, beta-, and gamma-melanocyte stimulating hormone on acetaminophen induced liver lesions in male CBA mice.

Research over the past decade has indicated that melanocortin peptides are potent inhibitors of inflammation and a promising source of new anti-inflammatory and cytoprotective therapies. The purpose of the present paper is to compare protective effects of alpha-, beta-, and gamma-melanocyte stimulating hormone on acetaminophen induced liver lesions in male CBA mice. Acetaminophen was applied intragastrically in a dose of 150 mg/kg, and tested substances were applied intraperitoneally 1 hour before acetaminophen. Mice were sacrificed after 24 hours and intensity of liver injury was estimated by measurement of plasma transaminase activity (AST and ALT) and histopathological grading of lesions. It was found that alpha-, beta-, and gamma-MSH decrease intensity of lesions by both criteria in a dose-dependent manner.

Dermatologic medication in pregnancy.

In female body, a vast number of skin changes occur during pregnancy. Some of them are quite distressing to many women. Therefore, performing treatment for physiologic skin changes during pregnancy with antiinfective agents, glucocorticosteroids, topical immunomodulators, retinoids, minoxidil, etc., is discussed. Drug administration during pregnancy must be reasonable.

The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. The effect of N(G)-nitro-L-arginine methyl ester and L-arginine.

BACKGROUND: Alcohol disturbances, NO stimulation (by the NO-precursor L-arginine), and/or NO-synthesis blockade (by N(G)-nitro-L-arginine methyl ester, i.e. L-NAME) were challenged with stable gastric pentadecapeptide BPC 157, which inhibits both acute alcohol intoxication and alcohol withdrawal symptoms. MATERIAL/METHODS: Mice received intraperitoneally (i.p.) BPC 157 (10 microg/kg), L-NAME (10 mg/kg), and L-arginine (400 mg/kg), alone or in combination, 5 minutes before or after acute ethanol (4 g/kg i.p.) intoxication or after 0, 3, or 7 hours of withdrawal after drinking 20% alcohol for 13 days. RESULTS: BPC 157 rapidly opposes the strongest disturbance presentations in acute intoxication (sustained ethanol anesthesia, complete loss of righting reflex, no reaction to external stimuli, hypothermia, 25% mortality) and withdrawal (prominent seizures). NO-agents: Aggravation of acute alcohol intoxication and opposition to withdrawal are common, but the later intervals affected by L-arginine and the action throughout the experiment by L-NAME are distinctive. Given together, L-arginine and L-NAME counteract each other, while either the "L-NAME presentation" (acute intoxication) or the "L-arginine presentation" (withdrawal) predominates. BPC157+NO-agent: In acute intoxication (L-NAME predominating in NO-system functioning to aggravate intoxication), both BPC157+L-NAME and BPC157+L-arginine follow the presentation of L-NAME, but without worsened mortality. In withdrawal (L-arginine predominating in NO-system functioning to oppose disturbance symptoms), BPC157+L-NAME follows the presentation of L-NAME, while BPC 157+L-arginine imitates that of L-arginine. CONCLUSIONS: The relationships among pentadecapeptide BPC 157, the NO-system, acute alcohol intoxication, and opposed withdrawal may be important, presenting pentadecapeptide BPC 157 as a suitable alcohol antagonist.

Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats.

Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (alpha-[14C]methyl-L-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent L-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or L-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) L-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on L-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + L-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or temperature effect) has a beneficial activity, which is likely, particular, and mostly related to a rather specific counteraction of 5-HT2A receptors phenomena.

The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice.

The stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W.1419), which was promising in inflammatory bowel disease (PL-10, PLD-116, PL-14736, Pliva) trials, protects against both acute and chronic alcohol-induced lesions in stomach and liver, but also, given peripherally, affects various centrally mediated disturbances. Now, in male NMRI mice BPC 157 (10 pg intraperitoneally, 10 ng and 10 microg, intraperitoneally or intragastrically) (i) strongly opposed acute alcohol (4 g/kg intraperitoneally) intoxication (i.e., quickly produced and sustained anesthesia, hypothermia, increased ethanol blood values, 25% fatality, 90-min assessment period) given before or after ethanol, and (ii) when given after abrupt cessation of ethanol (at 0 or 3 or 7 h withdrawal time), attenuated withdrawal (assessed through 24 hours) after 20%-alcohol drinking (7.6 g/kg) through 13 days, with provocation on the 14th day.