The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity.

We highlight the particular aspects of the stable gastric pentadecapeptide BPC 157 pleiotropic beneficial activity (not destroyed in human gastric juice, native and stable in human gastric juice, as a cytoprotection mediator holds a response specifically related to preventing or recovering damage as such) and its possible relations with neurotransmitter activity. We attempt to resolve the shortage of the pleiotropic beneficial effects of BPC 157, given the general standard neurotransmitter criteria, in classic terms. We substitute the lack of direct conclusive evidence (i.e., production within the neuron or present in it as a precursor molecule, released eliciting a response on the receptor on the target cells on neurons and being removed from the site of action once its signaling role is complete). This can be a network of interconnected evidence, previously envisaged in the implementation of the cytoprotection effects, consistent beneficial particular evidence that BPC 157 therapy counteracts dopamine, serotonin, glutamate, GABA, adrenalin/noradrenalin, acetylcholine, and NO-system disturbances. This specifically includes counteraction of those disturbances related to their receptors, both blockade and over-activity, destruction, depletion, tolerance, sensitization, and channel disturbances counteraction. Likewise, BPC 157 activates particular receptors (i.e., VGEF and growth hormone). Furthermore, close BPC 157/NO-system relations with the gasotransmitters crossing the cell membrane and acting directly on molecules inside the cell may envisage particular interactions with receptors on the plasma membrane of their target cells. Finally, there is nerve-muscle relation in various muscle disturbance counteractions, and nerve-nerve relation in various encephalopathies counteraction, which is also exemplified specifically by the BPC 157 therapy application.

Pentadecapeptide BPC 157 as Therapy for Inferior Caval Vein Embolization: Recovery of Sodium Laurate-Post-Embolization Syndrome in Rats.

After inferior caval vein embolization therapy, post-embolization syndrome (sodium laurate 10 mg/kg, 0.1 mL into rat inferior caval vein, assessment at 15, 30, 60 min, prime lung lesions, thromboemboli occluding lung vessels), as a severe occlusion/occlusion-like syndrome, might be resolved as a whole by stable gastric pentadecapeptide BPC 157 therapy. At 5 min after laurate injection, stable gastric pentadecapeptide BPC 157 was implemented as therapy (10 µg/kg, 10 ng/kg intraperitoneally or intragastrically). As before, confronted with the occlusion of major vessel(s) or similar noxious procedures, such as rapidly acting Virchow triad circumstances, the particular effect of the therapy (i.e., collateral pathways activation, "bypassing vascular key", i.e., direct blood flow delivery via activation of azygos vein) assisted in the recovery of the vessel/s and counteracted multiorgan failure due to occlusion/occlusion-like syndrome as a whole in the laurate-injected rats. Along with prime lung lesions and thromboemboli occluding lung vessels, post-embolization syndrome rapidly occurred peripherally and centrally as a shared multiorgan and vessel failure, brain, heart, lung, liver, kidney, and gastrointestinal tract lesions, venous hypertension (intracranial (superior sagittal sinus), portal, and caval), aortal hypotension, progressing thrombosis in veins and arteries and stasis, congested and/or failed major veins, and severe ECG disturbances. Whatever the cause, these were all counteracted, eliminated, or attenuated by the application of BPC 157 therapy. As recovery with BPC 157 therapy commonly and rapidly occurred, reversing the collapsed azygos vein to the rescuing collateral pathway might initiate rapid direct blood delivery and start blood flow reorganization. In conclusion, we suggest BPC 157 therapy to resolve further vascular and embolization injuries.

Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect.

BACKGROUND: Using rat stomach perforation as a prototypic direct lesion applied in cytoprotection research, we focused on the first demonstration of the severe occlusion/ occlusion-like syndrome induced by stomach perforation. The revealed stomach-induced occlusion/occlusion-like syndrome corresponds to the previously described occlusion/occlusion-like syndromes in rats suffering multicausal pathology and shared severe vascular and multiorgan failure. This general point was particularly reviewed. As in all the described occlusion/occlusion-like syndromes with permanent occlusion of major vessels, peripheral and central, and other similar noxious procedures that severely affect endothelium function, the stable gastric pentadecapeptide BPC 157 was resolving therapy. AIM: To reveal the stomach perforation-induced general occlusion/occlusion-like syndrome and BPC 157 therapy effect. METHODS: The procedure included deeply anesthetized rats, complete calvariectomy, laparotomy at 15 min thereafter, and stomach perforation to rapidly induce vascular and multiorgan failure occlusion/occlusion-like syndrome. At 5 min post-perforation time, rats received therapy [BPC 157 (10 µg or 10 ng/kg) or saline (5 mL/kg, 1 mL/rat) (controls)] into the perforated defect in the stomach). Sacrifice was at 15 min or 60 min post-perforation time. Assessment (gross and microscopy; volume) included: Brain swelling, peripheral vessels (azygos vein, superior mesenteric vein, portal vein, inferior caval vein) and heart, other organs lesions (i.e., stomach, defect closing or widening); superior sagittal sinus, and peripherally the portal vein, inferior caval vein, and abdominal aorta blood pressures and clots; electrocardiograms; and bleeding time from the perforation(s). RESULTS: BPC 157 beneficial effects accord with those noted before in the healing of the perforated defect (raised vessel presentation; less bleeding, defect contraction) and occlusion/occlusion-like syndromes counteraction. BPC 157 therapy (into the perforated defect), induced immediate shrinking and contraction of the whole stomach (unlike considerable enlargement by saline application). Accordingly, BPC 157 therapy induced direct blood delivery via the azygos vein, and attenuated/eliminated the intracranial (superior sagittal sinus), portal and caval hypertension, and aortal hypotension. Thrombosis, peripherally (inferior caval vein, portal vein, abdominal aorta) and centrally (superior sagittal sinus) BPC 157 therapy markedly reduced/annihilated. Severe lesions in the brain (swelling, hemorrhage), heart (congestion and arrhythmias), lung (hemorrhage and congestion), and marked congestion in the liver, kidney, and gastrointestinal tract were markedly reduced. CONCLUSION: We revealed stomach perforation as a severe occlusion/occlusion-like syndrome, peripherally and centrally, and rapid counteraction by BPC 157 therapy. Thereby, further BPC 157 therapy may be warranted.

Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats.

Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized rats at 25 mmHg (60 min), 30 mmHg (30 min), 40 mmHg (30 min), and 50 mmHg (15 min) and in esketamine-anesthetized rats (25 mmHg for 120 min)) as a model of multiple occlusion syndrome. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events. Rats with intra-abdominal hypertension (grade III, grade IV) received BPC 157 (10 µg or 10 ng/kg sc) or saline (5 ml) after 10 min. BPC 157 administration recovered the azygos vein via the inferior-superior caval vein rescue pathway. Additionally, intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were reduced, as were the grossly congested stomach and major hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congested inferior caval and superior mesenteric veins, and collapsed azygos vein; thus, the failed collateral pathway was fully recovered. Severe ECG disturbances (i.e., severe bradycardia and ST-elevation until asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, intestinal mucosa villi reduction, crypt reduction with focal denudation of superficial epithelia, and large bowel dilatation were all inhibited. In the liver, BPC 157 reduced congestion and severe sinusoid enlargement. In the lung, a normal presentation was observed, with no alveolar membrane focal thickening and no lung congestion or edema, and severe intra-alveolar hemorrhage was absent. Moreover, severe heart congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. In conclusion, BPC 157 cured primary abdominal compartment syndrome.

THE ROLE OF ULTRASOUND ELASTOGRAPHY IN THE DIAGNOSIS OF PATHOLOGIC CONDITIONS OF TESTICLES AND SCROTUM.

Several years ago, elastography emerged as a potentially very useful ultrasound technique that is currently used in diagnostic workup of the breast, liver and some other organ systems, whereas for other ones it is still mainly in the phase of research. The aim of the study was to compare elasticity index (EI) of testicles using strain elastography in healthy subjects and those with pathologic changes of testicles/scrotum. A total of 117 patients were included in the study. Measurements were performed on a Logiq E9 ultrasound system using strain elastography. In healthy subjects, the mean EI value was 1.34±0.35 for right testis and 1.49±0.47 for left testis. Increased mean EI values were found in the following six conditions: patients with varicocele, infertile patients, solitary testis after orchidectomy of the other testicle because of tumor, patients with testicular tumors, patients after orchidopexy of undescended testicle, and patients with congenitally smaller testicle. There is a paucity of literature data on the use of elastography in testes, as well as on normal elastography values in testicular tissue. Strain elastography was demonstrated to be a valuable method to acquire additional information in patients with pathologic changes in testicles/scrotum. These data provide reference values for further research in a larger sample of subjects.

BPC 157 Therapy and the Permanent Occlusion of the Superior Sagittal Sinus in Rat: Vascular Recruitment.

We show the complex syndrome of the occluded superior sagittal sinus, brain swelling and lesions and multiple peripheral organs lesions in rat. Recovery goes centrally and peripherally, with the stable gastric pentadecapeptide BPC 157, which alleviated peripheral vascular occlusion disturbances, rapidly activating alternative bypassing pathways. Assessments were gross recording, venography, ECG, pressure, microscopy, biochemistry. The increased pressure in the superior sagittal sinus, portal and caval hypertension, aortal hypotension, arterial and venous thrombosis, severe brain swelling and lesions (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus), particular veins (azygos, superior mesenteric, inferior caval) dysfunction, heart dysfunction, lung congestion as acute respiratory distress syndrome, kidney disturbances, liver failure, and hemorrhagic lesions in gastrointestinal tract were all assessed. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally, intragastrically, or topically to the swollen brain at 1 min ligation-time, or at 15 min, 24 h and 48 h ligation-time. BPC 157 therapy rapidly attenuates the brain swelling, rapidly eliminates the increased pressure in the ligated superior sagittal sinus and the severe portal and caval hypertension and aortal hypotension, and rapidly recruits collateral vessels, centrally ((para)sagittal venous collateral circulation) and peripherally (left superior caval vein azygos vein-inferior caval vein). In conclusion, as shown by all assessments, BPC 157 acts against the permanent occlusion of the superior sagittal sinus and syndrome (i.e., brain, heart, lung, liver, kidney, gastrointestinal lesions, thrombosis), given at 1 min, 15 min, 24 h or 48 h ligation-time. BPC 157 therapy rapidly overwhelms the permanent occlusion of the superior sagittal sinus in rat.

Corrigendum: Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats.

[This corrects the article DOI: 10.3389/fphar.2021.718147.].

Fulminant Fournier's gangrene in a patient with gastric cancer treated with ramucirumab and paclitaxel.

Fournier's gangrene (FG) is an uncommon form of necrotizing fasciitis, localized on the external genital organs, perianal region, and abdominal wall, accompanied by thrombosis of the feeding arteries, leading to gangrene of the skin and subcutaneous tissue, with manifestations of rapid clinical progression and multiple organ failure. Ramucirumab is a recombinant human immunoglobulin G1 monoclonal antibody that binds to the extracellular binding domain of vascular endothelial growth factor receptor-2 (VEGFR-2) and prevents the binding of all VEGFR ligands. The literature describes bevacizumab, aflibercept, and regorafenib associated with FG in patients with colorectal cancer. According to our knowledge this is the first report of FG possibly related to ramucirumab in a patient with gastric cancer. If not recognized in time, it can lead to fatal complications.

Successful separation of xypho-omphalopagus conjoined twins with extrauterine twin-twin transfusion syndrome: a case report.

Conjoined twining is a rare medical phenomenon, with an overall prevalence of 1.47 per 100 000 births. This report describes a successful separation of xypho-omphalopagus conjoined twins complicated by unbalanced blood shunting through the porto-systemic anastomoses within the shared liver parenchyma. Significant extrauterine twin-twin transfusion syndrome caused by unbalanced shunting is an extremely rare, and probably under-recognized, hemodynamic complication in conjoined twins necessitating urgent separation. Progressive deterioration with a poor outcome can be prevented if the condition is recognized in a timely manner.

Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157.

Rat inferior caval vein (ICV) ligation (up to the right ovarian vein (ROV)) commonly represents a recapitulation of Virchow: with ligation leading to vessel injury, stasis, thrombosis and hemodynamic changes. We revealed that BPC 157's therapy collectively attenuated or counteracted all these events and the full syndrome. METHODS: We applied BPC 157 (10 µg, 10 ng/kg) as an early regimen or as a delayed therapy. Assessment includes gross assessment by microcamera; microscopy, venography, bleeding, blood pressure, ECG, thermography, MDA and NO-level in plasma and ICV, and gene expression. RESULTS: Direct vein injury, thrombosis, thrombocytopenia, prolonged bleeding were all counteracted. Also, rapid presentation of collaterals and redistribution of otherwise trapped blood volume (bypassing through the left ovarian vein (LOV) and other veins), with venous hypertension, arterial hypotension and tachycardia counteraction were shown. BPC 157-rats presented raised plasma NO-values, but normal MDA-values; in ICV tissue reverted low NO-values and counteracted increased MDA-levels. Altered expression of EGR, NOS, SRF, VEGFR and KRAS in ICV, ROV and LOV revealed increased or decreased levels, while some genes continuously remained unchanged. CONCLUSION: As a new insight, BPC 157 application largely attenuated or even completely eliminated all consequences of ICV ligation in rats.

RADIOLOGICAL IMAGING IN RENAL TRANSPLANTATION.

- Radiological diagnostic methods have a significant role in the preoperative and postoperative care of patients after kidney transplantation. Improvement and innovations in technology, but also the growing experience of the radiologists who deal with kidney transplant patients as part of the transplant team lead to earlier detection of complications in the postoperative period, which are the leading cause of transplant failure. In this article, we describe, through diagnostic imaging examples, detailed evaluation of all possible complications that can occur after kidney transplantation, with evaluation of different possible diagnostic methods that can be used in the preoperative assessment and postoperative follow up and care of the transplanted patient. The goal of this article is to demonstrate and summarize in detail the possible complications of renal transplantation and how to best diagnostically approach them, with special reference to ultrasound which is the main imaging method for this group of conditions.

[Diffuse infantile hepatic hemangioendothelioma: a case report]. / Difuzni infantilni hepatalni hemangioendoteliom: prikaz bolesnika.

Infantile hepatic hemangioendothelioma (IHHE) is the most common benign hepatic tumor in children (12% of hepatic tumors), that usually responds well to therapy and has low mortality rates. In extremely rare cases of diffuse tumors resistant to therapy, size and blood flow can lead to cardiorespiratory failure and death. A 3-month-old male infant presented with respiratory infections and an abdominal mass, with frequent broncho-obstructive attacks. The CT, MRI and DSA exams showed typical morphology of hemangiendothelioma that was proven on histopathological biopsy. The tumor was resistant to standard medical therapy, and its volume led to cardiopulmonary arrest and death at 13 months of age. In rare cases of diffuse therapy-resistant IHHE a liver transplantation should be considered as an earlier treatment.

Resistance index in mural arteries of thickened bowel wall: predictive value for Crohn disease activity assessment in pediatric patients.

OBJECTIVE: To define reliable Doppler parameters in mural arteries of affected bowel loops for quantitative assessment of Crohn disease (CD) activity in pediatric population and compare Doppler parameters with Pediatric Crohn Disease Activity Index (PCDAI). PATIENTS AND METHODS: Thirty-four pediatric patients (7 with inactive, 27 with active disease of different severity; 13 male and 21 female; mean age 13; range 7-18) with CD were prospectively evaluated by Doppler ultrasound (DUS) of affected bowel segments. Using semiquantitative color and power Doppler assessment of vascularization of thickened bowel wall and mesentery, patients were divided in four grades. Spectral measurements (peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI)) of mural arteries were compared with PCDAI. RESULTS: There was a significant difference in distribution of semiquantitative color values between inactive and active group. PSV and EDV values showed no significant difference between inactive and active group, while mean RI was significantly higher in the inactive group. RI was also significantly negatively correlated with PCDAI. CONCLUSION: Intensity of color and power Doppler signals and RI measurement of mural arteries in thickened bowel wall is linked to CD activity and therefore might be of use in pediatric patients.

Post-traumatic high-flow priapism treated by endovascular embolization using N-butyl-cyanoacrylate.

BACKGROUND: Priapism, persistent erection without arousal, can be classified into low-flow (venous or ischemic) and high-flow (arterial or non-ischemic). The diagnosis of high-flow priapism can be confirmed by colour Doppler and arteriography and it is usually treated by the endovascular embolization. CASE REPORT: We present a case of a 20-year-old man with a post-traumatic high-flow priapism as a result of the previous perineal trauma. After a period of watchful waiting and an unsuccessful attempt at endovascular embolization using the resorptive gelatinous foam he was successfully treated by the endovascular embolization using N-butyl-cyanoacrylate. CONCLUSIONS: High-flow priapism can be successfully treated by the endovascular embolization, but the optimal choice of the embolization agent and a careful technique is essential.

[High resolution B-mode and Doppler ultrasound in diagnostic evaluation of Crohn's disease]. / Visokorezolutni B-mod i doplerski ultrazvuk u dijagnostici Crohnove bolesti.

Evaluation of extension and complications as well as assessment of Crohn's disease activity, include different diagnostic methods, of which many utilize ionizing radiation. In our routine work, high resolution B-mode and Doppler ultrasound with measurements of bowel wall thickness and hyperemia, as well as calculation of resistance index of mural arteries and visualisation of extramural changes, represent valuable diagnostic tools in screening, assessment of disease activity, and follow up of the patients with Crohn's disease. Therefore, we reduce the use of ionization radiation in diagnostic workup, which is particulary important considering the fact that Crohn's disease predominantly affects young patients.

Assessment of Crohn's disease activity by doppler ultrasound of superior mesenteric artery and mural arteries in thickened bowel wall: cross-sectional study.

AIM: To define sensitive and reliable Doppler parameters for measurements in the superior mesenteric artery and mural arteries of affected bowel loops used in the assessment of Crohn disease activity. METHODS: We performed cross-sectional study at a tertiary care setting in Zagreb, Croatia, between January 2001 and March 2005. We measured arterial flow in the superior mesenteric artery and affected bowel wall in 138 patients with Crohn disease (74 with active, 64 with inactive disease) and 67 healthy volunteers. The disease activity was determined by the clinical examination, Crohn disease activity index, and standard laboratory tests. Superior mesenteric artery color and pulsed Doppler parameters were peak systolic velocity, end-diastolic velocity, resistance index, mean velocity flow, cross-sectional area, and flow volume. When gut mural vessels were identified, we performed spectral analysis of mural arteries by pulsed Doppler, with a measurement of resistance index. RESULTS: The measurements in the superior mesenteric artery showed statistically and clinically significant difference in flow volume in active group, compared with inactive and control groups (C+/-Q=564+/-263 mL/min for active, 421+/-157 for inactive and 416+/-248 for control group). Affected bowel loops analysis showed significant difference between inactive and active Crohn disease group in wall thickness (3.1+/-1.4 vs 5.0+/-1.8 mm, P<0.001, Mann-Whitney test) while all participants from control group had thickness below 2mm. Intensity of color Doppler signals was different for all groups (P<0.001, chi(2) test) with the highest level of hyperemia in the active group. Resistance index measurements of mural arteries in bowel wall revealed differences between all three groups (0.61+/-0.05 in active group, 0.71+/-0.05 in the inactive group and 0.80+/-0.11 in the control group, P<0.001, Kruskal-Wallis test). CONCLUSION: Intensity of color Doppler signals and resistance index measurements of mural arteries in the thickened bowel wall can be used as quantitative diagnostic tool in the assessment of Crohn disease activity.