Fourier Transform Infrared Spectroscopy Reveals Molecular Changes in Blood Vessels of Rats Treated with Pentadecapeptide BPC 157.

Recently, it was found that when confronted with major vessel occlusion and vascular failure, stable gastric pentadecapeptide BPC 157 therapy might rapidly functionally improve minor vessels to take over the function of disabled major vessels, reorganize blood flow, and compensate failed vessel function. We focused on the BPC 157 therapy effect obtained by giving 10 ng/kg ip to rats 5 min before sacrifice on the rat thoracic aorta, which we assessed with Fourier transform infrared spectroscopy (FTIR) 90 min thereafter. We applied a principal component analysis (PCA). The PCA model showed, with a clear distinction being mostly due to the PC1 score, differences between the spectra of BPC 157- and saline-treated rats. The comparison of the averaged spectra of these two groups with their differential spectrum and PC loadings allowed us to identify the parts of the FTIR spectra that contributed the most to the spectral separation of the two observed groups. The PC1 loadings and the differential spectrum showed that the main bands affecting the separation were the amid I band around 1650 cm-1, the amid II band around 1540 cm-1, and the vibrational band around 1744 cm-1. Fitting the spectral range between 1450 and 1800 cm-1 showed changes in protein conformation and confirmed the appearance of the vibrational band at 1744 cm-1. Controls had a substantially more intense vibrational band at 1744 cm-1. These spectral results showed the cells from saline-treated (control) rats to be in the early stage of cell death, while the samples from BPC 157-rats were protected. Thus, BPC 157 therapy changed the lipid contents and protein secondary structure conformation, with a rapid effect on vessels, within a short time upon application.

Therapy Effect of the Stable Gastric Pentadecapeptide BPC 157 on Acute Pancreatitis as Vascular Failure-Induced Severe Peripheral and Central Syndrome in Rats.

We revealed the therapy effect of the stable gastric pentadecapeptide BPC 157 (10 µg/kg, 10 ng/kg ig or po) with specific activation of the collateral rescuing pathways, the azygos vein, on bile duct ligation in particular, and acute pancreatitis as local disturbances (i.e., improved gross and microscopy presentation, decreased amylase level). Additionally, we revealed the therapy's effect on the acute pancreatitis as vascular failure and multiorgan failure, both peripherally and centrally following "occlusion-like" syndrome, major intoxication (alcohol, lithium), maintained severe intra-abdominal hypertension, and myocardial infarction, or occlusion syndrome, and major vessel occlusion. The application-sacrifice periods were ligation times of 0-30 min, 0-5 h, 0-24 h (cured periods, early regimen) and 4.30 h-5 h, 5 h-24 h (cured periods, delayed regimen). Otherwise, bile duct-ligated rats commonly presented intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, gross brain swelling, hemorrhage and lesions, heart dysfunction, lung lesions, liver and kidney failure, gastrointestinal lesions, and severe arterial and venous thrombosis, peripherally and centrally. Unless antagonized with the key effect of BPC 157 regimens, reversal of the inferior caval and superior mesenteric vein congestion and reversal of the failed azygos vein activated azygos vein-recruited direct delivery to rescue the inferior-superior caval vein pathway; these were all antecedent to acute pancreatitis major lesions (i.e., acinar, fat necrosis, hemorrhage). These lesions appeared in the later period, but were markedly attenuated/eliminated (i.e., hemorrhage) in BPC 157-treated rats. To summarize, while the innate vicious cycle may be peripheral (bile duct ligation), or central (rapidly developed brain disturbances), or peripheral and central, BPC 157 resolved acute pancreatitis and its adjacent syndrome.

Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats.

We revealed that the stable gastric pentadecapeptide BPC 157, a useful peptide therapy against isoprenaline myocardial infarction, as well as against isoprenaline myocardial reinfarction, may follow the counteraction of the recently described occlusion-like syndrome, induced peripherally and centrally, which was described for the first time in isoprenaline-treated rats. BPC 157 (10 ng/kg, 10 µg/kg i.p.), L-NAME (5 mg/kg i.p.), and L-arginine (200 mg/kg i.p.) were given alone or together at (i) 30 min before or, alternatively, (ii) at 5 min after isoprenaline (75 or 150 mg/kg s.c.). At 30 min after isoprenaline 75 mg/kg s.c., we noted an early multiorgan failure (brain, heart, lung, liver, kidney and gastrointestinal lesions), thrombosis, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension, in its full presentation (or attenuated by BPC 157 therapy (given at 5 min after isoprenaline) via activation of the azygos vein). Further, we studied isoprenaline (75 or 150 mg/kg s.c.) myocardial infarction (1 challenge) and reinfarction (isoprenaline at 0 h and 24 h, 2 challenges) in rats (assessed at the end of the subsequent 24 h period). BPC 157 reduced levels of all necrosis markers, CK, CK-MB, LDH, and cTnT, and attenuated gross (no visible infarcted area) and histological damage, ECG (no ST-T ischemic changes), and echocardiography (preservation of systolic left ventricular function) damage induced by isoprenaline. Its effect was associated with a significant decrease in oxidative stress parameters and likely maintained NO system function, providing that BPC 157 interacted with eNOS and COX2 gene expression in a particular way and counteracted the noxious effect of the NOS-blocker, L-NAME.

Extracorporeal blood purification is associated with improvement in biochemical and clinical variables in the critically-ill COVID-19 patients.

This study tried to investigate the impact of oXiris filter on both clinical and laboratory parameters in critically-ill COVID-19 intensive care unit (ICU) patients receiving extracorporeal blood purification and the clinical setting for the initiation of therapy. A consecutive sample of 15 ICU patients with COVID-19 was treated with oXiris membrane for blood purification or for support of renal function due to acute kidney injury. We have included 19 non treated ICU COVID-19 patients as a control group. Two chest x-rays were analyzed for determining the chest x-ray severity score. We have found a significant decrease of SOFA score, respiratory status improved and the chest x-ray severity score was significantly decreased after 72 h of treatment. IL-6 significantly decreased after 72 h of treatment while other inflammatory markers did not. Respiratory status in the control group worsened as well as increase in SOFA score and chest x-ray severity score. Survived patients have shorter time from the onset of symptoms before starting with extracorporeal blood purification treatment and shorter time on vasoactive therapy and invasive respiratory support than deceased patients. Critically-ill patients with COVID-19 treated with extracorporeal blood purification survived significantly longer than other ICU COVID-19 patients. Treatment with oXiris membrane provides significant reduction of IL-6, leads to improvement in respiratory status, chest x-ray severity score, and reduction of SOFA score severity. Our results can suggest that ICU COVID-19 patients in an early course of a disease could be potentially a target group for earlier initiation of extracorporeal blood purification.

Satisfaction of Parents and Caregivers with Dental Treatment of Children Under General Anesthesia in a Day Care Surgery Setting.

Objective: The aim of this study was to examine the satisfaction of parents and caregivers of patients who underwent dental treatment in general anesthesia (GA) in a day-care surgery setting. Material and Methods: Anonymous questionnaire was sent to parents/caregivers of patients who underwent full mouth restoration in GA. The survey consisted of 4 parts: general data, data about procedure, satisfaction with various aspects of care and the perception of parents/caregivers about the condition of their child in relation to the time before dental treatment in GA. Results: 66 parents/caregivers (30.5%) responded to the questionnaire. Overall satisfaction with the treatment was high (4.69). Respondents expressed the highest degree of satisfaction with communication with nurses (4.92), and the lowest with the waiting time for the procedure (3.89). Parents/caregivers of patients who reported difficulty eating expressed significantly lower overall satisfaction than the subjects whose children did not report difficulty eating. Also, the more treatments the patients underwent, the lower was the overall satisfaction than of those subjects whose children were never treated in such a manner before. Conclusions: Since patient satisfaction has a beneficial impact on treatment outcome and adherence to preventive recommendations, all health care providers should strive to achieve it.

Post-Discharge Complications of Dental Treatment in General Anesthesia Performed in a Day-Care Service.

OBJECTIVE: To review the frequency and management of post-discharge complications in patients who underwent dental treatment in general anesthesia (GA) in a day-care surgery setting and identify the factors that increase the risk for these complications. MATERIAL AND METHODS: Anonymous questionnaire was sent to parents/caregivers of patients who underwent full mouth restoration in GA at our institution between 1st January 2017 and 31st July 2019. Demographic and clinical data of patients as well as the data about the occurrence and management of complications were collected. RESULTS: Sixty-six parents/caregivers (30.5%) responded to the questionnaire. Most frequent complications were drowsiness and pain in 40(60.6%) patients. Complications were managed by parents or caregivers with conservative measures at home in 57(91.9%) cases. Phone consultation with dentist was required in 5(8.1%) cases. One patient (1.6%) was readmitted. Younger age and diagnosis were associated with increased risk for drowsiness. CONCLUSION: Post discharge complications of dental treatment in GA in a day-care service are common and they can be managed by parent/caregiver with conservative measures at home. The rate of readmission is low. Dental treatment in GA in a day-care service is a safe procedure that can be performed with acceptable risk in carefully selected patients.

In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro.

Recently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsions, and (iv) lidocaine-induced HEK293 cell depolarisation. BPC 157 applications (intraplantar, intraperitoneal, and intragastric) were given (i) immediately after lidocaine, (ii) 10 min after, or (iii) 5 min before. The BPC 157/NO-system relationship was verified with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together, in axillary and spinal intrathecal blocks. BPC 157 applied immediately after lidocaine or 5 min before the application of lidocaine considerably ameliorated plantar presentation. BPC 157 medication considerably counteracted lidocaine-induced limb function failure; L-NAME was counteracted; L-arginine exhibited counteraction when given immediately after lidocaine, but prolongation was seen when given later. Given together, prophylactically or therapeutically, L-NAME and L-arginine (L-NAME + L-arginine) counteracted the other's response. BPC 157 maintained its original response when given together with L-NAME or L-arginine. When BPC 157 was given together with L-NAME and L-arginine, its original response reappeared. BPC 157 antagonised the lidocaine-induced bradycardia and eliminated tonic-clonic convulsions. Also, BPC 157 counteracted the lidocaine-induced depolarisation of HEK293 cells. Thus, BPC 157 has antidote activity in its own right against lidocaine and local anesthetics.

Pentadecapeptide BPC 157 shortens duration of tetracaine- and oxybuprocaine-induced corneal anesthesia in rats.

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.

Challenges in anesthesia personalization: resolving the pharmacogenomic puzzle.

Clinicians are witnessing differences in the doses required for induction and maintenance of anesthesia, as well as prolonged recovery in some patients. Predictable factors like patient characteristics, factors related to the procedure, pharmacological characteristics of anesthetics and adjunctive drugs, might explain some of the observed differences. However, the role of various polymorphisms of genes encoding for drugs' molecular targets, transporters and metabolic enzymes can have a significant impact on anesthesia outcome, too. In the present paper, we critically discuss pharmacological characteristics of the most common drugs used in anesthesia, with a focus on the possible genetic background of unpredictable diversities in anesthesia outcomes.

Dental Treatment Under General Anesthesia in a Day Care Surgery Setting.

OBJECTIVE: To analyze data on full-mouth rehabilitation under general anesthesia (GA) performed at the University Clinical Hospital Zagreb with emphasis on patient characteristics, type of procedure and postoperative complications. MATERIALS AND METHODS: Retrospective chart review of 100 patients treated under GA at the Dental clinic's day care surgery. Patient's demographic (sex, age) and clinical data (diagnosis, GA technique, intubation type, procedure duration, number of carious teeth, presence of visible calculus, number of sealed teeth, fillings, extractions and endodontic treatments, discharge time, postoperative complications) were registered. RESULTS: Eighty patients were treated under GA because of noncompliance due to different reasons and twenty patients because of either their poor physical condition or extensive dental procedure. Median DMFT per patient was 9(0-21). Eighty nine patients underwent full-mouth dental restoration and 11 patients underwent other types of procedures. Ninety-six patients were safely discharged the same day. Four patients experienced postoperative complications and three of them were hospitalized for another 24-48 hours for postoperative follow-up. CONCLUSION: Patients with physical and/or intellectual disabilities have higher caries activity and increased dental treatment needs compared to the general population. Dental treatment under GA in day care service is a safe and effective way of providing dental care for noncompliant patients.

Etomidate in neuroanesthesia for aneurysmal clipping in child with confirmed allergies to general anesthetics.

BACKGROUND: Etomidate may be given in continuous infusion for maintenance of general anesthesia, although that practice is rarely seen due to beliefs that it has possibility of interfering with cortisol synthesis. However, etomidate is sometimes preferable choice as it has least influence on hemodynamics and rarely causes allergic reactions. CASE DESCRIPTION: We describe a case of 13-year-old boy with aneurysm of left middle cerebral artery, planned for aneurysmal clipping, and previously treated for ruptured aneurysm of right middle cerebral artery. As he was tested and proved allergic to most of the anesthetic drugs, and stable hemodynamic conditions were of most importance during planned neurosurgery, general anesthesia was maintained with etomidate infusion. He was prepared with metilprednisolon, antihistaminic, and ranitidine before the surgery. Cortisol and adrenocorticotropic hormone levels were measured on three consecutive postoperative days. Only cortisol value, in the morning the day after the surgery, was below reference range, with the values back to normal until that evening. He was dismissed from the intensive care unit with Glasgow Coma Score 15. CONCLUSION: Etomidate may be a choice for neuroanesthesia in specific group of people. We have good experience with our algorithm for continuous infusion of etomidate, with serum cortisol values in the reference range, if corticosteroids were not given before the surgery. Administration of metilprednisolon may diminish influence of perioperative stress on cortisol synthesis inhibition.

PbtO2 monitoring in normobaric hyperoxia targeted therapy in acute subarachnoidal hemorrhage.

BACKGROUND: Low brain tissue oxygen tension (PbtO2), or brain hypoxia, is an independent predictor of poor outcome. Increasing inspirational fraction of oxygen could have a significant influence on treating lower PbtO2. Combined PbtO2 therapy, compared to the approach that focus only on regulation of cerebral perfusion pressure and intracranial pressure, shows better patient outcomes. Monitoring of PbtO2 could be helpful in individualizing treatment, preventing or limiting secondary brain injury, and maintaining better patient outcome. CASE DESCRIPTION: We present a case of a patient with subarachnoidal hemorrhage to whom PbtO2 monitor was implanted, and normobaric hyperoxia treatment was adjusted according to PbtO2 measurement. The patient progressively recovered and was dismissed with Glasgow Coma Score 4/5/6. CONCLUSION: The use of PbtO2 monitoring may be useful for monitoring the local tissue values that are useful for induction of normobaric hyperoxia and optimizing the therapy toward more target-defined values. It is an important part of multimodal neuromonitoring, and is the gold standard for brain oxygenation monitoring that can lead to better patient outcome.

Intraoperative Eptifibatide Administration During Urgent Arterial Bypass in Neurosurgery.

BACKGROUND: In some cases when risk of occlusion of a blood vessel is greater than risk of bleeding when patients undergo urgent or unplanned bypass during neurosurgery, the use of eptifibatide may be an option. We describe 2 patients who underwent arterial bypass in whom eptifibatide was used successfully intraoperatively during neurosurgery for prevention of bypass occlusion. CASE DESCRIPTION: The first patient presented with a right middle cerebral artery (MCA) aneurysm with subocclusive stenosis of the M1 branch. After right-sided osteoplastic frontotemporal craniotomy, the MCA bifurcation was exposed with a bifurcational 6-mm aneurysm with a wide neck. Prebifurcation stenosis was found, with yellow calcification of the vessel wall, and postbifurcation calcification was found on the upper M2 branch. Superficial temporal artery-MCA bypass and occlusion of the MCA aneurysm was done. Before the bypass, continuous intravenous infusion of eptifibatide 1 µg/kg/minute was administered. The patient recovered normally without hemorrhage or neurologic deficit. The second patient presented with a left-sided lateral sphenoid wing meningioma. Left-sided frontotemporal craniotomy was performed, and the tumor was completely removed from the arachnoid layer. The temporal M3 branch was invaded by the meningioma. As there was no flow through the invaded segment of the aforementioned artery, termino-terminal M3 arterial anastomosis was done. Continuous intravenous infusion of eptifibatide 1 µg/kg/minute was administered. Indocyanine green angiography showed normal flow through the anastomosis, and the patient recovered normally. CONCLUSIONS: Future studies are needed to test the safety and potential efficacy of eptifibatide in intraoperative settings.

West syndrome with periventricular leukomalacia: ten-year clinical study.

The aim of the study was to evaluate magnetic resonance imaging (MRI) findings in infants with periventricular leukomalacia (PVL) and West syndrome (WS) and determine the neurodevelopmental outcome in children with West syndrome and PVL. Ultrasound and brain MRI were performed in 37 infants with recognized PVL. PVL was categorized according to De Vries, whereas West syndrome was categorized according to International League Against Epilepsy 1989. West syndrome in our patients developed during the first 2 years of life. The most common interictal abnormality was hypsarrhythmia. All, except two patients had delayed development and various degrees of mental retardation. The most characteristic neuroimaging findings were major reduction in cerebral cortical gray matter volume, reduction in the volume of brain myelin, and delayed myelination. These findings may explain the anatomical association between the West syndrome onset and PVL and intellectual and cognitive deficit in premature infants with PVL.

Neurodevelopmental outcome in children with periventricular leukomalacia.

The purpose of this study was to question the correlation of different grades of periventricular leukomalacia (PVL) and subsequent neurodevelopmental outcome. In a prospective study we followed 52 preterm infants. Infants were divided into three groups according to their cranial ultrasound findings of PVL (De Vries classification). Seventeen children had PVL 1, 20 children had PVL 2, and 15 children had PVL 3. All 15 (100%) children with PVL 3 developed cerebral palsy with additional visual perceptual dysfunctions and epilepsy. Children with PVL 1 had high frequency of mild neuromotoric delay and visual impairment. PVL 2 and 3 have great predictive value for subsequent severe neurodevelopmental disorder which refers to cerebral palsy, different cognitive deficits, vision impairment and epilepsy. We have determined that due to high frequency of visual impairment and epilepsy we need to include neurophysiologic examinations very early in children with PVL lesions.