Bisphenol A Effects on Neurons' Neurochemical Character in the Urinary Bladder Intramural Ganglia of Domestic Pigs.

Bisphenol A (BPA), a substance globally used to produce plastics, is part of many everyday items, including bottles, food containers, electronic elements, and others. It may penetrate the environment and living organisms, negatively affecting, among others, the nervous, immune, endocrine, and cardiovascular systems. Knowledge of the impact of BPA on the urinary bladder is extremely scarce. This study investigated the influence of two doses of BPA (0.05 mg/kg body weight (b.w.)/day and 0.5 mg/kg b.w./day) given orally for 28 days on the neurons situated in the ganglia located in the urinary bladder trigone using the typical double immunofluorescence method. In the study, an increase in the percentage of neurons containing substance P (SP), galanin (GAL), a neuronal isoform of nitric oxide synthase (nNOS-used as the marker of nitrergic neurons), and/or cocaine- and amphetamine-regulated transcript (CART) peptide was noted after BPA administration. The severity of these changes depended on the dose of BPA and the type of neuronal factors studied. The most visible changes were noted in the cases of SP- and/or GAL-positive neurons after administering a higher dose of BPA. The results have shown that oral exposure to BPA, lasting even for a short time, affects the intramural neurons in the urinary bladder wall, and changes in the neurochemical characterisation of these neurons may be the first signs of BPA-induced pathological processes in this organ.

Bisphenol A affects vipergic nervous structures in the porcine urinary bladder trigone.

Bisphenol A (BPA) is used in the production of plastics approved for contact with feed and food. Upon entering living organisms, BPA, as a potent endocrine disruptor, negatively affects various internal organs and regulatory systems, especially in young individuals. Although previous studies have described the neurotoxic effects of BPA on various tissues, it should be underlined that the putative influence of this substance on the chemical architecture of the urinary bladder intrinsic innervation has not yet been studied. One of the most important neuronal substances involved in the regulation of urinary bladder functions is vasoactive intestinal polypeptide (VIP), which primarily participates in the regulation of muscular activity and blood flow. Therefore, this study aimed to determine the influence of various doses of BPA on the distribution pattern of VIP-positive neural structures located in the wall of the porcine urinary bladder trigone using the double-immunofluorescence method. The obtained results show that BPA influence leads to an increase in the number of both neurons and nerve fibres containing VIP in the porcine urinary bladder trigone. This may indicate that VIP participates in adaptive processes of the urinary bladder evoked by BPA.

A Novel Method of Vein Detection with the Use of Digital Image Correlation.

Digital image correlation may be useful in many different fields of science, one of which is medicine. In this paper, the authors present the results of research aimed at detecting skin micro-shifts caused by pulsation of the veins. A novel technique using digital image correlation (DIC) and filtering the resulting shifts map to detect pulsating veins was proposed. After applying the proposed method, the veins in the forearm were visualized. The proposed technique may be used in the diagnosis of venous stenosis and may also contribute to reducing the number of adverse events during blood collection. The great advantage of the proposed method is the lack of the need to have specialized equipment, only a typical mobile phone camera is needed to perform the test.

Cocaine- and amphetamine-regulated transcript (CART) peptide in the enteric nervous system of the porcine esophagus.

Cocaine- and amphetamine-regulated transcript peptide (CART) is widely distributed within the central and peripheral nervous system. In the brain, CART is considered as the main anorectic peptide involved in the regulation of food intake. Contrary to the central nervous system, a lot of aspects connected with the distribution and functions of CART within the enteric nervous system (ENS) still remain unknown. The aim of the present study was to investigate, for the first time, the population of CART-like immunoreactive (CART-LI) neurons within the porcine esophagus and the denotation of their neurochemical coding. During this experiment, the distribution of CART-LI neurons and the colocalization of CART with other neuronal active substances were examined using standard double- and triple-immunofluorescence techniques in enteric plexuses of cervical, thoracic, and abdominal esophagus fragments. The obtained results showed that CART is present in a relatively high percentage of esophageal neurons (values fluctuated from 45.2±0.9% in the submucous plexus of the thoracic esophagus to 58.1±5.0% in the myenteric plexus of the same fragment of the esophagus). Moreover, CART colocalized with a wide range of other active neuronal substances, mainly with the vesicular acetylcholine transporter (VAChT, a marker of cholinergic neurons), neuronal isoform of nitric oxide synthase (nNOS, a marker of nitrergic neurons), vasoactive intestinal polypeptide (VIP) and galanin (GAL). The number of CART-positive neuronal cells and their neurochemical coding clearly depended on the fragment of esophagus studied and the type of enteric plexus. The obtained results suggest that CART may play important and multidirectional roles in the neuronal regulation of esophageal functions.

Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial.

Aims: Inhalation of nitric oxide (iNO) during myocardial ischaemia and after reperfusion confers cardioprotection in preclinical studies via enhanced cyclic guanosine monophosphate (cGMP) signalling. We tested whether iNO reduces reperfusion injury in patients with ST-elevation myocardial infarction (STEMI; NCT01398384). Methods and results: We randomized in a double-blind, placebo-controlled study 250 STEMI patients to inhale oxygen with (iNO) or without (CON) 80 parts-per-million NO for 4 h following percutaneous revascularization. Primary efficacy endpoint was infarct size as a fraction of left ventricular (LV) size (IS/LVmass), assessed by delayed enhancement contrast magnetic resonance imaging (MRI). Pre-specified subgroup analysis included thrombolysis-in-myocardial-infarction flow in the infarct-related artery, troponin T levels on admission, duration of symptoms, location of culprit lesion, and intra-arterial nitroglycerine (NTG) use. Secondary efficacy endpoints included IS relative to risk area (IS/AAR), myocardial salvage index, LV functional recovery, and clinical events at 4 and 12 months. In the overall population, IS/LVmass at 48-72 h was 18.0 ± 13.4% in iNO (n = 109) and 19.4 ± 15.4% in CON [n = 116, effect size -1.524%, 95% confidence interval (95% CI) -5.28, 2.24; P = 0.427]. Subgroup analysis indicated consistency across clinical confounders of IS but significant treatment interaction with NTG (P = 0.0093) resulting in smaller IS/LVmass after iNO in NTG-naïve patients (n = 140, P < 0.05). The secondary endpoint IS/AAR was 53 ± 26% with iNO vs. 60 ± 26% in CON (effect size -6.8%, 95% CI -14.8, 1.3, P = 0.09) corresponding to a myocardial salvage index of 47 ± 26% vs. 40 ± 26%, respectively, P = 0.09. Cine-MRI showed similar LV volumes at 48-72 h, with a tendency towards smaller increases in end-systolic and end-diastolic volumes at 4 months in iNO (P = 0.048 and P = 0.06, respectively, n = 197). Inhalation of nitric oxide was safe and significantly increased cGMP plasma levels during 4 h reperfusion. The Kaplan-Meier analysis for the composite of death, recurrent ischaemia, stroke, or rehospitalizations showed a tendency toward lower event rates with iNO at 4 months and 1 year (log-rank test P = 0.10 and P = 0.06, respectively). Conclusions: Inhalation of NO at 80 ppm for 4 h in STEMI was safe but did not reduce infarct size relative to absolute LVmass at 48-72h. The observed functional recovery and clinical event rates at follow-up and possible interaction with nitroglycerine warrant further studies of iNO in STEMI.

Platelet activation and microvascular injury in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Dual antiplatelet therapy reduces the risk of thrombotic complications after primary percutaneous coronary intervention (PCI). AIM: To assess whether inhibition of platelet function attenuates microvascular damage in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We studied 83 STEMI patients treated with primary PCI. Platelet aggregation was measured on admission (ADM) and 4 days later (D4) by light transmission aggregometry after stimulation with 0.5 mM of arachidonic acid and after stimulation with 5 and 20 µM of adenosine diphosphate (ADP) on treatment with dual antiplatelet therapy with aspirin and clopidogrel. Platelet-neutrophil aggregate (PNA) and platelet-monocyte aggregate (PMA) were analysed by flow cytometry. Contrast-enhanced magnetic resonance imaging was performed 2-4 days after STEMI to detect the area of perfusion defect at rest and to determine the size of microvascular obstruction. Microvascular obstruction was expressed as a percentage of infarct area. RESULTS: Perfusion defect at rest was found in 56 (67.5%) patients whereas microvascular obstruction in 63 (75.9%) patients. Patients with perfusion defect at rest had on admission a significantly higher level of both PMA (7.0 vs. 4.5%, p = 0.004) and PNA (4.1 vs. 2.2%, p = 0.016), however there were no significant differences at D4. Platelet aggregation after stimulation with 5 µM of ADP on ADM was correlated (r = 0.37, p = 0.004) with microvascular obstruction area. Moreover, the higher the concentration of PMA(ADM) (r = 0.31, p = 0.016), PNA(ADM) (r = 0.34, p = 0.006) and PM(AD4) (r = 0.35, p = 0.005) the larger the size of microvascular obstruction. Infarct size (ß = 0.43, 95% CI 0.19 to 0.67, p 〈 0.0001), TIMI < 3 after PCI (ß = -0.27, 95% CI -1.90 to -0.11, p = 0.015) and PMA(D4) (ß = 0.21, 95% CI 0.13 to 1.86, p = 0.032) independently influenced the size of microvascular obstruction (R2 = 0.60, p 〈 0.0001). CONCLUSIONS: Excessive platelet activation during reperfusion in STEMI patients despite dual antiplatelet therapy is associated with greater microvascular impairment.

Effect of blood glucose levels on prognosis in acute myocardial infarction in patients with and without diabetes, undergoing percutaneous coronary intervention.

BACKGROUND: Diabetes mellitus (DM) is a significant factor regarding poor outcome in patients with myocardial infarction. Recently a new prognostic factor is under consideration - a baseline glucose level on admission. We sought to assess the influence of blood glucose levels on admission on prognosis of patients with acute ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients treated with PCI for STEMI were analyzed. Presence or absence of DM was the first grouping criterion. The secondary criterion was the blood glucose level on admission [threshold >or= 7.8 mmol/L (140 mg/dL)]. Hyperglycemic and non-hyperglycemic subgroups were selected within both DM and non-DM groups according to the threshold. One-year mortality of diabetics was 16.0%. There was no significant difference in 1-year mortality between hyperglycemic and non-hyperglycemic patients with DM. One-year mortality in the non-DM group was 5.6%. Patients without DM but with hyperglycemia showed a higher 1-year mortality rate than non-hyperglycemic patients (8.51% vs. 3.68%, p = 0.001). Multivariate analysis revealed that in the non-DM group blood glucose level (per 1 mmol/L) on admission was a factor affecting 1-year mortality [HR = 1.09 (1.01-1.17)]. CONCLUSIONS: Elevated blood glucose levels in STEMI affect the prognosis of patients without DM; however, it is not an independent death risk factor of patients with DM treated with PCI.

Does glucose level at hospital discharge predict one-year mortality in patients with diabetes mellitus treated with percutaneous coronary intervention for ST-segment elevation myocardial infarction?

BACKGROUND: It has been shown that diabetes mellitus (DM) is an independent prognostic factor in patients with myocardial infarction (MI). In addition to that fact the prognostic significance of blood glucose (BG) abnormalities in the acute phase of MI has also been suggested. Recently, a new prognostic factor has been evaluated - the glucose level at hospital discharge. AIM: To assess whether the glucose level at hospital discharge is associated with one-year mortality in patients with DM treated with percutaneous coronary intervention (PCI) for ST-segment elevation MI (STEMI), taking into account hypoglycaemic treatment. METHODS: Consecutive patients with STEMI and DM treated with PCI, who survived hospitalisation, were included in the analysis. Patients were assumed to have DM if previous diagnosis of DM or newly diagnosed DM during hospital stay was noted. Criteria of newly diagnosed DM were as follows: fasting BG >or=7 mmol/l at least twice after acute phase of STEMI, BG >or=11.1 mmol/l in a 2-hour glucose tolerance test performed before discharge. Fasting plasma glucose at hospital discharge was used for analysis. RESULTS: Out of 2762 consecutive patients with STEMI, 565 had DM. In-hospital mortality in this group was 9.4% (53 patients), so the final DM group consisted of 512 patients. After discharge 59 (11.5%) patients died during one-year follow-up. The glucose level at discharge was not an independent prognostic factor of one-year mortality in the whole analysed group, however insulin treatment at discharge was (HR 2.61, 95% CI 1.29-5.29; p=0.008). Afterwards, we undertook multivariate analysis separately in the group treated with insulin (253 patients) and in the group treated with oral drugs or diet only (259 patients). This analysis showed that in the group treated with insulin the glucose level at discharge was not an independent prognostic factor of one-year mortality (HR 1.07, 95% CI 0.95-1.22; p=0.27), whereas in patients treated with hypoglycaemic agents or diet it was significantly associated with a one-year mortality (HR 1.30, 95% CI 1.01-1.68; p=0.049). CONCLUSIONS: 1. Patients with STEMI and DM treated with insulin at hospital discharge have higher risk of death, probably because of more advanced DM and more severe complications, than patients treated with oral drugs or diet. 2. Elevated glucose level at hospital discharge predict one-year mortality only in patients with MI and DM treated with oral drugs or diet.

Relationship between blood glucose on admission and prognosis in patients with acute myocardial infarction treated with percutaneous coronary intervention.

BACKGROUND: Diabetes mellitus in patients with myocardial infarction affects in-hospital and late mortality. It has been shown that the glucose level on admission can also affect prognosis. This conclusion was based on an analysis performed on a heterogeneous group of patients, treated not only with percutaneous coronary intervention (PCI) but also with fibrinolysis. Moreover, the threshold values hyperglycaemia for the diagnosis of were also variable. AIM: To assess whether glucose level on admission affects in-hospital and one-year prognosis in patients with ST-segment elevation myocardial infarction (STEMI) treated with PCI. METHODS: Consecutive patients with STEMI treated with PCI were included in the analysis. Patients with STEMI complicated by cardiogenic shock were also included. Three groups according to the glucose level on admission were analysed: group I - <7.8 mmol/l (140 mg/dl), group II - 7.8-11.1 mmol/l (140-200 mg/dl), and group III - > or = 11.1 mmol/l (200 mg/dl). RESULTS: The incidence of diabetes mellitus in the total group (1027 patients) was 26.1%, and of cardiogenic shock - 9.2%. Group I consisted of 472 patients, group II - 307 patients, and group III - 248 patients. Compared with normoglycaemic patients, those with elevated glucose level were older, more often female, had more often hypertension, diabetes mellitus, cardiogenic shock, were more often treated with fibrinolysis before PCI but were less often smokers. Multivessel disease and initial patency of the infarct-related artery (TIMI 0-1) were more often observed in patients with higher glucose level. A trend towards a higher incidence of reocclusion was also more often present in patients with increased glucose level. Moreover, mean creatine kinase concentration was the highest and the left ventricular ejection fraction was the lowest in group III. During the in-hospital stay, the complication rate was as follows: stroke (1.1% vs. 1.3% vs. 4.4%), and mortality (2.8 vs. 4.9 vs. 13.3%) in groups I, II, and III, respectively. The same tendency was observed during the one-year follow-up period: stroke (1.3 vs. 2.9 vs. 6.9%), mortality (6.4 vs. 9.1 vs. 22.6%). The 1 mmol/l (18 mg/dl) increase of the baseline glucose level among various risk factors was an independent prognostic factor of higher -year mortality (HR=1.06; 95% CI 1.02-1.09). Diabetes mellitus did not affect prognosis among patients included in the analysis. CONCLUSION: Elevated glucose level on admission is associated with adverse prognosis in patients with STEMI treated with PCI.