Effects of Transendocardial Delivery of Bone Marrow-Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.

RATIONALE: New therapies for refractory angina are needed. OBJECTIVE: Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina. METHODS AND RESULTS: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: -1.38 [5.2] versus -0.73 [1.9], P=0.65; and total perfusion deficit: -1.33 [3.3] versus -2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: -9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months. CONCLUSION: Transendocardial CD133+ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.

Effects of electrospun scaffolds of di-O-butyrylchitin and poly-(ε-caprolactone) on wound healing.

BACKGROUND: We sought to determine the usefulness of electrospun dibutyrylchitin (DBC) or poly-(ε-caprolactone [PCL]), in wound treatment. We investigated the mechanisms of action of these polymers on wound healing. METHODS: We synthesized DBC, a newly identified ester derivative of chitin, using a patented method comprising the substitution of butyryl groups at positions C-3 and C-6 in chitin molecules. We confirmed the double substitution by the butyric groups using infrared spectrometry. The fibrous scaffolds were obtained using the electrospinning method. A polypropylene net was implanted subcutaneously in the rat and served as a wound model. RESULTS: Both DBC and PCL increased granulation tissue weight in the wound. In contrast to PCL, DBC did not abolish glycosaminoglycan changes in wounds. The tested samples did not impair total collagen synthesis or induce excessive fibrosis. In both PCL- and DBC-treated wounds, we observed a lower level of soluble collagen (compared with controls). The results show better hydration of the wounds in both the DBC and PCL groups. No induction of large edema formation by the tested materials was observed. These polymers induced almost identical macrophage-mediated reactions to foreign-body implantation. The implants increased the blood vessel number in a wound. CONCLUSION: Both PCL and DBC could be used as scaffolds or dressings for wound treatment. The materials were safe and well tolerated by animals. As DBC did not disturb glycosaminoglycan accumulation in wounds and absorbed twice as much liquid as PCL, it can be considered superior.

CONTEXTE: Nous avons cherché à déterminer l'utilité du dibutyryl-chitine (DBC) ou du poly-(ε-caprolactone [PCL]) électrofilés dans le traitement des plaies. Nous avons étudié les mécanismes d'action de ces polymères sur la cicatrisation des plaies. MÉTHODES: Nous avons synthétisé le DBC, un dérivé ester récemment identifié de la chitine, à l'aide d'une méthode brevetée incluant la substitution des groupes butyryl aux positions C-3 et C-6 des molécules de chitine. Nous avons confirmé la substitution double par les groupes butyriques à l'aide de la spectrométrie infrarouge. Les échafaudages fibreux ont été obtenus grâce à la méthode de filage électrostatique. Un filet en polypropylène a été implanté par voie sous-cutanée dans le rat et a servi de modèle de plaie. RÉSULTATS: Le DBC et le PCL ont tous deux augmenté le poids du tissu de granulation dans la plaie. Contrairement au PCL, le DBC n'a pas supprimé les changements des glycosaminoglycanes des plaies. Les échantillons examinés n'ont pas perturbé la synthèse totale de collagène ni entraîné une fibrose excessive. Nous avons observé un niveau inférieur de collagène soluble (par rapport aux témoins) tant dans les plaies traitées par PCL que par DBC. Les résultats montrent une amélioration de l'hydratation des plaies tant pour les groupes DBC que PCL. Les matériaux à l'étude n'induisaient pas d'œdème étendu. Ces polymères ont induit des réactions macrophagiques presque identiques à l'implantation d'un corps étranger. Les implants ont accru le nombre de vaisseaux sanguins de la plaie. CONCLUSION: Tant le PCL que le DBC pourraient être utilisés comme échafaudages ou pansements pour le traitement des plaies. Les matériaux étaient sécuritaires et ont été bien tolérés par les animaux. Comme le DBC n'a pas perturbé l'accumulation des glycosaminoglycanes des plaies et a absorbé 2 fois plus de liquide que le PCL, il peut être considéré comme étant supérieur.

[Galanin-like peptide (GALP): localization, receptors and biological function]. / Peptyd galaninopodobny (GALP): wystepowanie, receptory i funkcja biologiczna.

Galanin-like peptide (GALP) was isolated from porcine hypothalamus in 1999 on the basis of its ability to activate galanin receptors in vitro. Extensive studies carried out since the discovery of GALP contributed to the significant progress in our knowledge regarding this neuropeptide. GALP is synthesized mainly in the neurons of the hypothalamic arcuate nucleus and in the pituicytes of the posterior pituitary. The effects of GALP are mediated by well-characterized G-protein coupled galanin receptor subtypes. The fact that GALP shares homology only with 13 amino acids of the galanin sequence suggests that it might also interact with its own specific receptor. This relatively small 60-amino acid peptide belongs to a growing list of neuropeptides that play a crucial role in the regulation of food intake, energy balance and the reproductive axis. This peptide appears to be involved in integrating energy balance control and reproduction. The paper presents the current state of knowledge about the biosynthesis, structure, localization of GALP and its receptors, with particular emphasis on its role. This review will attempt to summarize the significant body of in vitro and in vivo studies conducted so far, concerning the effects of GALP.

The role of external iliac artery diameter indexed to BSA score in predicting vascular access complications after transfemoral transcatheter aortic valve implantation.

Introduction: Aortic stenosis is the most common primary valve disease and requires invasive treatment. Transcatheter aortic valve implantation (TAVI) from a transfemoral access is a routine intervention worldwide. Aim: To investigate the correlation between external iliac artery diameter (EIAD) indexed to body surface area (BSA) (EIAD-BSA) and access site complications in patients undergoing TAVI via transfemoral access (TF) (TF-TAVI). Material and methods: Patients underwent TF-TAVI in 2017-2019 at the Upper-Silesian Medical Center in Katowice. Based on the preoperative multi-slice computed tomography (MSCT), pre-specified measurements of the ilio-femoral vessels were performed. The results were indexed to BSA and body mass index (BMI). Complications after TAVI were defined by Valve Academic Research Consortium 3 (VARC-3). The primary outcome regarding the adverse events after TAVI was the composite of access site complications requiring surgical intervention or blood transfusion. Results: The registry included 193 unselected patients with severe symptomatic aortic stenosis. Vascular and access-related complications including bleeding occurred in 17.1% of patients. Major TAVI access site complications (VARC-3) were reported in 5.7% of patients, while minor complications (VARC-3) occurred in 2.6%. EIAD-BSA demonstrated a positive correlation with the access site complications primary endpoint. Patients with greater EIAD-BSA had a numerically higher number of access site adverse events requiring surgical intervention or blood transfusion: n = 12 (5%) vs. n = 4 (4%), p = 0.011. Conclusions: External iliac artery diameter indexed to BSA could be an underestimated indicator of unfavorable outcomes after TF-TAVI, predicting periprocedural access site complications.

Outcome comparison of different approaches to aortic root aneurysm.

BACKGROUND: The treatment of aortic root aneurysm remains challenging for both cardiac surgeons and cardiologists. AIMS: This study aimed to assess and compare the long-term outcomes of different approaches to aortic root replacement (ARR). METHODS: All elective patients operated for aortic root aneurysm with or without aortic regurgitation at our institution over a 10-year period were included. We excluded patients with any degree of aortic stenosis and with active endocarditis. We assessed mortality, freedom from reoperation, freedom from aortic valve regurgitation, and the rate of hemorrhagic and thromboembolic complications. RESULTS: Two hundred and four patients underwent elective aortic root replacement: 107 (53%) valve-sparing aortic root replacement (VSARR), 35 (17%) mechanical Bentall procedure (MB), and 62 (30%) Bio-Bentall procedure (BB). Early mortality for VSARR, BB, and MB group was 2.8%, 4.8%, and 0%, respectively (P = 0.40). Estimated 5-year survival was: 90.2% vs. 78.4% vs. 94.2%, respectively (P = 0.12), 5-year freedom from reoperation: 97.8%, 96.6%, and 96.8%, respectively (P = 0.99). Estimat-ed 5-year freedom from complications was: 94.2%, 83.1% and 57.3% in the VSARR, BB and MB group, respectively (P <0.001). On last follow-up echocardiography, 90.5%, 98.4%, and 97.1% (P = 0.08) of patients were free from aortic regurgitation grade 2 or higher. The median (IQR) aortic valve peak gradient was 9 (6-12) mm Hg, 12 (10-18) mm Hg and 16 (14-22) mm Hg, respectively (P <0.001). Complications were predicted by mechanical Bentall (hazard ratio, 6.70 [2.54-17.63]; P <0.001). CONCLUSION: With the same mortality, freedom from reoperation, and a minimal late complication rate in comparison with mechanical Bentall and Bio-Bentall, VSARR might be the preferred approach to aortic root aneurysm.

New Indomalayan Nebularmis species (Heterotardigrada: Echiniscidae) provoke a discussion on its intrageneric diversity.

Recent years have brought undeniable progress in tardigrade taxonomy, and speciose complexes were detected in a number of phylogenetic lineages. The family Echiniscidae is one such lineage; it is one of the most diverse groups of limno-terrestrial tardigrades and can be characterized as having achieved great evolutionary success. In this contribution, using populations representing several species that originated from the Indomalayan region, we reconstructed phylogenetic affinities within Nebularmis, a recently erected genus within the Echiniscus lineage. Nebularmis auratus sp. nov. and Nebularmis burmensis sp. nov. are described from the Eastern Yoma Mountains and the Shan Hills (Myanmar), Nebularmis bhutanensis sp. nov. is described from the Eastern Himalayas (Bhutan), and Nebularmis indicus sp. nov. is described from the foothills of the Western Ghats (Goa, India). Moreover, males are reported in populations of the last two species. All known members of the genus can be phenotypically differentiated based on minute details of their dorsal sculpture and claws. Moreover, a very wide tropical distribution is demonstrated for Nebularmis cirinoi, recorded for the first time from islands of the Malay Archipelago. Furthemore, novel morphological, genetic, and geographic data allowed for the clarification of the generic diagnosis. Currently available data favor a scenario under which Nebularmis evolved in Southeast Asia and later dispersed to other regions of the globe.

Comparison of bicuspid and tricuspid aortic valve repair.

OBJECTIVES: The aim of this study was to compare the outcomes of tricuspid aortic valve (TAV) and bicuspid aortic valve (BAV) repair. METHODS: We assessed mortality, freedom from reoperation and the rate of aortic valve regurgitation recurrence. Mortality in both groups was compared with expected survival, and risk factors for reoperation were identified. RESULTS: From January 2010 to April 2020, a total of 368 elective aortic valve repair procedures were performed, including 223 (60.6%) in patients with TAV. The perioperative mortality was 0.7% in the BAV group and 3.6% in the TAV group (P = 0.079). Estimated survival at 5 years in the BAV versus TAV group was 97 ± 3% vs 80 ± 6%, respectively (P < 0.001). Freedom from reoperation at 5 years in the TAV versus BAV group was 96 ± 3% vs 93 ± 4%, respectively (P = 0.28). Grade 2 or more aortic valve regurgitation was noted in 9.9% of BAV patients and 11% of TAV patients (P = 0.66). Reoperation was predicted by cusp perforation [hazard ratio 15.86 (4.44-56.61); P < 0.001], the use of pericardial patch [hazard ratio 8.58 (1.96-37.53); P = 0.004] and aortic valve annulus diameter >27.5 mm [hazard ratio 3.07 (0.99-9.58); P = 0.053]. CONCLUSIONS: BAV repair is as durable as TAV repair. BAV is not a predictor of a higher rate of reoperations. BAV repair yields survival comparable to expected. Cusp perforation, aortic valve annulus diameter >27.5 mm and the use of pericardial patch adversely impact long-term outcome of aortic valve repair.

Short-term safety and efficacy of transcarotid transcatheter aortic valve implantation with balloon-expandable vs. self-expandable valves.

INTRODUCTION: Transfemoral access (TF) is the preferred access for transcatheter aortic valve implantation (TAVI). Transcarotid TAVI (TC-TAVI) is an alternative for patients in whom TF-TAVI is impossible. Two types of valves - balloon-expandable (BE) and self-expandable (SE) - can be used in TC-TAVI procedures. AIM: Comparison of the short-term results of patients treated with TC-TAVI using BE and SE valves. MATERIAL AND METHODS: The retrospective registry included 39 patients in whom the TC-TAVI procedure was performed between 2017 and 2020 (BE-TAVI; n = 10, SE-TAVI; n = 29). Preoperative characteristics, operative and postoperative results, and 30-days mortality were compared. RESULTS: Patients from the BE-TAVI group had higher surgical risk (EuroSCORE) (10.8% (6.2-14.0) vs. 5.5% (4.3-8.7); p = 0.027). The incidence of chronic obstructive pulmonary disease (COPD) was higher in the SE-TAVI group (34.5% vs. 0%; p = 0.040). In terms of other comorbidities, demographics, preprocedural laboratory results, transthoracic echocardiography (TTE), and multislice computed tomography (MSCT), the two groups were comparable. In both groups, we observed 100% procedural success. The median valve size was larger in the SE-TAVI group (29.0 (26.0-29.0) vs. 26.0 (23.0-26.0); p < 0.001). The hospitalization time was shorter in the BE-TAVI group vs. SE-TAVI (5.8 ±0.6 vs. 6.4 ±0.9; p = 0.043). We did not observe statistically significant differences between BE-TAVI and SE-TAVI in periprocedural and 30-day mortality, or the number of strokes/TIA. Also TTE parameters and NYHA class showed similar improvement at 30 days in both groups. CONCLUSIONS: TC-TAVI using balloon-expandable and self-expandable valves showed similar safety and efficacy in 30 days follow-up.

Long-Term Clinical Outcomes and Carotid Ultrasound Follow-Up of Transcarotid TAVI. Prospective Single-Center Registry.

This study aimed to prospectively evaluate the safety and long-term clinical outcomes of cerebral-oximetry-guided transcarotid transcatheter aortic valve implantation (TC-TAVI) with systematic follow-up with carotid ultrasound. Thirty-three TCTAVI procedures were performed in our center from 2017 to 2019. Our analysis includes in-hospital outcomes and long-term follow-up data on mortality, echocardiographic parameters, carotid Doppler ultrasound, and VARC-2 defined clinical events. Intraoperatively, one patient died, and one had a transient ischemic attack (TIA). The following events occurred in-hospital postoperatively: myocardial infarction (3.0%), cardiac tamponade (3.0%), new-onset atrial fibrillation (6.3%), need for temporary pacing (27.3%) and need for pacemaker implantation (15%). The mean follow-up was 19.5 ± 9.52 months. In the long-term follow-up, the two-year survival rate was 83% ± 14. The echocardiographic parameters did not differ significantly from the postprocedural values, and the ultrasound did not show any cases of significant vessel narrowing. The mean peak systolic velocity (PSV) was 71.6 cm/s in the left common carotid artery and 70.6 cm/s in the right common carotid artery. In conclusion, cerebral oximetry-guided TC access is safe, has a favorable long-term outcome, and does not increase the risk of plaque formation in the carotid artery. In a carefully selected group of patients, it might be considered as a first-choice alternative to TF access.

Comparison of the short-term safety and efficacy of transcarotid and transfemoral access routes for transcatheter aortic valve implantation.

BACKGROUND: Transfemoral access is the preferred approach for transcatheter aortic valve implantation (TAVI), as it is characterized by the lowest complication rate. In the majority of patients ineligible for transfemoral access, the transcarotid approach can be used. AIMS: This study aimed to compare short­term outcomes in 2 groups of patients treated with transcarotid or transfemoral TAVI. METHODS: A retrospective comparison included 265 patients in whom the TAVI procedure was performed between 2017 and 2019 (transcarotid TAVI, n = 33; transfemoral TAVI, n = 232). Preoperative characteristics, procedural and postprocedural outcomes, as well as 30­day mortality were assessed. RESULTS: Compared with the transfemoral TAVI group,patients undergoing transcarotid TAVI presented with a higher New York Heart Association (NYHA) functional class (median [interquartile range (IQR)], 3 [3-3] vs 2 [2-3]; P <0.001), a higher surgical risk (median [IQR] EuroSCORE II, 6 [4.8-10.7] vs 4.8 [2.8-7.9]; P = 0.003), and a higher incidence of peripheral artery disease (36.4% vs 18.1%; P = 0.035). The median (IQR) procedure duration in the transcarotid TAVI group was shorter than in patients undergoing transfemoral TAVI (65 [60-80] min vs 90 [80-110] min; P <0.001, respectively). In both study groups, we noted a high percentage of procedural success (transcarotid vs transfemoral TAVI, 96.9% vs 97.2%; P = 0.66). We found no significant differences between transcarotid TAVI and transfemoral TAVI in terms of periprocedural and 30­day mortality as well as the number of strokes. Regardless of the access route chosen, echocardiographic parameters and the NYHA class similarly improved compared with preprocedural data. CONCLUSIONS: Despite posing a higher baseline risk and presenting a greater anatomic complexity, transcarotid access is safe and associated with 30­day outcomes similar to those observed for transfemoral access. Importantly, procedural time was short and no periprocedural strokes or vascular complications were reported.

Long-term outcomes of aortic valve repair in over 500 consecutive patients: a single-center experience.

BACKGROUND: Over the last years, aortic valve repair has evolved from being a random and irreproducible procedure to a standardized technique yielding durable long­term results. AIMS: The aim of the study was to assess long­term outcomes of aortic valve repair and aortic valve sparing procedures. METHODS: We analyzed the outcomes of all consecutive patients who underwent aortic valve repair and/ or aortic valve sparing root replacement till the end of 2019. We assessed mortality, freedom from reoperation, and freedom from at least moderate aortic valve regurgitation. RESULTS: A total of 504 patients underwent aortic valve repair and/or aortic valve sparing root replacement over 17 years, including 452 (89.7%) elective and 52 (10.3%) emergency surgeries for acute type A aortic dissections. Median (interquartile range) age was 59 (35-66) years, 72.4% were male. Median follow­up time was 35 months. Estimated 5­year survival was 83%, and 10­year survival was 73%. In 452 patients after elective surgery, the estimated actuarial 5­year and 10­year survival was 86% and 75%, respectively. In patients after emergency surgery for acute type A aortic dissection, actuarial 5­year survival was 62%, and 10­year survival was 62%. Estimated 5- and 10­year freedom from reoperation was 96% and 87%, respectively. The comparison of both subgroups did not reveal differences (P = 0.42). Freedom from at least moderate aortic valve regurgitation was confirmed in 86.6% of patients. CONCLUSIONS: Aortic valve repair is a durable and effective surgical procedure associated with low early and late mortality. Aortic valve reconstruction in patients with acute type A aortic dissection yields good long­term results.

Prospective registry on cerebral oximetry-guided transcarotid TAVI in patients with moderate-high risk aortic stenosis.

BACKGROUND: The aim of the study was to assess safety TAVI procedure through the common carotid artery in high-vascular-risk patients. METHODS: The approach was selected by a multidisciplinary (cardiologists and cardiac surgeons) heart team after analyzing preoperative coronary angiography, transthoracic echocardiography and multislice contrast computed tomography of the peripheral arteries. Patients with the following conditions were qualified to the transcarotid access: severe peripheral artery disease (stenotic, heavily calcified), tortuous or small diameter <6 mm iliofemoral arteries, descending and abdominal aortic disease. RESULTS: Ten transcarotid transcatheter aortic valve implantation procedures were performed in our hospital from September 2017 to May 2018. There were no in-hospital deaths or strokes. The procedural success rate defined as the implantation of the valve with no coronary obstruction and less than moderate paravalvular leak was 100%. Parameters of regional cerebral oximetry were symmetrical on the left and right side in all cases and only during rapid ventricular pacing transiently decreased below the value of 50%. Postoperative cerebrovascular complications and myocardial infarctions were not observed. Statistically significant reduction of the echocardiographic parameters (PGmax and PGmean, Vmax) were observed. Mild paravalvular leaks occurred in 4 patients. Additionally, the heart failure symptoms diminished after the procedure from a median class III to class II. In the 3-month follow-up, mortality is 10% (unknown cause of death of one patient). The mean NYHA class of the other patients is II. Echocardiographic parameters are comparable to postoperative day 4. CONCLUSIONS: The pilot registry showed the safety of transcarotid approach in patients with the anatomy precluding the transfemoral approach.

Effects of trans-endocardial delivery of bone marrow-derived CD133+ cells on angina and quality of life in patients with refractory angina: A sub-analysis of the REGENT-VSEL trial.

BACKGROUND: The REGENT-VSEL trial demonstrated a neutral effect of transendocardial injection of autologous bone marrow (BM)-derived CD133+ in regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial aims to assess the effect stem cell therapy has on quality of life (QoL) in patients with refractory angina. METHODS: Thirty-one patients (63.0 ± 6.4 years, 70% male) with recurrent CCS II-IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly assigned to the active stem cell group and 15 individuals were randomly assigned to the placebo group on a 1:1 basis. The inducibility of ischemia, (≥ one myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was measured using the Seattle Angina Questionnaire. Each patient completed the questionnaire prior to treatment and at the time of their outpatient follow-up visits at 1, 4, 6, and 12 months after cell/placebo treatment. RESULTS: The main finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in QoL in comparison to the control group. Moreover, there was no significant difference between cell therapy and placebo in a number of patients showing improvement of at least 1 Canadian Cardiovascular Society class during the follow-up period. CONCLUSIONS: Intra-myocardial delivery of autologous CD133+ stem cells is safe and feasible but does not show a significant improvement in the QoL or angina pectoris symptoms in patients with chronic myocardial ischemia.

[Influence of thyroliberin on vasopressin and oxytocin release from the hypothalamo-neurohypophysial system under in vivo and in vitro conditions]. / Wplyw tyreoliberyny na uwalnianie wazopresyny i oksytocyny z ukladu podwzgórzowo-przysadkowego w warunkach in vivo oraz in vitro.

A thorough presentation of the influence of thyroliberin (TRH) on vasopressin and oxytocin release from the hypothalamo-neurohypophysial system is presented. Thyroliberin affects in different ways both neurohormone secretion in females during lactation according to the water-electrolyte metabolism in the course of the circadian rhythm of vasopressin and oxytocin release as well as during in vitro incubation of isolated neurointermediate lobe or hypothalamo-neurohypohysial explants. The results showed that: TRH acts as a stimulator of oxytocin release into the blood by equilibrated water-electrolyte metabolism, TRH acts in the central nervous system as an inhibitory neuromodulator of vasopressin and oxytocin release from the hypothalamo-neurohypophysial system under in vitro conditions, by osmotic stimulation, as well as in females during lactation, TRH inhibits AVP release in acute bleeding-provoked hypovolemia and alters the circadian rhythm of vasopressin and oxytocin release. It is assumed that this neuropeptide can interact with the mechanisms engaged in vasopressin and oxytocin release and can disturb these mechanisms, especially under conditions of augmented demand of the organism for these neurohormones.

The role of histamine in the regulation of the viability, proliferation and transforming growth factor ß1 secretion of rat wound fibroblasts.

BACKGROUND: Inflammation mediators play a regulatory role in repair processes. The study will examine the influence of histamine on wound fibroblast metabolic activity, viability, proliferation, and TGFß1 secretion. The study also will identify the histamine receptor involved in regulation of the tested repair processes. METHODS: Fibroblasts were obtained from the granulation tissue of wounds or intact dermis of rats. The MTT and BrdU assays were used to examine the effect of histamine (10-8M-10-4M) on the viability and metabolic activity of fibroblasts, and on their proliferative capacity. The influence of histamine receptor antagonists (i.e., ketotifen, ranitidine, ciproxifan and JNJ7777120) and agonists (2-pyridylethlamine dihydrochloride, amthamine dihydrobromide) was also investigated. The TGFß1 and histamine receptors H1 were evaluated by enzyme-linked immunosorbent assay. RESULTS: Histamine significantly increased granulation tissue fibroblast viability and metabolic activity at 10-8 and 10-6M but did not change their proliferative activity. Only the blockade of the H1 receptor removed this effect of histamine. H1 receptor agonist (2-pyridylethlamine dihydrochloride) increased cell viability, thereby mimicking histamine action. Both Histamine (10-4M) and 2-pyridylethlamine dihydrochloride increased TGFß1 concentration in cell culture medium. However, ketotifen blocked histamine-induced augmentation of TGFß1. H1 receptor expression on wound fibroblasts was confirmed. CONCLUSION: The regulatory influence of histamine on wound fibroblast function (viability/metabolic activity or secretion of TGFß1) is dependent on H1 receptor stimulation. Contrary to wound fibroblasts, these cells express a very low level of H1 receptors when isolated from intact dermis and histamine is unable to modify their metabolic activity.

Can We Selectively Reduce Appetite for Energy-Dense Foods? An Overview of Pharmacological Strategies for Modification of Food Preference Behavior.

Excessive intake of food, especially palatable and energy-dense carbohydrates and fats, is largely responsible for the growing incidence of obesity worldwide. Although there are a number of candidate antiobesity drugs, only a few of them have been proven able to inhibit appetite for palatable foods without the concurrent reduction in regular food consumption. In this review, we discuss the interrelationships between homeostatic and hedonic food intake control mechanisms in promoting overeating with palatable foods and assess the potential usefulness of systemically administered pharmaceuticals that impinge on the endogenous cannabinoid, opioid, aminergic, cholinergic, and peptidergic systems in the modification of food preference behavior. Also, certain dietary supplements with the potency to reduce specifically palatable food intake are presented. Based on human and animal studies, we indicate the most promising therapies and agents that influence the effectiveness of appetite-modifying drugs. It should be stressed, however, that most of the data included in our review come from preclinical studies; therefore, further investigations aimed at confirming the effectiveness and safety of the aforementioned medications in the treatment of obese humans are necessary.

[The role of the connective tissue in healing process in myocardial infarction]. / Udzial tkanki lacznej w gojeniu zawalu serca.

Myocardial infarction is followed by the inflammatory response of mezenchymal tissue leading to the debridement of the necrotic area as well as to initiation of repair followed by scar formation. The healing is a complex sequence of events consisted of four overlapping phases. Repair of the heart is under control of local and systemic regulatory factors. The knowledge of the mechanism of myocardial infarction allows to develop new strategies aimed at minimizing necrotic area and optimizing cardiac repair. This approach gives a chance to reduce the complications of myocardial infarction and to improve the quality of patients life.

Invasive treatment of coronary artery disease in octogenarians.

INTRODUCTION: There are many patients aged over 80 years among those hospitalised for coronary artery disease (CAD). The unanswered question is whether invasive treatment of such patients is effective and safe. AIM: To assess and compare one-year clinical outcomes after percutaneous coronary angioplasty (PTCA) and surgical coronary artery bypass grafting (CABG) in patients aged over 80 years and in younger patients. METHOD: There were 63 patients aged over 80 years suffering from CAD who underwent either PTCA or CABG. The control group consisted of 40 patients aged 60-65 years treated in the same way. Data on medical history, cardiovascular risk factors, and angiographic findings were analysed. The potential risks of the procedures, post-procedural complications as well as the clinical status at the end of one-year follow-up were evaluated. RESULTS: There were 24 surgical revascularisation procedures and 39 PCIs performed in the very old patients. Stable angina was found in 29 cases, unstable angina in 19 and acute myocardial infarction in 15 patients. There were three in-hospital deaths and 18 periprocedural complications were noted. During the one-year follow-up period six deaths occurred, persistent or recurrent angina was found in 11 patients after PCI and two after CABG. There were no deaths in the control group and the incidence of minor complications was similar to the senile group. In younger patients who underwent CABG, CCS class at one year was lower than in the very old ones. CONCLUSIONS: The invasive treatment of coronary artery disease in octogenarians is feasible with satisfactory results and acceptable procedural risks.

Galanin and galanin-like peptide modulate vasopressin and oxytocin release in vitro: the role of galanin receptors.

Galanin (Gal) and galanin-like peptide (GALP) may be involved in the mechanisms of the hypothalamo-neurohypophysial system. The aim of the present in vitro study was to compare the influence of Gal and GALP on vasopressin (AVP) and oxytocin (OT) release from isolated rat neurohypophysis (NH) or hypothalamo-neurohypophysial explants (Hth-NH). The effect of Gal/GALP on AVP/OT secretion was also studied in the presence of galantide, the non-selective galanin receptors antagonist. Gal at concentrations of 10(-10 )M and 10(-8 )M distinctly inhibited basal and K(+)-stimulated AVP release from the NH and Hth-NH explants, whereas Gal exerted a similar action on OT release only during basal incubation. Gal added to the incubation medium in the presence of galantide did not exert any action on the secretion of either neurohormone from NH and Hth-NH explants. GALP (10(-10 )M and 10(-9 )M) induced intensified basal AVP release from the NH and Hth-NH complex as well as the release of potassium-evoked AVP from the Hth-NH. The same effect of GALP has been observed in the presence of galantide. GALP added to basal incubation medium was the reason for stimulated OT release from the NH as well as from the Hth-NH explants. However, under potassium-stimulated conditions, OT release from the NH and Hth-NH complexes has been observed to be distinctly impaired. Galantide did not block this inhibitory effect of GALP on OT secretion. It may be concluded that: (i) Gal as well as GALP modulate AVP and OT release at every level of the hypothalamo-neurohypophysial system; (ii) Gal acts in the rat central nervous system as the inhibitory neuromodulator for AVP and OT release via its galanin receptors; (iii) the stimulatory effect of GALP on AVP and OT release is likely to be mediated via an unidentified specific GALP receptor(s).