You took the words right out of my mouth: Dual-fMRI reveals intra- and inter-personal neural processes supporting verbal interaction.

Verbal communication relies heavily upon mutual understanding, or common ground. Inferring the intentional states of our interaction partners is crucial in achieving this, and social neuroscience has begun elucidating the intra- and inter-personal neural processes supporting such inferences. Typically, however, neuroscientific paradigms lack the reciprocal to-and-fro characteristic of social communication, offering little insight into the way these processes operate online during real-world interaction. In the present study, we overcame this by developing a "hyperscanning" paradigm in which pairs of interactants could communicate verbally with one another in a joint-action task whilst both undergoing functional magnetic resonance imaging simultaneously. Successful performance on this task required both interlocutors to predict their partner's upcoming utterance in order to converge on the same word as each other over recursive exchanges, based only on one another's prior verbal expressions. By applying various levels of analysis to behavioural and neuroimaging data acquired from 20 dyads, three principal findings emerged: First, interlocutors converged frequently within the same semantic space, suggesting that mutual understanding had been established. Second, assessing the brain responses of each interlocutor as they planned their upcoming utterances on the basis of their co-player's previous word revealed the engagement of the temporo-parietal junctional (TPJ), precuneus and dorso-lateral pre-frontal cortex. Moreover, responses in the precuneus were modulated positively by the degree of semantic convergence achieved on each round. Second, effective connectivity among these regions indicates the crucial role of the right TPJ in this process, consistent with the Nexus model. Third, neural signals within certain nodes of this network became aligned between interacting interlocutors. We suggest this reflects an interpersonal neural process through which interactants infer and align to one another's intentional states whilst they establish a common ground.

Cognitive Aftereffects of Acute tDCS Coupled with Cognitive Training: An fMRI Study in Healthy Seniors.

Enhancing cognitive functions through noninvasive brain stimulation is of enormous public interest, particularly for the aging population in whom processes such as working memory are known to decline. In a randomized double-blind crossover study, we investigated the acute behavioral and neural aftereffects of bifrontal and frontoparietal transcranial direct current stimulation (tDCS) combined with visual working memory (VWM) training on 25 highly educated older adults. Resting-state functional connectivity (rs-FC) analysis was performed prior to and after each stimulation session with a focus on the frontoparietal control network (FPCN). The bifrontal montage with anode over the left dorsolateral prefrontal cortex enhanced VWM accuracy as compared to the sham stimulation. With the rs-FC within the FPCN, we observed significant stimulation × time interaction using bifrontal tDCS. We found no cognitive aftereffects of the frontoparietal tDCS compared to sham stimulation. Our study shows that a single bifrontal tDCS combined with cognitive training may enhance VWM performance and rs-FC within the relevant brain network even in highly educated older adults.

Endoscopic discectomy as an effective treatment of a herniated intervertebral disc.

OBJECTIVE: Prospective observational multicentre two-arm parallel study describing clinical outcome after endoscopic discectomy provided via transforaminal and interlaminar approach. BACKGROUND: Endoscopic lumbar discectomy (ELD) is a percutaneous minimally invasive procedure for the treatment of herniated lumbar discs. Herniations at lumbar intervertebral disc levels of L1/2, L2/3, L3/4 and L4/5 are mostly accessed by the transforaminal (TF) approach. However, due to the anatomic position of the iliac crest, the L5/S1 level might not be reachable by the transforaminal approach, while the interlaminar (IL) percutaneous approach should be a suitable alternative. METHODS: In a prospective observational multicentre clinical trial NCT0274311, we compared the clinical outcomes of two groups of patients who underwent ELD via IL (83) and TF (103) approach. The subjects were followed for 12 months via planned examinations by pain physicians. The levels of leg pain and back pain intensity were assessed by an 11-point numerical ratings scale (NRS). Patient's functional disability was assessed by the Oswestry Disability Index (ODI). RESULTS: Study subjects showed a significant decrease in ODI scores in both groups (p<0.001) The values of mean preoperative ODI in TF and IL groups were 39.1±15.7 and 43.4±16, respectively. Postoperative values in the latter groups were 14.8±14.9 and 17.5±14.3, respectively. Significantly lower pain scores for leg pain (p<0.001) and back pain (p<0.001) were also recorded at 12-month follow-ups. CONCLUSION: Because both procedures are strictly percutaneous; they are now more commonly performed by interventional pain physicians as a safe and effective alternative to open surgical spine procedures (Tab. 3, Fig. 7, Ref. 19).

Vitamin D status in apparently healthy medication-free Slovaks: Association to blood pressure, body mass index, self-reported smoking status and physical activity.

BACKGROUND: Vitamin D plays a role in protecting against chronic degenerative diseases. Slovak adults present one of the highest cardiovascular mortality rates among 27 EU countries. OBJECTIVES: We asked whether the 25(OH)D3 status in apparently healthy medication-free Slovaks deteriorates upon ageing, and in the presence of cardiometabolic risk factors. METHODS: We studied the impact of blood pressure, overweight/obesity, smoking, and physical activity on 25(OH)D3 levels determined using RIA method in 578 (5-81 years old) subjects. RESULTS: The average level of 25(OH)D3 was 36±17 ng/ml. A proportion of 15 % of participants were 25(OH)D3­deficient (≤20 ng/ml), 26 % presented insufficient (20-to-30 ng/ml), and 59 % satisfactory (> 30 ng/ml) levels. Neither mean 25(OH)D3 levels, nor the prevalence of hypovitaminosis D showed age dependence. Physically active normotensive non-smokers presented the highest (41±19 ng/ml), and their smoking counterparts with elevated BP the lowest 25(OH)D3 levels (30±12 ng/ml). CONCLUSION: In apparently healthy medication-free Slovaks the prevalence of hypovitaminosis D is high. Vitamin D status does not deteriorate in course of healthy ageing. Physical activity, normotension, and non-smoking status are associated with favorable vitamin D status while low 25(OH)D3 levels are associated with multiple cardiometabolic risk factors. Further studies in subjects at high cardiovascular risk are needed to elucidate the potential association of hypovitaminosis D with high cardiovascular mortality in Slovak adults (Tab. 1, Fig. 4, Ref. 42).

High-frequency - Spinal Cord Stimulation.

AIM: Our clinical experience with high - frequency SCS for FBSS in patients with predominant low back pain is presented. MATERIAL AND METHODS: After a trial period, 100 % (21 out of 21) of patients with FBSS with predominant low back pain reported a significant improvement in visual analog scale (VAS) pain score and underwent permanent implantation of the high - frequency SCS system. SCS trials lasted 7-14 days (median 9 days). SCS leads were mostly positioned at the T8-10 or T8-12 vertebral levels . We used both single and dual lead placement. VAS, patient satisfaction, patient performance status, opioid consumption and complication rate were assessed for the period of 12 months. RESULTS: The mean VAS score before implantation (8.7) compared to VAS 12 months after implantation (4.0) was significantly lower (CI95[3.9-5.4], p < 0.001). There was a significant improvement in performance status when comparing PS before implantation (3.0) and 12 months after implantation (1.8) (CI95[0.9-1.6], p < 0.001). The mean patient satisfaction scores (PSS) did not differ throughout the whole one year follow-up period. CONCLUSION: Our group of 21 patients with implanted high - frequency SCS systems reported significant low back pain and leg pain relief within the period of 12 months as well as significant improvement in their performance status. We had a special subgroup of 5 patients with regular change of frequencies between high frequency and conventional frequency (with paresthesia) also with significant leg and low back pain relief (Tab. 2, Fig. 1, Ref. 8). Text in PDF www.elis.sk.

Exploring the impact of intensified multiple session tDCS over the left DLPFC on brain function in MCI: a randomized control trial.

Transcranial direct current stimulation combined with cognitive training (tDCS-cog) represents a promising approach to combat cognitive decline among healthy older adults and patients with mild cognitive impairment (MCI). In this 5-day-long double-blinded randomized trial, we investigated the impact of intensified tDCS-cog protocol involving two trains of stimulation per day on working memory (WM) enhancement in 35 amnestic and multidomain amnestic MCI patients. Specifically, we focused to improve WM tasks relying on top-down attentional control and hypothesized that intensified tDCS would enhance performance of visual object matching task (VOMT) immediately after the stimulation regimen and at a 1-month follow-up. Secondarily, we explored whether the stimulation would augment online visual working memory training. Using fMRI, we aimed to elucidate the neural mechanisms underlying the intervention effects by analyzing BOLD activations during VOMT. Our main finding revealed no superior after-effects of tDCS-cog over the sham on VOMT among individuals with MCI as indicated by insignificant immediate and long-lasting after-effects. Additionally, the tDCS-cog did not enhance online training as predicted. The fMRI analysis revealed brain activity alterations in right insula that may be linked to tDCS-cog intervention. In the study we discuss the insignificant behavioral results in the context of the current evidence in tDCS parameter space and opening the discussion of possible interference between trained cognitive tasks.

CHANGES IN THE VISION OF ADULT AMBLYOPIC PATIENTS FOLLOWING CLEAR LENS EXTRACTION.

AIMS: The aim of the study was to retrospectively evaluate changes in vision after the implantation of trifocal (tIOL) or rotationally asymmetric multifocal artificial intraocular lenses (mIOL) in patients undergoing clear lens extraction. The main goal was to determine whether changes to central visual acuity occur after the implantation of an IOL at a follow-up examination after one year. Other objectives were to determine the difference between the groups with implanted diffractive and rotationally asymmetric artificial intraocular lenses, as well as to evaluate the risk of accurate correction in patients who had lived most of their lives "undercorrected". MATERIAL AND METHODS: In our study, we present a retrospective longitudinal evaluation of results in patients after the implantation of an artificial intraocular lens. In the period from 2013 to 2020, we evaluated changes in the vision of 22 patients aged 39-59 years, of whom 18 were women and 5 were men. The average preoperative refraction of myopic eyes was +5.7 ±2.13 Dsf and +1.24 ±0.86 Dcyl. In amblyopic eyes, 7 diffractive lenses and 15 rotationally asymmetric lenses were used. RESULTS: Uncorrected distance visual acuity before surgery and one year (1Y) after was 0.13 ±0.09 vs. 0.57 ±0.28 (p < 0.001); the best corrected distance visual acuity before and 1Y after was 0.53 ±0.22 vs. 0.62 ±0.29 (p = 0.024); uncorrected near visual acuity before and 1Y after was 0.06 ±0.06 vs. 0.48 ±0.32 (p < 0.001); the best corrected near visual acuity before and afér the surgical procedure was 0.45 ±0.27vs. 0.55 ±0.35 (p = 0.014). CONCLUSION: Implantation of tIOL and mIOL lenses was effective in our group of patients with amblyopia, thus improving uncorrected distance and near visual acuity and without serious adverse effects. At the same time, we evaluate that the change in refraction and the removal of anisometropia lead to a significant change in the best corrected visual acuity for distance or near vision at the one-year follow-up examination.

Gliosarcoma with alveolar rhabdomyosarcoma-like component: report of a case with a hitherto undescribed sarcomatous component.

UNLABELLED: Gliosarcoma (GS) is a relatively rare glioblastoma variant characterized by biphasic glial and mesenchymal differentiation patterns. The sarcomatous part most commonly resembles fibrosarcoma or so-called malignant fibrous histiocytoma. Rarely, GS shows heterologous lines of differentiation in the form of osteosarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, squamous or glandular malignant epithelial differentiation, or primitive neuroectodermal tumor (PNET)-like foci. When rhabdomyoblastic differentiation occurs, it is in the form of malignant spindle cells, with cross-striated strap cells or rounded rhabdomyoblasts reminiscent of the embryonal type of rhabdomyosarcoma. We are reporting a case of GS with an alveolar rhabdomyosarcoma-like component. The tumor consisted of poorly differentiated primitive small round cells growing in a solid and alveolar pattern, with minimal cytoplasm, markedly elevated mitotic activity and numerous apoptotic nuclei. Rhabdomyosarcomatous differentiation was confirmed by desmin and myogenin immunopositivity. To the best of our knowledge, this histologic pattern has not been previously reported in GS. Differential diagnostic considerations are discussed. KEYWORDS: gliosarcoma - alveolar rhabdomyosarcoma - myogenin - desmin.

USE OF A FEMTOSECOND LASER IN CATARACT SURGERY.

AIMS: Cataracts continue to be the leading cause of blindness worldwide. Phacoemulsification is the gold standard in the treatment of cataracts. The aim of the study was to compare the postoperative results of the phacoemulsification technique in comparison with femtosecond laser-assisted cataract surgery (FLACS). MATERIAL AND METHODS: Our work retrospectively evaluates the results of patients after implantation of an artificial intraocular lens for cataract from May 2017 to March 2019. The study evaluated a total of 80 implanted lenses in 47 patients operated on by two surgeons. Of the 47 patients, 28 were women. The mean age in the group at the time of surgery was 63.7 years, ranging from 34-79 years. Patients could choose FLACS (n = 45) surgery or standard phacoemulsification procedure (n = 35). RESULTS: Upon a comparison of the group regarding uncorrected distal visual acuity (UCDVA) up to 12 months after surgery, the group FAKO CATARACTS recorded 0.85 ±0.18 vs. 0.93 ±0.12 in the FEMTO CATARACTS group (p = 0.021), comparably uncorrected near visual acuity (UCNVA) was 0.77 ±0.18 vs. 0.84 ±0.17 (p = 0.034) respectively. A difference in the use of phacoemulsification energy (OZIL) was measured in patients with phacoemulsification 3.5 ±3.1 and in the use of femtosecond laser 2.2 ±3.1, (p = 0.005). In all cases, an AT LISA 839 trifocal lens (Carl Zeiss Meditec, Germany) was implanted. CONCLUSION: The femtosecond platform assists the surgeon in cataract surgery with capsulorhexis and pre-fragmentation of the lens nucleus, which can be advantageous especially for complicated cataracts. We recorded significantly higher uncorrected distance and near visual acuity in the FLACS group, and also a significantly lower value of the phacoemulsification energy used.

[Osteochondroma of the iliac crest: case report]. / Osteochondróm lopaty iliakálnej kosti.

The authors present the case of a 16-year-old boy with osteochondroma of the iliac crest which gradually resulted in gluteal muscle atrophy, developing curvature of the spine and compression of the external iliac artery. Osteochondroma excision prevented the development of circulatory disorders in the ipsilateral lower extremity, and effective physical therapy enabled the well cooperating patient to restore fully his gluteal muscle strength and normal gait pattern.

[Interbody spacers in the treatment of cervical spine disorders]. / Náhrady medzistavcových platniciek v liecbe degeneratívnych ochorení krcnej chrbtice.

Degenerative conditions of the spine represent a group of most common lifestyle associated diseases with significant medical and important social impact. Clinical symptoms and syndromes of surgically considerable degenerative diseases of the spine mostly result from nerve root or spinal cord compression caused by a herniated intervertebral disc or a dorsal osteophyte. Therefore, the main goal of the surgical treatment is decompression of the neural structures by complete removal of the intervertebral disc and the osteophytes followed by insertion of an artificial disc spacer into the remaining space. The most frequently used procedure for treating such findings is called anterior cervical discectomy. Since its first introduction in 1950, several modifications of the original technique have been introduced. Their common feature is that removal of the degenerated intervertebral disc or the osteophytes requires stabilization of the adjacent segments by fusion. Thus, implantation of an interbody spacer results not only in intervertebral space reconstruction, but by immobilizing the adjacent vertebral bodies also in forming a firm bony bridging between them--and ultimately a solid bony block. Our paper provides a review of cervical interbody spacers in the order of their evolution from auto- and allografts, through compact materials, cages and dynamic artificial disks. Furthermore, different types of cage filling materials used for fusion augmentation are also discussed.

[Surgical management of the failed back surgery syndrome (FBSS) using posterior lumbar interbody fusion (PLIF) with posterior transpedicular stabilization]. / Chirurgické riesenie failed back surgery syndrómu FBSS pomocou zadnej lumbálnej medzitelovej fúzie PLIF so zadnou transpedikulárnou stabilizáciou.

INTRODUCTION: One of possibility of treatment FBSS is posterior lumbar interbody fusion, PLIF with posterior transpedicular stabilization. MATERIAL AND METHODS: Between January 2005 and December 2007, the prospective study of treatment failed back surgery syndrome patients with posterior lumbal interbody fusion and posterior transpedicular stabilization was performed at the Department of Neurosurgery University Hospital FNLP in Kosice. Physical examinations were performed before surgery, after surgery 30 days, and at 4 follow-up visits (3 months, 6 months, 12 months and 24 months). At each interval, patients outcomes measures, including visual analog scale pain rating VAS and Oswestry Disability Index ODI. RESULTS: At the Department of Neurosurgery, 58 failed back surgery syndrome patients were operated on between 1.1.205 and 31.12. 2007. Long term follow up was investigated in 47 patients, 11 patients were lost to follow-up. Postoperative complications were controlled 30 days after surgery. They were presented in 9 patients (19.14%). No patient died after surgery. The working ability was found in 23 patients 49%. Before surgery all patiens used analgesic, after surgery there were present decrese in using analgesic. Improvement quality of life and decrease pain measured with ODI and VAS were investigated. ODI before surgery was 71.7 and 24 months after surgery ODI was 37.7. VAS before surgery was 7.95 and 24 months after surgery VAS was 2.82. There were found statistically significant influence on decrease pain mesuares ODI and VAS after surgery p < 0.0001. CONCLUSION: Our study results show that PLIF with posterior transpedicular stabilization can be safely perfomed and that can allow decrease pain and improve quality of life in FBSS patients.

Functional results in patients with sarcoma around the knee joint.

Authors evaluated functional outcomes after three different surgical procedures for sarcoma around the knee joint. Sixteen patients with sarcoma were given four to six preoperative courses of chemotherapy. Patients were separated into three groups according to the pattern of tumour excision. The first group underwent the resection of proximal fibula and tibialis anterior muscle resection, the second group underwent resection of distal femur or proximal tibia with total knee replacement, and the third group underwent radical amputation. The mean functional evaluations were 100, 95 and 80%. All marginal resections of proximal fibula resulted in excellent function. No local evidence of tumour recurrence was seen at mean follow-up of 24 months (Tab. 1, Fig. 2, Ref. 7).

[First experience with correction of limb-length inequality and angular and rotational deformities of the tibia using the Taylor spatial frame]. / Korekcia uhlových, dlzkových a rotacných deformít predkolenia Taylorovým priestorovým rámom--prvé skúsenosti.

The authors analyse the first results of correction surgery for limb-length inequality and rotational and angular deformities of the tibia using the Taylor spatial frame in combination with the Ilizarov external fixator in three patients. The shortening of the tibia, 65 mm on the average (55, 60 and 80 mm, respectively), was due to tibial hemimilia in two patients and traumatic epiphyseolysis of the distal tibia in one patient. Distraction at a rate of 1 mm/day was controlled three-times a day on two contralateral struts. It started on the seventh day after osteotomy in all three patients. On the second post-operative day, rehabilitation started with standing up and walking with crutches. The additional fixation of the heel and foot was removed at 3 months after distraction was terminated so that ankle exercise would be possible. No serious complications were recorded. The average distraction index was 0.91 and the average tibial lengthening was 65 mm. Callus consolidation was achieved at 131 days after the end of distraction phase. Approximately at 10 months post-operatively, the patients reported full weight-bearing of the extremity.

A critical gap between recommended and achieved LDL-cholesterol levels. Results of statin therapy in Slovakia.

BACKGROUND: The achievement of low density lipoprotein cholesterol (LDL-C) target levels, as recommended by the evidence-based international guidelines, represents the crucial prerequisite for maximal cardiovascular risk reduction in patients with dyslipidemia. OBJECTIVES: The efficacy of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) monotherapy administered in ambulatory practice was evaluated in cooperation with 387 ambulatory specialists in Slovakia. PATIENTS AND METHODS: Data of 5640 adult patients (21-88 years, 42.8% males) with low (7.4%), high (16.8%), and very high cardiovascular risks (75.7%), treated at least for 12 weeks with a stable statin dose were evaluated regarding the achievement of target LDL-C levels (< 4.2 mmol/L in low risk patients, < 3.4 mmol/L in high risk patients and < 2.6 mmol/L in very high risk patients). RESULTS: The target levels were achieved in 74% of low risk patients (mean level of LDL-C 3.55 mmol/L), in 37.9% of high risk patients (3.7 mmol/L), and in 12.4% of very high risk patients (3.64 mmol/L). The proportion of received statins and their average daily doses were as follows: 64.3% simvastatin (22.5 mg); 21.3% atorvastatin (15.6 mg); 12.2% fluvastatin (69.7 mg); 1.5% pravastatin (19.4 mg), and 0.7% lovastatin (25.4 mg). CONCLUSION: Statin therapy does not correspond with the current guidelines in common clinical practice. In patients with treated hypercholesterolemia the use of low doses of statins without titration seems to be the main reason of poor achieving of LDL-C target levels representing the critical values for reducing the atherosclerosis and its life-threatening complications (Tab. 3, Fig. 1, Ref 19). Full Text (Free, PDF) www.bmj.sk.

"Different" approach in the operative treatment of congenital clubfoot and its results.

OBJECTIVES: This study compared long-term results of the treatment of idiopathic clubfoot at two different University orthopaedic departments. BACKGROUND: The treatment of clubfoot is still controversial due to different severity and different treatment philosophies. METHODS: Authors retrospectively analyzed a group of 273 feet (145 patients) operated on at the Unit of Pediatric orthopaedics, Children University Hospital, Bratislava (group A) and the cohort of 60 feet (33 patients) operated on at the Ist University Department of Orthopaedics, Bratislava (group B), between 1993 and 2002 with follow up period from 2 to 11 years (average 72 months). In the group A, McKay procedure was indicated in 3 feet, Carroll operation in 35 feet and 160 feet were operated by Brockmanns posteromedial release and its modifications (cuboid and metatarsal osteotomies). In the group B, McKay procedure was done in 8 feet and 50 feet were operated on by Turco/ Zacepin procedure. RESULTS: Recurrences in both groups due to the insufficient first step operative reduction and mistakes in after treatment were 12%. Satisfactory results (excellent and good) were achieved in 88% of cases in both groups. CONCLUSION: This study shows, that the results of operative treatment of congenital clubfoot from two different departments (using different operative techniques but "a la carte philosophy") were comparable in most of the cases (Tab. 4, Fig. 3, Ref: 9).

Diazepam enhances hypericin-induced photocytotoxicity and apoptosis in human glioblastoma cells.

Glioblastoma multiforme (GBM) is neoplasm which is resistant to all currently used treatment modalities including surgery, radiation therapy and chemotherapy. Photodynamic therapy (PDT) has been suggested as a novel therapeutical approach to the treatment of malignant gliomas. Here, we attempted to enhance hypericin-induced photocytotoxicity and apoptosis by diazepam, a non-selective ligand of peripheral benzodiazepine receptors (PBR) which seem to play an important role in apoptosis regulation. For the study, we used U-87 MG and U373 MG glioma cell lines and primary cultures of GBM cells prepared from peroperatively obtained tumor specimens. The patients included 7 histologically confirmed GBMs. Colorimetric MTT assay was employed to study the photocytotoxic effects of hypericin and diazepam. Flow cytometry was used to detect apoptosis and assess the proapoptotic effects of diazepam. We found that hypericin upon photoactivation exerts strong cytotoxic effects against U-87 MG and U373 MG cells as well as primary GBM cell cultures. No cytotoxic effect of hypericin was observed under dark conditions. Diazepam inhibited cell growth in U-87 MG cells and primary cultures whereas proliferation of U373 MG cells remained unaffected. When hypericin was combined with diazepam, photocytotoxicity was increased in U-87 MG cells and primary cultures unlike U373 MG cells. Flow cytometric analysis revealed photoactivated hypericin-induced apoptosis in both cell lines. Apoptosis was significantly enhanced by diazepam in U-87 MG cells. However, no such effect was observed in U373 MG cells. In the present study, we showed that photocytotoxic effect of hypericin in glioma cells can be potentiated by diazepam. This effect is underlied by the ability of diazepam to facilitate hypericin-induced apoptosis. This work provides support to performe clinical studies involving diazepam in the antiglioma treatment regimens as an apoptosis-modulating agent.

Nitric oxide modulation of metabolic and haemodynamic balance.

Nitric oxide (NO) belongs to signal molecules and modulates notably rapid and dynamic processes. Interests are focused on the decreased NO synthesis by endothelial and mitochondrial nitric oxide synthases with the metabolic (i.e. insulin resistance, diabetes, energetical dysbalance) and vascular (i.e. hypertension, atheroslerosis) consequences. A significant source of NO are NO-donors (i.e. organic nitrates). A number of antihypertensive drugs stimulates NO production or inhibits the production of its antagonists (angiotensin II, catecholamines), other drugs (i.e. glucocorticoids) inhibit NO production. These interferences are targets of an intensive research with the aim of NO dysbalance prevention, hypertension and metabolic dysbalances correction. While the clinical research concentrates on NO and insulin resistance, the molecular biological research concentrates on "mitochondrial medicine" with the ambition to formulate a new theory of aging, carcinoma, and other fundamental biological processes (Fig. 1, Ref. 47).

Effective long-term inhibition of thromboxane production but not of serotonin release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid dosage.

Efficacy of aspirin (Acetylsalicylic acid, ASA) antiaggregatory prevention was demonstrated in a series of clinical trials. The recommended ASA doses decreased gradually and doses 50-30 mg ASA/d are intensively studied at the present time. A group of 42 patients with coronary heart disease was evaluated: (1) Basal TXB2 production during spontaneous blood clotting was 360 +/- 37.6 ng/ml; (2) Two initial doses were tested: while 200 mg ASA inhibited, during spontaneous blood clotting, median TXB2 production by 99.9% (serum TXB2 concentration 1.35 ng/ml), 30 mg ASA median inhibition was just 42.0% (serum TXB2 151 ng/ml); (3) 30 mg ASA/d maintenance dose was evaluated for 3 months. The median TXB2 production inhibition was 98.5% (serum TXB2 3.75 ng/ml, first month) and 94.0% (serum TXB2 14.2 ng/ml, third month); (4) Four patients did not respond sufficiently, because of noncompliance verified by the determination of salicyluric acid urinary excretion, the lower limit of excretion being <3 micromol/2 h; (5) Both initial and maintenance ASA dose decreased metabolic TXA2 endproducts in urine; (6) 5HT platelet release did not decrease; (7) Potential changes of 5HT metabolic elimination were excluded by the simultaneous determination of 5-hydroxyindoleacetic acid (5HIAA). In conclusion, 200 mg initial dose and 30 mg ASA/d maintenance dose are suggested to be maximally inhibitory for TXB2 production without influence on 5HT release.

Serum hippurate and its excretion in conservatively treated and dialysed patients with chronic renal failure.

54 healthy volunteers or patients with normal kidney and liver function, 17 patients with decreased kidney function and 12 dialysed patients were evaluated for their serum hippurate accumulation and kidney excretion. It was found that there was an inverse relationship between serum hippurate and the clearance of endogenous creatinine (CCr) and a free relationship between fractional excretion of hippurate and CCr. The excretory capacity in residual nephrons was increased. This was caused by the greater glomerular filtration load which increased up to 25 times and tubular secretion which increased 7 times in dialysed patients. The relative contribution of glomerular filtration to hippurate excretion rose from about 20% in controls to almost 50% in dialysed patients. True kidney adaptation was localized in the organic anion transport system of proximal tubules.