MM165 - A Small Hybrid Molecule Modulates the Kynurenine Pathway and Attenuates Lipopolysaccharide-Induced Memory Deficits and Inflammation.

Cognitive dysfunctions are now recognized as core symptoms of various psychiatric disorders e.g., major depressive disorder. Sustained immune activation may leads to cognitive dysfunctions. Proinflammatory cytokines shunt the metabolism of tryptophan towards kynurenine and quinolinic acid may accumulate at toxic concentrations. This acid triggers an increase in neuronal nitric oxide synthase function and promotes oxidative stress. The searching for small molecules that can regulate tryptophan metabolites produced in the kynurenic pathway has become an important goal in developing treatments for various central nervous system diseases with an inflammatory component. Previously we have identified a small hybrid molecule - MM165 which significantly reduces depressive-like symptoms caused by inflammation induced by lipopolysaccharide administration. In the present study, we investigated whether this compound would mitigate cognitive deficits induced by lipopolysaccharide administration and whether treatment with it would affect the plasma or brain levels of quinolinic acid and kynurenic acid. Neuroinflammation was induced in rats by administering lipopolysaccharide at a dose of 0.5 mg/kg body weight for 10 days. We conducted two tests: novel object recognition and object location, to assess the effect on memory impairment in animals previously treated with lipopolysaccharide. In plasma collected from rats, the concentrations of C-reactive protein and tumor necrosis factor alfa were determined. The concentrations of kynurenic acid and quinolinic acid were determined in plasma and homogenates obtained from the cerebral cortex of rats. Interleukin 6 in the cerebral cortex of rats was determined. Additionally, the body and spleen mass and spontaneous activity were measured in rats. Our study shows that MM165 may mitigate cognitive deficits induced by inflammation after administration of lipopolysaccharide and alter the concentrations of tryptophan metabolites in the brain. Compounds exhibiting a mechanism of action analogous to that of MM165 may serve as foundational structures for the development of a new class of antidepressants.

Manifestations of Liver Impairment and the Effects of MH-76, a Non-Quinazoline α1-Adrenoceptor Antagonist, and Prazosin on Liver Tissue in Fructose-Induced Metabolic Syndrome.

Excessive fructose consumption may lead to metabolic syndrome, metabolic dysfunction-associated fatty liver disease (MAFLD) and hypertension. α1-adrenoceptors antagonists are antihypertensive agents that exert mild beneficial effects on the metabolic profile in hypertensive patients. However, they are no longer used as a first-line therapy for hypertension based on Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) outcomes. Later studies have shown that quinazoline-based α1-adrenolytics (prazosin, doxazosin) induce apoptosis; however, this effect was independent of α1-adrenoceptor blockade and was associated with the presence of quinazoline moiety. Recent studies showed that α1-adrenoceptors antagonists may reduce mortality in COVID-19 patients due to anti-inflammatory properties. MH-76 (1-[3-(2,6-dimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride)) is a non-quinazoline α1-adrenoceptor antagonist which, in fructose-fed rats, exerted anti-inflammatory, antihypertensive properties and reduced insulin resistance and visceral adiposity. In this study, we aimed to evaluate the effect of fructose consumption and treatment with α1-adrenoceptor antagonists of different classes (MH-76 and prazosin) on liver tissue of fructose-fed rats. Livers were collected from four groups (Control, Fructose, Fructose + MH-76 and Fructose + Prazosin) and subjected to biochemical and histopathological studies. Both α1-adrenolytics reduced macrovesicular steatosis and triglycerides content of liver tissue and improved its antioxidant capacity. Treatment with MH-76, contrary to prazosin, reduced leucocytes infiltration as well as decreased elevated IL-6 and leptin concentrations. Moreover, the MH-76 hepatotoxicity in hepatoma HepG2 cells was less than that of prazosin. The use of α1-adrenolytics with anti-inflammatory properties may be an interesting option for treatment of hypertension with metabolic complications.

Antiplatelet Effects of Selected Xanthine-Based Adenosine A2A and A2B Receptor Antagonists Determined in Rat Blood.

The platelet aggregation inhibitory activity of selected xanthine-based adenosine A2A and A2B receptor antagonists was investigated, and attempts were made to explain the observed effects. The selective A2B receptor antagonist PSB-603 and the A2A receptor antagonist TB-42 inhibited platelet aggregation induced by collagen or ADP. In addition to adenosine receptor blockade, the compounds were found to act as moderately potent non-selective inhibitors of phosphodiesterases (PDEs). TB-42 showed the highest inhibitory activity against PDE3A along with moderate activity against PDE2A and PDE5A. The antiplatelet activity of PSB-603 and TB-42 may be due to inhibition of PDEs, which induces an increase in cAMP and/or cGMP concentrations in platelets. The xanthine-based adenosine receptor antagonists were found to be non-cytotoxic for platelets. Some of the compounds showed anti-oxidative properties reducing lipid peroxidation. These results may provide a basis for the future development of multi-target xanthine derivatives for the treatment of inflammation and atherosclerosis and the prevention of heart infarction and stroke.

Preliminary Evidence of the Potent and Selective Adenosine A2B Receptor Antagonist PSB-603 in Reducing Obesity and Some of Its Associated Metabolic Disorders in Mice.

The adenosine A2A and A2B receptors are promising therapeutic targets in the treatment of obesity and diabetes since the agonists and antagonists of these receptors have the potential to positively affect metabolic disorders. The present study investigated the link between body weight reduction, glucose homeostasis, and anti-inflammatory activity induced by a highly potent and specific adenosine A2B receptor antagonist, compound PSB-603. Mice were fed a high-fat diet for 14 weeks, and after 12 weeks, they were treated for 14 days intraperitoneally with the test compound. The A1/A2A/A2B receptor antagonist theophylline was used as a reference. Following two weeks of treatment, different biochemical parameters were determined, including total cholesterol, triglycerides, glucose, TNF-α, and IL-6 blood levels, as well as glucose and insulin tolerance. To avoid false positive results, mouse locomotor and spontaneous activities were assessed. Both theophylline and PSB-603 significantly reduced body weight in obese mice. Both compounds had no effects on glucose levels in the obese state; however, PSB-603, contrary to theophylline, significantly reduced triglycerides and total cholesterol blood levels. Thus, our observations showed that selective A2B adenosine receptor blockade has a more favourable effect on the lipid profile than nonselective inhibition.

Hydroalcoholic Leaf Extract of Isatis tinctoria L. via Antioxidative and Anti-Inflammatory Effects Reduces Stress-Induced Behavioral and Cellular Disorders in Mice.

Stress that can occur at different levels of a person's life can cause and exacerbate various diseases. Oxidative stress and inflammation underlie this process at the cellular level. There is an urgent need to identify new and more effective therapeutic targets for the treatment of stress-induced behavioral disorders and specific drugs that affect these targets. Isatis tinctoria L. is a herbaceous species in the Brassicaceae family. Due to its potential antioxidant, nitric oxide- (NO-) inhibiting, anti-inflammatory, and neuroprotective properties, I. tinctoria could be used to treat depression, anxiety, and stress resistance. Hence, the present study is aimed at delineating whether administration of I. tinctoria leaf extract may improve stress-induced disorders in mice. A set of four behavioral tests was selected that together are suitable for phenotyping acute restraint stress-associated behaviors in mice, namely locomotor activity, social integration, dark/light box, and splash tests. The plasma and brains were collected. A brain-derived neurotrophic factor, tumor necrosis factor-alpha, C-reactive protein, corticosterone, NO, reactive oxygen species levels, superoxide dismutase and catalase activity, and ferric-reducing antioxidant power were measured. In mice stressed by immobilization, decreased locomotor activity, anxiety-like behavior, and contact with other individuals were observed, as well as increased oxidative stress and increased levels of nitric oxide in the brain and plasma C-reactive protein. A single administration of I. tinctoria leaf extract was able to reverse the behavioral response to restraint by a mechanism partially dependent on the modulation of oxidative stress, neuroinflammation, and NO reduction. In conclusion, Isatis tinctoria hydroalcoholic leaf extract can reduce stress-induced behavioral disturbances by regulating neurooxidative, neuronitrosative, and neuroimmune pathways. Therefore, it could be recommended for further research on clinical efficacy in depression and anxiety disorder treatment.

PSB 603 - a known selective adenosine A2B receptor antagonist - has anti-inflammatory activity in mice.

A2B adenosine receptors are present in a wide spectrum of tissues, especially on cells of the immune system. Since these particular receptors have the lowest, of all adenosine receptor subtypes, affinity for adenosine they are believed to play a special role in immunological processes associated with elevated adenosine levels such as inflammation. The aim of this preliminary study was to determine the potential anti-inflammatory properties of compound PSB-603, a potent and selective adenosine A2B receptor antagonist, in two different experimental models of local and systemic inflammation. In a model of inflammation induced by local carrageenan administration paw edema was measured using a pletysmometer. Additionally, levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and reactive oxygen species (ROS) were determined in the inflamed paw. Using the mouse model of peripheral inflammation induced by intraperitoneal (ip) administration of zymosan A, the influence of the A2B antagonist on the infiltration of neutrophils into the peritoneum and its effect on the plasma levels of CRP, TNF-α, and IL-6 were investigated. The results showed that PSB-603 administered at a dose of 5 mg/kg b.w. ip significantly reduced inflammation in both tested models. Particularly, it significantly decreased levels of the inflammatory cytokines IL-6, TNF-α and of ROS in the inflamed paw and reduced inflammation of the peritoneum by significantly decreasing the infiltration of leukocytes. Additionally, in the latter model, no statistically significant difference was observed in the CRP level between the control group without inflammation and the group which has been treated with the PSB-603 compound. Thus, the results may indicate the anti-inflammatory activity of adenosine A2B receptor antagonists in two different models of inflammation.

KD-64-A new selective A2A adenosine receptor antagonist has anti-inflammatory activity but contrary to the non-selective antagonist-Caffeine does not reduce diet-induced obesity in mice.

The A2 adenosine receptors play an important role, among others, in the regulation of inflammatory process and glucose homeostasis in diabetes and obesity. Thus, the presented project evaluated of influence of the selective antagonist of A2A adenosine receptor-KD-64 as compared to the known non-selective antagonist-caffeine on these two particular processes. Two different inflammation models were induced namely local and systemic inflammation. Obesity was induced in mice by high-fat diet and the tested compounds (KD-64 and caffeine) were administrated for 21 days. KD-64 showed anti-inflammatory effect in both tested inflammation models and administered at the same dose as ketoprofen exerted stronger effect than this reference compound. Elevated levels of IL-6 and TNF-α observed in obese control mice were significantly lowered by the administration of KD-64 and were similar to the values observed in control non-obese mice. Interestingly, caffeine increased the levels of these parameters. In contrast to caffeine which had no influence on AlaT activity, KD-64 administration significantly lowered AlaT activity in the obese mice. Although, contrary to caffeine, KD-64 did not reduce diet-induced obesity in mice, it improved glucose tolerance. Thus, the activity of the selective adenosine A2A receptor antagonist was quite different from that of the non-selective.

KSK19 - Novel histamine H3 receptor ligand reduces body weight in diet induced obese mice.

AIMS: Histamine H3 receptors ligands act anorectic by blocking the H3 autoreceptors in the CNS, that results in increased synthesis and disinhibition of histamine release. Histamine further influencing H1 receptors participates in the leptin-dependent inhibition of food intake. It also affects the peripheral metabolism by increasing white adipose tissue lipolysis. Thus, ligands such as KSK19 with significant antagonistic properties at the H3 receptor might serve as an useful treatment for obesity. MATERIALS AND METHODS: To induce obesity, female CD-1 mice were fed a high-fat diet for 14 weeks. The test compound at the doses of 10 or 15 mg/kg, i.p. was administrated for 21 days. Glucose and insulin tolerance tests was performed at the beginning of week 15. At the end of study, amount of intraperitoneal fat pads, AlAT, IL-6 and TNF-α plasma levels were determined. RESULTS: Animals fed with high-fat diet and treated with test compound at the dose of 15 mg/kg showed significantly less weight gain, than mice from the control group. The use of KSK19 for 21 days in obese mice also significantly improved glucose tolerance and insulin resistance. In the tested doses KSK19 did not affect locomotor activity neither in lean nor in obese mice after single i.p. administration, but spontaneous activity increased during three hour after twentieth administrations. CONCLUSION: KSK19 is a strong, selective histamine H3 receptor antagonist with a favorable influence on body weight after multiple administration at the dose of 15 mg/kg. Moreover it significantly improves glucose tolerance.

Synthesis and Pharmacological Evaluation of Novel Silodosin-Based Arylsulfonamide Derivatives as α1A/α1D-Adrenergic Receptor Antagonist with Potential Uroselective Profile.

Benign prostatic hyperplasia (BPH) is the most common male clinical problem impacting the quality of life of older men. Clinical studies have indicated that the inhibition of α1A-/α1D adrenoceptors might offer effective therapy in lower urinary tract symptoms. Herein, a limited series of arylsulfonamide derivatives of (aryloxy)ethyl alicyclic amines was designed, synthesized, and biologically evaluated as potent α1-adrenoceptor antagonists with uroselective profile. Among them, compound 9 (3-chloro-2-fluoro-N-([1-(2-(2-(2,2,2-trifluoroethoxy)phenoxy]ethyl)piperidin-4-yl)methyl)benzenesulfonamide) behaved as an α1A-/α1D-adrenoceptor antagonist (Ki(α1) = 50 nM, EC50(α1A) = 0.8 nM, EC50(α1D) = 1.1 nM), displayed selectivity over α2-adrenoceptors (Ki(α2) = 858 nM), and a 5-fold functional preference over the α1B subtype. Compound 9 showed adequate metabolic stability in rat-liver microsome assay similar to the reference drug tamsulosin (Clint = 67 and 41 µL/min/mg, respectively). Compound 9 did not decrease systolic and diastolic blood pressure in normotensive anesthetized rats in the dose of 2 mg/kg, i.v. These data support development of uroselective agents in the group of arylsulfonamides of alicyclic amines with potential efficacy in the treatment of lower urinary tract symptoms associated to benign prostatic hyperplasia.

Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.

Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D2 receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62). The polypharmacology profile of 62, characterized by partial 5-HT1AR agonism, 5-HT2A/5-HT7/D2/D3R antagonism, and blockade of SERT, reduced the "positive"-like, and "negative"-like symptoms of psychoses. Compound 62 produced no catalepsy, demonstrated a low hyperprolactinemia liability and displayed pro-cognitive effects in the novel object recognition task and attentional set-shifting test. While association of in vitro features with the promising in vivo profile of 62 is still not fully established, its clinical efficacy should be verified in further stages of development.

The effect of NaCl on the level of reduced sulfur compounds in rat liver. Implications for blood pressure increase.

BACKGROUND: It is commonly known that excessive salt intake is a risk factor of hypertension. Currently, there is an increasing interest in reduced reactive sulfur species (RSS), mainly H2S and sulfane sulfur (SS) as new gasotransmitters showing vasorelaxant properties. The aim of the present study was to determine the effect of repeated administration of low sodium chloride dose included in physiological saline on blood pressure, on the level of RSS and activity of enzymes involved in their biosynthesis in the rat. METHODS: Two separate experiments were carried out on male Wistar rats: one with intravenous injections of saline and the second one with intraperitoneal saline injections. Blood pressure was measured during the experiment. The level of RSS and other biochemical assays were conducted in the rat liver, because of an intense cysteine metabolism to RSS in this organ. RESULTS: Intravenous administration of saline induced a significant increase in systolic blood pressure while intraperitoneal injections showed only a tendency towards increasing blood pressure. The RSS (H2S and SS) level as well as the activity of the main enzyme responsible for their production in the liver of animals after iv saline injections were decreased. Animals injected with physiological saline by ip route did not reveal any statistically significant differences in SS, H2S, and activities of sulfurtransferases, although a tendency to decrease in the RSS was observed. CONCLUSIONS: The repeated iv saline injection induced a slight hypertension accompanied by disturbances in anaerobic cysteine metabolism in the rat liver.

Antiarrhythmic activity in occlusion-reperfusion model of 1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino} propan-2-ol and its enantiomers.

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide, especially in developed countries. The most serious problem after myocardial infarction is reperfusion injury that manifests as functional impairment, arrhythmia, and accelerated progression of cell death in certain critically injured myocytes. Subsequently the infarcted myocardium develops features of necrosis and reactive inflammation. To reduce lethal reperfusion injury in patient with AMI antioxidants, anti-inflammatory agents, adenosine, opioids, metabolic modulators (glucose, insulin, and potassium, nicorandil and agents which reduce intracellular Ca(2+) overload and inhibit Na(+)-H(+) exchange) are used. In this study a novel compound (compound 9) 1-(1 h-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy) ethyl]amino}propan-2-ol and its enantiomers are examined in arrhythmia associated with coronary artery occlusion and reperfusion in a rat model. Antioxidant properties are also determined for test compounds using the malondialdehyde (MDA) lipid peroxidation and ferric reducing antioxidant power (FRAP) tests. In summary, the tested compounds, especially the S enantiomer has a strong antiarrhythmic activity in a model of occlusion and reperfusion of the left coronary artery which is probably related to their adrenolytic action. In contrast to carvedilol, none of the test compound reduced the lipid peroxidation but increased ferric reducing antioxidant power. In the antioxidant effect, there was no difference between the optical forms of compound 9.

Synthesis and Analgesic Activity of Annelated Xanthine Derivatives in Experimental Models in Rodents.

A series of annelated derivatives of xanthine were synthesized and assayed as potential analgesic agents. All synthesized xanthine derivatives were tested in the writhing test and hot-plate test. The pharmacological assays demonstrated that all the compounds prepared, without exception, displayed a significant activity in the mouse writhing assay. The analgesic action of the most active compounds, expressed as ED50 was found to be 1.4-4.3 times more potent than that of acetylsalicylic acid used as the reference compound. However, only some of the compounds demonstrated analgesic activity in the hot-plate test. The analgesic effect of some compounds is probably related to their agonistic, antagonistic, or partial agonistic activity at the adenosine receptors.

Tissue distribution of gold nanoparticles after single intravenous administration in mice.

BACKGROUND: Nanoparticles (a part of matter which size is less than 100 nm) have numerous potential applications in biomedicine, due to their unique surface, electronic and optical properties. The goal of the present study was to examine the distribution of gold nanoparticles (GNPs) in mice after single intravenous administration. METHODS: Spherical GNPs were synthesized by chemical reduction of tetrachloroauric acid with ascorbic acid as a reductant. GNPs were stabilized using polyvinyl alcohol (PVA, m.w. = 67000Da) a substance approved for use in the pharmaceutical industry. The size of colloidal gold particles (diameter equals 25 ± 8 nm) was determined using HR SEM and DLS techniques; ζ potential of GNPs was determined using Malvern Zetasizer Nano ZS and it equals -5.2 ± 5.4 mV. An aqueous dispersion of GNPs was administered to mice in a dose of about 10 cm(3)/kg and 24 h later the amount of gold in different organs was determined using the inductively coupled plasma mass spectrometer (ICP MS). Initial concentration of GNPs equals 29.55 mg/l. RESULTS: GNPs after single intravenous administration preferentially accumulated in the liver (12.7% of the applied dose), while the other organs accumulated around 0.1% or less. CONCLUSION: Colloidal GNPs of the used size (about 25 ± 8 nm) provide new potential route for direct delivery system to the liver, which may be important e.g., in liver cancer diagnosis.

Antiarrhythmic properties of phenylpiperazine derivatives of phenytoin with α1-adrenoceptor affinities.

An association between α(1)-adrenoceptor affinities, hERG K(+)-antagonistic properties and antiarrhythmic activities for a series of phenylpiperazine derivatives of hydantoin (2a-21a) was investigated. New compounds were synthesized and tested for their affinity for α(1)-adrenoceptors in radioligand binding assay using [(3)H]-prazosin as a selective radioligand. Antiarrhythmic activities in adrenaline- and barium chloride-induced arrhythmia models, an influence of the phenylpiperazine derivatives on the ECG-components and blood pressure were tested in vivo in normotensive rats. The hERG K(+)-antagonistic properties of the most potent antiarrhythmic agents were investigated in silico by the use of program QikProp. The highest α(1)-adrenoceptor affinity (K(i)=4.7 nM) and the strongest antiarrhythmic activity in adrenaline induced arrhythmia (ED(50)=0.1 mg/kg) was found for 1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione hydrochloride (19a). The results indicated a significant correlation between α(1)-AR affinities (pK(i)) and antiarrhythmic activity (ED(50)) in adrenaline model (R(2)=0.92, p <0.005). Influence of the examined phenylpiperazine hydantoin derivatives on hERG K(+) channel, predicted by means of in silico methods, suggested their hERG K(+)-blocking properties.

The effect of nitroglycerin tolerance on oxidative stress and anaerobic sulfur metabolism in rat tissues.

The present results indicated that tolerance to nitroglycerin (glycerin trinitrate, GTN) increased the hepatic and renal level of reactive oxygen species, malondialdehyde, and glutathione peroxidase (PO(x)) and decreased superoxide dismutase activity, whereas non-protein thiols remained unchanged in both organs. In the liver (but not in the kidney) glutathione S-transferase (GST), catalase and rhodanese activities decreased and the sulfane sulfur level also dropped. Unlike in the liver, gamma-glutamyl transpeptidase (gammaGT) activity in the kidney declined. On the other hand, hepatic S-nitrosothiols (SNT) rose while renal SNT declined. As no concomitant changes in the nitric oxide (NO) level were observed in either organ, the results suggested that under nitroglycerin tolerance NO was stored in the liver in the form of SNT. In conclusion, the results obtained in the liver and kidney confirm the involvement of oxidative stress in the pathomechanism of GTN tolerance, and reveal the diverse effects of this phenomenon on the gammaGT and GST activity and SNT level in both organs. We observed for the first time that GTN tolerance could be accompanied by the disruption of hepatic anaerobic cysteine metabolism, associated with sulfane sulfur and rhodanese activity.

[Changes of grip and pinch strength after carpal tunnel release]. / Ocena ewolucji sily chwytów po dekompresji kanalu nadgarstka.

OBJECTIVES: Evaluation of changes of the total grip strength, two-point pinch, three-point pinch, key-pinch and a subjective improvement of the dexterity of the hand measured by functional part of Levine questionnaire within first year after carpal tunnel release. PATIENTS AND METHODS: Thirty-nine patients with carpal tunnel syndrome (CTS) were evaluated for changes of aforementioned grips, pinches and completed the Levine questionnaire. All measurements were performed with set of digital dynamometers. Patients were assessed before the operation and at 3, 6 and finally at 12 months after surgery. In all cases carpal tunnel was released by double incision open technique. RESULTS: All grips and pinches improved significantly within first year after surgery with respect to preoperative values. Mean total grip strength increased at 3 months to 109%, at 6 months to 123% and at 12 months to 138%. Statistically significant difference was noted at 6 and 12 months. Mean value of two-point pinch was at 3 months of 117% preoperative value, at 3 months of 131% and at 12 months of 145%. Statistically significant difference was noted at 12 months. Mean value of three-point pinch was at 3 months of 114% preoperative value, at 6 months of 130% and at 12 months of 144%. Statistically significant difference was noted at 6 and 12 months. Mean value of key-pinch strength was at 3 months of 105% preoperative value, at 6 months of 117% and at 12 months of 145%. Statistically significant difference was noted at 6 and 12 months. Subjective evaluation of dexterity of the hand by functional part of Levine questionnaire revealed statistically significant improvement in all four post-operative examinations. CONCLUSION: Power of the hand improved gradually within whole first year after carpal tunnel release, however statistically significant difference was noted as late as at 6 and 12 months after surgery. In subjective opinion of patients the dexterity of the hand improves gradually during whole 12 months follow-up.

[Changes of the distribution of sensory disturbances and paresthesiae after carpal tunnel release]. / Ocena ewolucji zaburzen czucia i dystrybucji parestezji po dekompresji kanalu nadgarstka.

OBJECTIVES: Evaluation of changes of sensory disturbances, distribution of paresthesiae, and withdrawal of symptoms within 12 months after carpal tunnel release. PATIENTS AND METHODS: Thirty-nine patients with carpal tunnel syndrome (CTS) were evaluated for distribution of sensory disturbances. Two-point discrimination and filament testing were measured. The results were semi-quantitatively expressed as a sensory index. Distribution of paresthesiae were recorded on the whole hand, wrist and forearm. All patients completed the Levine questionnaire. Patients were assessed before the operation and at 3, 6 and 12 months after surgery. In all cases carpal tunnel was released by double incision open technique. RESULTS: Sensory index for two-point discrimination fell from initial value of 1.7 to 1.4 at 3 months, and to 1.2 at 6 months and 1 year. Index for filament testing decreased from initial 2.5 to 1.8 at 3 months, 1.5 at 6 months, and 1.7 at 1 year. Subjective patients' satisfaction measured by symptomatic part of the Levine questionnaire improved significantly within first 6 months after surgery. Paresthesiae were initially experienced on middle fingertip in 90% of patients, on index fingertip in 80% and on thumb/annular fingertips in 70%. More than 50% patients complained of these symptoms to be present on little finger and 20% on the dorsal aspect of the fingers/hand. At 3 months less than 30% of the patients experienced paresthesiae on fingertips I-IV and 15% on little fingertip. At 1 year, 10% of patients still complained of paresthesias on middle and little fingertips. CONCLUSIONS: Sensation improves statistically significantly within first 6 months after surgery, similarly to subjective patients' satisfaction assessed by the Levine questionnaire. Experience of paresthesiae in patients with CTS is not confined to the distribution of median nerve, although they are present most frequently at index and middle fingertips.