Design, physico-chemical properties and biological evaluation of some new N-[(phenoxy)alkyl]- and N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols as anticonvulsant agents.

A series of thirty N-(phenoxy)alkyl or N-{2-[2-(phenoxy)ethoxy]ethyl}aminoalkanols has been designed, synthesized and evaluated for anticonvulsant activity in MES, 6Hz test, and pilocarpine-induced status epilepticus. Among the title compounds, the most promising seems R-(-)-2N-{2-[2-(2,6-dimethylphenoxy)ethoxy]ethyl}aminopropan-1-ol hydrochloride (22a) with proved absolute configuration with X-ray analysis and enantiomeric purity. The compound is effective in MES test with ED50=12.92 mg/kg b.w. and its rotarod TD50=33.26 mg/kg b.w. The activity dose is also effective in a neurogenic pain model-the formalin test. Within high throughput profile assay, among eighty one targets, the strongest affinity of the compound is observed towards σ receptors and 5-HT transporter and the compound does not bind to hERG. It also does not exhibit mutagenic properties in the Vibrio harveyi test. Moreover, murine liver microsomal assay and pharmacokinetics profile (mice, iv, p.o., ip) indicate that the liver is the primary site of biotransformation of the compound, suggesting that both 22a and its metabolite(s) are active, compensating probably low bioavailability of the parent molecule.

Acid-base disorders in calves with chronic diarrhea.

The aim of this study was to analyze disorders of acid-base balance in calves with chronic diarrhea caused by mixed, viral, bacterial and Cryptosporydium parvum infection. We compared results ob- tained with the classic model (Henderson-Hasselbalch) and strong ion approach (the Steward model). The study included 36 calves aged between 14 and 21 days. The calves were allocated to three groups: I - (control) non-diarrheic calves, group II - animals with compensated acid-base imbalance and group III calves with compensated acid-base disorders and hypoalbuminemia. Plasma concentrations of Na+, K+, Cl-, C12+, Mg2+, P, albumin and lactate were measured. In the classic model, acid-base balance was determined on the basis of blood pH, pCO2, HCO3-, BE and anion gap. In the strong ion model, strong ion difference (SID), effective strong anion difference, total plasma concentration of nonvolatile buffers (A(Tot)) and strong ion gap (SIG) were measured. The control calves and the animals from groups II and III did not differ significantly in terms of their blood pH. The plasma concentration of HCO3-, BE and partial pressure of CO2 in animals from the two groups with chronic diarrhea were significantly higher than those found in the controls. The highest BE (6.03 mmol/l) was documented in calves from group II. The animals from this group presented compensation resulted from activation of metabolic mechanisms. The calves with hypoal- buminemia (group III) showed lower plasma concentrations of albumin (15.37 g/L), Cl (74.94 mmol/L), Mg2+ (0.53 mmol/L), P (1.41 mmol/L) and higher value of anion gap (39.03 mmol/L). This group III presented significantly higher SID3 (71.89 mmol/L), SID7 (72.92 mmol/L) and SIG (43.53 mmol/L) values than animals from the remaining groups (P < 0.01), whereas A(Tot) (6.82 mmol/L) were significantly lower. The main finding of the correlation study was the excellent relationship between the AGcorr and SID3, SID7, SIG. In conclusion, chronic diarrhea leads to numerous water-electrolyte disorders. Characterization of acid-base disturbance in these cases suggests that classic model have some limitations. This model can not be recommended for use whenever serum albumin or phosphate concentrations are markedly abnormal.

Invasiveness of Listeria monocytogenes strains isolated from animals in Poland.

Animals are important reservoir of Listeria monocytogenes, a pathogen causing serious infections in both humans and livestock. However, data on invasiveness of L. monocytogenes strains of animal origin is very scarce. Ability of 18 L. monocytogenes strains of animal origin to invade HT-29 cells was investigated. Plaque forming assay was used to assess invasiveness and ability of the pathogen to spread in the cell line. Almost 40% of L. monocytogenes strains were weakly invasive. It was shown that strains from serogroup 4b exhibited the highest invasiveness, whereas serogroup 1/2b consisted of strains of invasiveness below 0.0001%. Analysis of translated inlA and inlB gene sequences revealed no premature stop codons. Lineage-specific mutations in low invasive strains were identified within inlA and inlB sequences. Our results demonstrate high incidence of low invasive animal L. monocytogenes strains, which may be at least partly explained by unique point mutations in the InlA and InlB.

Winter blood values of selected parameters in a group of non-hibernating captive brown bears (Ursus arctos).

Bears undergo some significant changes reflected in blood values during winter season. The most significant are reduced urea and increased creatinine, by some authors considered to be physiological indicators of hibernation. Studied group of six captive brown bears (Ursus arctos) showed decreased activity in winter but were accepting food and walked outdoors. Blood parameters assessed in February 2011 revealed mean values of leucocytes and neutrophils as significantly lower, and creatinine significantly increased compared to captive and free living bears sampled during other seasons when bears are active.

Hepatitis E virus antibody prevalence in wildlife in Poland.

Hepatitis E is an important public health problem mostly in developing but occasionally also in industrialized countries. Domestic and wildlife animals are considered reservoirs of the hepatitis E virus (HEV). Since no information on the prevalence of autochthonous HEV infections in human and animal in Poland is available, the aim of the study was to investigate the HEV seroprevalence of different wildlife species as potential virus reservoirs in the country. No HEV antibodies were found in any of the sera collected from the red deer (Cervus elaphus), European bison (Bison bonasus), roe deer (Capreolus capreolus), elk (Alces alces), fallow deer (Dama dama), sika deer (Cervus nippon), Tatra chamois (Rupicapra rupicapra tatrica) or brown bear (Ursus arctos). HEV-specific antibodies were detected in 44.4% (95% CI 38.3-50.7) serum samples originated only from wild boars. The percentage of seropositive wild boars differed significantly between the provinces and was positively correlated with the wild boar density and rurality of the area. This study showed that HEV circulates among wild boar population in Poland, and this species should be considered as an important reservoir of the virus.

Genetic comparison of Campylobacter jejuni isolated from different cattle farms.

To compare the genotypes of Campylobacter jejuni, isolates of cattle origin were collected from 9 Polish farms and genotyped by ERIC-PCR. We identified 28 genotypes among the 43 C. jejuni isolates, and demonstrated high genomic diversity. The highest level of diversity was observed in strains isolated from stanchion-barn animals in opposition to those from the loose-housing system.

The influence of administration of biotin and zinc chelate (Zn-methionine) to cows in the first and second trimester of lactation on their health and productivity.

In cattle, the prevention of diseases might be possible using dietary methods, with nutritional optimization of feed rations. For years significant influence has been associated with the addition of biotin, methionine and zinc (each given individually, or as chelate - Zn-methionine). The aim of this study was to evaluate the influence of biotin or biotin + Zn-methionine additives on the health and performance of cows, in the first and second trimester of lactation. This study was carried out in 3 groups of cows, 30 animals in each group. In the first group cows were fed the usual fodder used on the farm. In the second group biotin at 10 mg/day/cow was added. In the third group both biotin at 10 mg/day/cow and Zn-methionine at 5 g/day/cow were added. The administration of biotin increased the milk yield and reduced the occurrence of retained placenta, as well as endometritis puerperalis. However, the high doses of biotin suppressed ovulation and oestrus symptoms in the investigated cows (low progesterone levels on days 15, 21 and 45 after calving). Zn-methionine in comparison to biotin had a lower effect on the milk yield in the cows. Moreover, its supplementation improved the milk content, as well as some of the blood parameters; it also decreased the number of somatic cells in milk. The concurrent administration of biotin and zinc-methionine seemed to be a good method for the prophylaxis of subacute mastitis and for the improvement of the high yielding dairy cows' productivity.

Induction of luciferase activity under the control of an hsp70 promoter using high-intensity focused ultrasound: combination of bioluminescence and MRI imaging in three different tumour models.

The in vivo temporal changes of luciferase activity were investigated under the control of an hsp70 promoter in three tumour models after the application of different intensities of high-intensity focused ultrasound (HIFU). Three cell lines, SCCVII, NIH3T3 and M21 were stably transfected with a plasmid containing the hsp70 promoter and luciferase reporter gene, and tumours were subcutaneously initiated into mice. At a size of 1300 ± 234 mm(3), the tumours were exposed to five intensities of continuous HIFU (802-1401-2157-3067-4133 W/cm(2)) for 20 sec. Bioluminescence and MR imaging were performed to assess luciferase activity and signal intensity changes in the tissue. The MRI scan protocol was pre- and post-contrast T1-wt-SE, T2-wt-FSE, DCE-MRI, diffusion-wt STEAM sequence, T2 relaxation time determination obtained on a 1.5-T GE MRI scanner. The NIH3T3 tumours showed the highest luciferase activity of 328.1 ± 7.1 fold at 24 h at a HIFU intensity of 3067 W/cm(2), the M21 tumours of 3.2 ± 0.6 fold 8 hours and the SCCVII tumours 2.9 ± 0.9 fold 4 hours post-HIFU at 2157 W/cm(2). The greatest increase in T2 signal intensity and T2 relaxation time of 20.7 ± 3.4% was seen in the SCCVII tumours. The highest contrast medium uptake of 10.1 ± 1.1% was noted in the M21 tumours, and 14.8 ± 1.9% in the SCCVII tumours. In all tumours, a significant increase in the diffusion coefficient was seen with increased HIFU intensity, the highest of which was 40.3 ± 4.1% in the SCCVII tumours. The three tumour cell lines stably transfected with the hsp70/luciferase gene showed differential luciferase activity, which peaked at different times after the application of HIFU and was dependant on tumour type and HIFU energy deposition.

Antimicrobial resistance of thermophilic Campylobacter spp. isolated from cattle in Poland.

Campylobacter species are among the most frequently identified bacterial causes of human gastroenteritis. Because Campylobacter spp. harbored by cattle can be transmitted to humans, in this study we investigated antimicrobial resistance of thermophilic Campylobacter isolated from cows. Our study included 150 strains of Campylobacter (143 strains of C. jejuni and 7 strains of C. coli) isolated from cows in South-Western Poland. The minimal inhibitory concentration (MIC) to ciprofloxacin, erythromycin, gentamicin and tetracycline were determined using the agar dilution methodology. All strains of C. coli were susceptible to all four drugs studied. The most frequently detected resistance of C. jejuni was to ciprofloxacin (26 strains 18.2%). Resistance to tetracycline was observed in 5 strains (3.5%). All strains of C. jejuni were susceptible to erythromycin and gentamicin.

Antiarrhythmic properties of some aroxyethylamine derivatives with adrenolytic activity.

A series of aroxyethylamines (1-10) have been previously evaluated for antihypertensive and adrenolytic properties. Of the derivatives tested, four (compounds 4, 7, 8 and 10) displayed significant antihypertensive activity and binding affinities for alpha- and beta-adrenergic receptors. As a continuation of our study, we present here the in vivo and in vitro antiarrhythmic activity of compounds 1-10, as well as their electrocardiographic properties. Only compounds 4, 7, 8 and 10 demonstrated strong antiarrhythmic activity in adrenaline induced arrhythmia after intravenous and oral administration. In addition, compounds 4 and 7 significantly decreased heart rhythm disturbances in arrhythmia induced by coronary artery occlusion and reperfusion. The pharmacological results and receptor binding studies suggest that the antiarrhythmic activity of the compounds tested may be related to their adrenolytic properties. Moreover, the presence of a methoxyphenylpiperazine moiety seems to be required for their pharmacological activity.

Genotype analysis of Campylobacter jejuni isolated from broilers in Poland.

Twenty-six Campylobacter jejuni strains isolated from poultry were analyzed by genotypic typing including ITS-profiling, REP- and ERIC-PCR. ITS-profiling revealed the presence of 8 different genotypes. Amplification of REP sequences by PCR gave similar results with 10 different genotypes. ERIC-PCR was found to be the most discriminatory for typing C. jejuni. As many as 13 different DNA patterns were obtained with this technique. Based on data obtained it was found that C. jejuni isolates recovered from broilers at the slaughterhouses in southwest Poland are characterized by a high degree of genetic heterogeneity.

The usefulness of the Phalen test and the Hoffmann-Tinel sign in the diagnosis of carpal tunnel syndrome.

Both the Phalen test and the percussion (Hoffmann-Tinel) test are considered to be the classic diagnostic tests for Carpal Tunnel Syndrome (CTS). Sensitivity of these tests, as given in the literature, ranges from 42 to 85% (Phalen) and from 38 to 100% (Hoffmann-Tinel), and specificity from 54 to 98% and from 55 to 100% respectively. The objective of this study was to evaluate sensitivity and specificity of both tests and to analyse the influence of such selected factors, such as patient's age and duration of symptoms. The clinical group consisted of 112 patients (147 hands) with CTS confirmed clinically and on nerve conduction studies. The control group of 50 patients (100 hands) was selected from hospital volunteers, who did not complain of any hand symptoms. Sensitivity and specificity of the Phalen test turned out to be respectively 85 and 89% and for the percussion test, 67 and 68%. There was no significant influence of patients' age upon the test results. Seventeen patients showed negative results for both tests, but in these individuals, the duration of symptoms was significantly longer than in the remaining group. These findings indicated essential diagnostic value for the Phalen test, but considerably smaller for the percussion test. In the diagnosis of long lasting syndromes, the usefulness of both tests is limited.

The results of operative treatment of fractures of the thumb metacarpal base.

The results of operative treatment of 21 patients with intraarticular fractures of the thumb metacarpal bone are presented. In 14 patients closed reduction was performed followed by percutaneous fixation with one or two K-wires through the metacarpal shaft to the trapezium. In five delayed cases, in which closed reduction was unsuccessful, open reduction and K-wire pinning was performed. After operation the hand and wrist were immobilized for four weeks. In two patients with Rolando-type fractures, an external fixator was used after closed reduction. Patients were followed-up for six months to three years (mean 1.5 years). Consolidation of fractures was achieved in all cases. Fourteen patients had no pain in the hand at final assessment, two complained of mild pain after activity, and another five complained of pain related to the weather. Grip strength of the affected hand ranged from 72% to 85% (mean 80%) of the expected standard value, matched for gender, age and dominant side. Full opposition of the thumb was achieved in all patients. Self-evaluation of the function of the hand expressed on an analogue scale, from 1 (normal hand function) to 5 (total disability), was from 1.1 to 1.5 (mean 1.2). Abduction of the affected thumb measured on x-ray ranged from 30 degrees to 50 degrees and it was 5 degrees-12 degrees less than in the unaffected hand. Secondary degenerative changes seen as narrowing of the trapeziometacarpal joint were observed in 16 patients. All patients returned to their previous occupations, among them five to hard manual work. None reported problems in daily activities. Our results suggest that closed reduction followed by percutaneous K-wire pinning is a valuable method of treatment for acute fractures. When treatment has been delayed an open operative approach should be considered.

ICAM-1 expression in autoimmune encephalitis visualized using magnetic resonance imaging.

The expression of leukocyte adhesion molecules in the intact brains of mice with experimental autoimmune encephalitis (EAE) was visualized by Magnetic Resonance Imaging (MRI) through the use of a new, target-specific MR contrast agent. Antibody-conjugated paramagnetic liposomes (ACPLs) were designed to achieve in vivo targeting of molecules expressed on vascular endothelium, while providing sufficient signal enhancement at these sites for detection by MRI. ACPLs targeted to intercellular adhesion molecule-1 (ICAM-1), an endothelial leukocyte receptor upregulated on cerebral microvasculature during EAE, were administered to diseased mice. Fluorescence microscopy confirmed that fluorescently-tagged ACPLs were localized to central nervous system (CNS) microvasculature in a pattern consistent with ICAM-1 upregulation described immunohistochemically. High resolution MRI of mouse brains ex vivo demonstrated that ACPL binding conferred significant enhancement of signal intensity (SI) as compared to control images. These results suggest that ACPLs can be used as MRI contrast agents to visualize specific molecules expressed on vascular endothelium during disease.

[Minor blunt abdominal trauma can be dangerous]. / Niebezpieczenstwa pozornie blahych zamknietych urazów jamy brzusznej.

Four cases with apparently mild abdominal trauma were presented. Finally, all but one were operated. On laparotomy ruptured spleen was found in two patients, the third had hematoma of the ileal mesentery. The fourth patient with subcapsular kidney hematoma was treated conservatively. All patients had initially denied any abdominal trauma. Sonography seems to be the most reliable and non-invasive investigation in making the diagnosis.

[Stab wound of the chest with penetration into abdominal cavity]. / Rana kluta klatki piersiowej drazaca do jamy brzusznej.

The case of the 33 year old woman with stab wound of the chest with penetration into abdominal cavity was presented. Due to injury mechanism the diagnostic thoracotomy was recommended. The operation confirmed the lung, diaphragm, spleen and kidney lesion. It was very interesting that patient with dangerous lesion of important organs had no clinical and radiological indications for emergency operation before.

VEGF gene delivery to muscle: potential role for vasculogenesis in adults.

Constitutive expression of VEGF after implantation of genetically engineered myoblasts into non-ischemic muscle led to an increase in vascular structures. Previously, effects of VEGF delivery to adult muscle have only been reported in ischemic tissues. The resulting vascular structures were reminiscent of those formed during embryonic vasculogenesis, rather than angiogenesis, sprouting from preexisting vessels. Initially, VEGF caused an accumulation of endothelial cells and macrophages, followed by networks of vascular channels and hemangiomas with locally high serum VEGF levels. No effects were evident in adjacent tissue or contralateral legs, where low serum VEGF was detected. These data suggest that the induction by VEGF of angiogenesis or vasculogenesis may be dose-dependent. Furthermore, VEGF expression must be carefully modulated, as overexpression is deleterious.

[The traumatic amputation of the forearm complicated by pneumocephalus]. / Amputacja urazowa przedramienia powiklana odma Sródczaszkowa.

The case of 37-year old man is reported who had traumatic amputation of the right forearm together with brachial plexus and cervical roots and third right rib fracture without pneumothorax. Due to a large damage of the limb replantation was dropped and only surgical elaboration of the wound was made. A few hours after the operation, dyspnoe and headache appeared. New x-ray picture showed right pneumothorax and pneumocephalus with continuing air shadow in cervical vertebral canal. In our opinion the air from pleura might go through cervical intramuscular space to the holes in dura after avulsed roots causing pneumocephalus.

[The use of the ulnar artery in hand replantation]. / Wykorzystanie tetnicy lokciowej w replantacji reki.

A method for restoring arterial circulation at replantation of the metacarpus with reversed ulnar artery is presented. It was employed in 31 years old patient who underwent replantation of the metacarpus with index, middle and ring finger. The little one was abandoned due to the vast damage. Great defect made end-to-end anastomosis not feasible. Reversed ulnar artery bypass served to restore arterial circulation without need for shortening of the metacarpals. Numerous presentations stressing arterial bypass advantages provoked our attempt to use this method. After half a year good functional and cosmetic result has been achieved.