The investigation of interspecies diversity of erythrocyte aggregation properties by two different photometric methods in four animal species.

Among the haemorheological parameters, red blood cell (RBC) aggregation shows the largest interspecies diversity, and often controversial data can be found in the literature, besides the methodology-dependent issues. In this present investigation, we compared four experimental/laboratory animal species' RBC aggregation by two different photometric methods for better revealing the differences. Blood samples (K3-EDTA, 1.5 mg/ml) were taken from female animals: 16 inbred mice (Mus musculus, cardiac puncture), 15 outbred rats (Rattus norvegicus, caudal caval vein puncture), 15 beagle dogs (Canis canis, cephalic vein) and 23 juvenile pigs (Sus scrofa domesticus, medial saphenous vein). Haematological parameters (microcell counter) and RBC aggregation (light transmission and syllectometry-laser backscatter methods) were determined within 2 h after sampling. Describing the first 5-10 s of the aggregation process, additional parameters were calculated out of the syllectometric raw data. Standardized difference was calculated to determine the sensitivity of the two devices. Parameters describing the extent and magnitude of red blood cell aggregation showed the lowest values in the rat and the highest in the pig and canine blood. In turn, parameters describing the kinetics of aggregation showed the lowest values in the mouse and the highest in the rat. The standardized difference values for the laser backscattering method were 2-4 times larger vs. the light transmission one. The magnitude of the differences was not consequent in the aggregation parameters. These comparative results show that the laser backscattering method can detect the RBC aggregation differences between the investigated species more sensitively than the light transmission method.

Influence of peripheral vascular calcification on efficiency of screening tests for peripheral arterial occlusive disease in diabetes--a cross-sectional study.

AIMS: Pulse palpation and ankle brachial index are recommended to screen for peripheral arterial occlusive disease in people with diabetes. However, vascular calcification can be associated with false negative tests (arteriopathy present despite normal screening tests). We therefore studied the impact of peripheral vascular calcification on the performance of these tests. METHODS: This cross-sectional study included 200 people with diabetes at high risk of cardiovascular disease. The main exclusion factor was an estimated glomerular filtration rate < 30 ml/min. Peripheral arterial occlusive disease was diagnosed by colour duplex ultrasonography and peripheral vascular calcification scored by computed tomography scan. We measured sensitivity, specificity, predictive values, accuracy and likelihood ratios of pulse palpation and ankle brachial index, and looked for the impact of calcification on false negative tests (arteriopathy present despite normal screening tests). RESULTS: Ankle brachial index alone had poor sensitivity and negative predictive value and high negative likelihood ratio. Pulse palpation had higher sensitivity and negative predictive value. An abnormal pulse palpation, defined by weak or missing pulses, combined with an abnormal ankle brachial index, had the highest sensitivity and negative predictive value (92.3 and 89.8%, respectively). Vascular calcification score was higher in patients with false negative tests, for both pulse palpation and ankle brachial index (P < 0.0001 for all). Ankle systolic blood pressure was higher in patients with false negative tests for pulse palpation (P = 0.004). CONCLUSIONS: Below-knee vascular calcification gave a high rate of false negative results for ankle brachial index. Refined pulse palpation combined with ankle brachial index remained the best strategy to screen for peripheral arteriopathy.

A review of UVB-mediated photosensitivity disorders.

Photosensitivity to UVB is a prominent feature of a small number of congenital skin disorders. In addition UVB may also contribute to the action spectrum of a number of acquired photosensitivity syndromes. The gene mutations underlying the genetically inherited disorders have largely been identified and have provided insights into DNA repair pathways. The pathomechanisms for the acquired disorders are still largely undefined. Few therapeutic options are available so management of all these disorders still relies on rigorous photo-protection.

Cestode genomics - progress and prospects for advancing basic and applied aspects of flatworm biology.

Characterization of the first tapeworm genome, Echinococcus multilocularis, is now nearly complete, and genome assemblies of E. granulosus, Taenia solium and Hymenolepis microstoma are in advanced draft versions. These initiatives herald the beginning of a genomic era in cestodology and underpin a diverse set of research agendas targeting both basic and applied aspects of tapeworm biology. We discuss the progress in the genomics of these species, provide insights into the presence and composition of immunologically relevant gene families, including the antigen B- and EG95/45W families, and discuss chemogenomic approaches toward the development of novel chemotherapeutics against cestode diseases. In addition, we discuss the evolution of tapeworm parasites and introduce the research programmes linked to genome initiatives that are aimed at understanding signalling systems involved in basic host-parasite interactions and morphogenesis.

A review of UVA-mediated photosensitivity disorders.

A number of skin conditions are characterised by photosensitivity to UVA. Some of these are exclusively UVA-mediated conditions, while others include UVA in the action spectrum which also include UVB and/or visible light. This review aims to describe this diverse range of conditions for non-dermatologist scientists with an interest in this topic. As such, clinical details, including treatments, are brief and succinct. Recent advances in understanding the pathogenesis of these conditions is highlighted.

Changes in a nanoparticle's spectroscopic signal mediated by the local environment.

Using a first-principles theoretical model the adsorption of a methyl radical on different sized silver nanoparticles is compared to the adsorption of the same radical on model surfaces. Calculations of our structural, dynamical and electronic properties indicated that small changes in the local environment will lead to small changes in infrared (IR) wavenumbers, but in dramatic changes in the IR signal. Our calculations indicate the lower the adsorption site coordination, the higher is the signal strength, suggesting that small changes in the electronic charge distribution will result in bigger changes in the polarizability and hence in the spectroscopic signal intensity. This effect explains, among others, the signal magnification observed for nanoparticles in surface enhanced Raman spectroscopic (SERS) experiments.

Size effects on silver nanoparticles' properties.

In this work a systematic study of the dependence of the structural, electronic, and vibrational properties on nanoparticle size is performed. Based on our total energy calculations we identified three characteristic regimes associated with the nanoparticle's dimensions: (i) below 1.5 nm (100 atoms) where remarkable molecular aspects are observed; (ii) between 1.5 and 2.0 nm (100 and 300 atoms) where the molecular behavior is influenced by the inner core crystal properties; and (iii) above 2.0 nm (more than 300 atoms) where the crystal properties are preponderant. In all considered regimes the nanoparticle's surface modulates its properties. This modulation decreases with the increasing of the nanoparticle's size.

Chronic administration of quercetin induces biomechanical and pharmacological remodeling in the rat coronary arteries.

Acute dilation brought about by the dietary flavonoid quercetin in coronary arterioles has been described earlier, but no information is available on its chronic effects. Male Wistar rats (body weight about 190 g) were divided to two groups: the quercetin-treated group (n=22) had quercetin supplementation of approximately 30 mg/kg/day, whereas the control group (n=20) had none. After eight weeks of treatment, intramural coronary arterioles with identical passive diameters (178+/-14 microm and 171+/-9 microm) were prepared and their biomechanics and pharmacological reactivities were tested using pressure arteriography ex vivo. The spontaneous tone of quercetin-treated arteries was higher (16.5+/-1.9 % vs. 12.9+/-0.9 %), which resulted in a reduced lumen size (144+/-9 microm vs. 167+/-12 microm), thicker vascular wall (22.6+/-1.8 microm vs. 17.4+/-1.6 microm) and decreased tangential wall stress (16.8+/-1.1 kPa vs. 20.5+/-1.6 kPa) in supplemented animals (in spontaneous tone at 50 mm Hg, p<0.01 in all these comparisons). Elevated basal NO release resulted in increased endothelial dilation in quercetin-treated animals, especially at higher intraluminal pressures (10.8+/-2.5 % vs. 5.7+/-1.3 % at 70 mm Hg, p<0.01). We found remodeling of the geometry of coronary arterioles to ensure higher dilatory reserve and nitrogen monoxide production, as well as lowered elastic stress of the vessel wall.

Comparison of intestinal toxic effects of platinum complexes: cisplatin (CDDP), carboplatin (CBDCA), and iproplatin (CHIP).

The biochemical background of the intestinal side effects of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (CBDCA) and cis-diisopropylamine-trans-dihydroxy-dichloro platinum (IV) (CHIP) was compared with those of cis-diamminedichloroplatinum (II) (CDDP). Biochemical investigations were carried out on mucosal cells isolated by a combined chemical-mechanical method from the total length of the small intestine. After treatment with single, equitoxic doses of Pt analogues, the activities of thymidine kinase (TK) EC 2.7.1.21, sucrase (SUC) EC 3.2.1.26, maltase (MAL) EC 3.2.1.20, and protein content showed dose-dependent decreases, whereas the activity of alkaline phosphatase (AP) EC 3.2.1.20 increased slightly. The nadir of enzyme activity changes occurred 24-48 h after treatment. For the regeneration of the mucosa more than 96 h was necessary. Of the platinum analogues studied, CHIP proved to be the most toxic to the small intestine. While the highest doses of CDDP and CBDCA (0.66 x LD50) caused significant but less than 50% decreases in TK, SUC, MAL, and protein content (PROT), the CHIP doses needed for 50% reduction were between 0.44-0.66 x LD50.

Decomposition of cisplatin in aqueous solutions containing chlorides by ultrasonic energy and light.

Decomposition of cisplatin in an aqueous 0.15 M chloride solution by diffuse daylight, by monochromatic light, and by ultrasonic energy was studied using a new HPLC method. The relative sensitivity of cisplatin to light copies the curve of the absorption spectrum of cisplatin with maximum at ca. 300 nm; however, any light below 500 nm must be avoided. Sonication also leads to a rapid decomposition of cisplatin. Irradiation by diffuse daylight or sonication of the cisplatin solutions for 5 min leads to ca. 1% amminetrichloroplatinate(II). Using HPLC analysis with diode-array spectrophotometric detection, the main decomposition product was identified as amminetrichloroplatinate(II).

[Value of ultrasonography in the diagnosis of bladder tumors]. / Der Wert der Ultrasonographie in der Harnblasentumordiagnostik.

The authors have compared the value of transabdominal, transrectal and intravesical ultrasonography in 100 patients with carcinoma of the bladder. They have also compared the pathological stage, determined at operation or post mortem, with the "ultrasound" stage. Transabdominal examination resulted in agreement in 61% cases, transrectal 69% and intravesical in 92%. In the authors' opinion, transabdominal ultrasonography is suitable for general orientation. It can determine the size and position of the tumour. Transrectal examination is particularly valuable if, for any reason, it is impossible to perform cystoscopy. It is also valuable for the examination of tumours localised at the bladder base. Intravesical sonography demonstrated the tumour in every case. During this examination, changes in the elasticity and distensibility of the bladder due to tumour and changes in the bladder volume can be determined. Intravesical ultrasonography carried out at the same time as cystoscopy is a rapid and highly practical procedure, which ideally supplements cystoscopy. At present it is the best method for demonstrating infiltration of the bladder wall.

HPLC analysis of platinum cytostatics.

High performance liquid chromatography (HPLC) with diode array detector (DAD) was applied for the separation of platinum cytostatics (cisplatin, carboplatin and oxo-carboplatin). Their stabilities were studied in water and the influence of chloride anions, pH, temperature and time was discussed and rate constants of the aquation reactions at different conditions were calculated. Ligand exchange reactions cisplatin----carboplatin were evaluated using HPLC-DAD system. Detection limits for all studied cytostatics were determined and extraction recoveries for carboplatin in clinical samples (serum) were demonstrated for a wide range of concentrations together with the relative standard deviations. The solid-phase extraction procedure was recommended for clinical sample analysis represented by a model mixture and real patients' samples.

Antitumor activity and cross-resistance studies with Pt-ascorbato complexes.

Two ascorbatoplatinum complexes, cis-diammineascorbatoplatinum(II) (AMA) and cis-bis(ascorbato)-trans-diaminocyclohexaneplatinum(II) (CHA), were tested for antitumor activity in vivo on P388 leukemia and in vitro in suspension culture and soft agar assay. Sensitive line of L1210 and sublines with resistance induced against cis-diamminedichloroplatinum(II) (DDP) and two derivatives of trans-1,2-diaminocyclohexane (DACH) were used for the in vitro tests. DNA synthesis inhibition in both sensitive and resistant cells was tested. The results are compared with DDP and DACH-Pt(II)-4-carboxyphtalate (TMA). Both tested complexes proved their antitumor activity in our experimental systems. The CHA complex was more effective than AMA and its effectiveness is comparable with that of DDP and TMA. Cross-resistance was found between DDP and AMA as well as TMA and CHA. There was no cross-resistance between DDP versus CHA, and TMA versus AMA.

Evaluation of side effects of platinum complexes (CDDP, CBDCA, CHIP) on rat bone marrow.

The in vivo toxic actions of cis-dichloro-1, 1-cyclo-butane-dicarboxylate platinum (II): carboplatin (CBDCA), cis-diisopropyl-ammine-transdihydroxy-dichloro platinum (IV) and iproplatin (CHIP) were compared with those of cis-diamminedichloroplatinum (II): cisplatin (CDDP) on rat bone marrow. To elucidate the biochemical basis of side effects of platinum analogs, the protein and DNA content, thymidine kinase (TK) EC 2.7.1.21 activity and cellularity (MNC) were measured from the femoral bone marrow at 48 hours after i.v. single injection of these three compounds using equitoxic doses as fraction of LD50 (CDDP: 9, CHIP: 50, CBDCA: 80 mg/kg). Dose response studies showed that each drug depressed in dose dependent fashion the cellularity, DNA content and TK activity. As the I50 values indicated, the CHIP caused the most toxic effect in the bone marrow and the influence of CBDCA was the least. The nadir of biochemical alterations was observed 24-48 hours after drug administration. The recovery of bone marrow was completed 96 hours after the treatment.

[The method of demonstrating phenoloxidase]. / Ein Beitrag zur Methodik des Phenoloxidasenachweises

It is reported on the evidence of phenoloxidase containing cells (=POZ) under various experimental conditions in as well spleen and small gut of white rats as small gut and skin of rabbit. A modified technic is described which gives a shortened incubation time and a regulary pigmentation of the reactive cells. POZ are demonstrable between pH = 6.2 and 8.0.

Testicular germ cell tumours. Current problems of histogenesis and classification.

Testicular germ cell tumours, owing to their variety in biological behaviour and morphological appearance, claim a place of their own in clinical oncology and tumour research. Much of the histogenesis has remained unexplained, as reflected by the different systems of pathological classification. This report sums up, on basis of the literature, the current pathologic views on the question of testicular tumour genesis. Data obtained from immune histochemical examinations, animal experiments, ultrastructure studies, together with clinical observations, suggest that differentiation of the carcinomatous stem cells are apt to produce forms, transitional between seminomatous and non-seminomatous types of tumour. The possibility to set up a uniform, clinically appropriate nomenclature depends on the progress in histogenetic knowledge.

Papillary serous cystadenoma of the testis.

A case is presented of a 50-year old man with a unilocular cystic intratesticular tumour exhibiting the morphological features demanded from WHO for the diagnosis of serous papillary cystadenoma of the ovary. Keratin filaments could be demonstrated in the cyst lining and papillae covering cells by means of PAP-technique; AFP and SP-1 were lacking. The epithelial cells of the tumour showed a lectin binding pattern (WGA, UEA-I, PNA, Con A, PSA, LCA, RCA) different from the epithelium of rete testis and epididymis. We intend to classify our tumour as the male analogue of the respective ovarian growth.

[Determination of cis-diamminedichloroplatinum compound toxicity in pigs from the viewpoint of pathomorphology]. / Overování toxicity cis-diammin-dichloroplatnatého komplexu u prasat z hlediska patomorfologického.

The study is a part of the clinical testing of the cytostatic preparation PLATIDIAM --Lachema with cis-diammine-dichloroplatinum complex (cis/DDP) as an active ingredient. The organs and tissues of 18 test pigs weighing 31 to 55 kg were subjected to the patho-morphological examination. The animals had been given experimentally the test cytostatic preparation Platidiam at a rate of 2.5 and 4.0 mg cis-DDP per kg 1. w. with and without hydration of their organisms. Severe changes were recorded in the kidneys of the pigs given the toxic doses of cis-DDP (4 mg/kg l. w.). The most frequent finding was that of cylindrical protein blocks in renal tubules combined with hyalinization of tubule cells. Optical microscopy of marrow showed vacuolization of epithelium and peeling off of epithelium layers. In some cases the dystrophic changes in renal tubules even led to necrotization of epithelium. No such changes were observed in the remaining animals given the therapeutic doses (2.5 mg/kg l. w.) nor in the controls. The findings on other organs cannot be associated with the toxicity of cis/DDP.