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The goal of the present study was to investigate the daily rhythms of calcium, phosphate and 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂ D₃) in the blood serum of goats. Blood samples from six Girgentana breed goats were collected via an intravenous cannula inserted into the jugular vein at four-hour intervals over a 48-hour period (starting at 08:00 hours on day 1 and finishing at 04:00 on day 2). The serum concentration of calcium and phosphate was measured by photometric test and of 1,25-(OH)₂ D₃ by HPLC. All parameters were expressed as mean ± SEM. The one-way repeated measures analysis of variance (ANOVA) was used to determine significant differences. ANOVA showed a highly significant effect of time in all the parameters studied.. The application of the periodic model and the statistical analysis of the Cosinor enabled us to define the periodic parameters and their acrophases (expressed in hours) during the 2 days of monitoring: all the studied parameters exhibited diurnal acrophases, which were within 12:44 and 17:28 hours. The results obtained led us to reveal the existence of a daily rhythm for the parameters considered and their temporal physiological values are useful for their implications in the formulation of therapeutic and nutritional protocols in the goat.

The present investigation shows the antihyperglycaemic activity of aqueous extract of bark of Helicteres isora L. (100, 200 mg/kg b.w./p.o.) in streptozotocin (STZ) induced diabetic rats. Blood glucose levels, body weight, food and liquid intake were measured on every 5^th day over a period of 14 days. A single injection of STZ at a dose of 60 mg/kg b.w./i.p. elevated the glucose levels >240mg/dl after 5 days. Administration of H. isora at a dose of 100, 200 mg/kg/p.o. resulted in a significant (p

Phenylhydrazine (PHZ) and its derivatives were first given a medical application at the end of the 19^th century but with very little benefit. However, this compound seems to be very useful in models studying mechanisms of haemolytic anaemia. Phenylhydrazine induces a reactive oxygen species formation, peroxidation of lipids and oxidative degradation of spectrin in the membrane skeleton. PHZ-induced haemolytic injury seems to be derived from oxidative alternations to red blood cell proteins. This compound can modulate immune reactions.

In the present investigation, we studied the effect of aqueous green tea extract (GTE), alcoholic turmeric extract (ATE), and water-soluble Chitosan (WSC), individually/or in mixture, on the testicular tissue content of total cholesterol (TC), triglycerides (TG), phospholipids (PL), and thiobarbituric acid reactive substance (TBARS), in addition to nitric oxide (NO) in obese rats.
The testicular weight of the obese rats was increased more significantly than control; TC, TG, PL, TBARS and NO were significantly higher in the obese group. GTE reduced testicular weight and significantly reduced other estimated parameter. ATE significantly increased testicular weight, with apparent peritesticular vascular congestion. It significantly decreased all other studied parameters. WSC significantly increased testicular weight, with significant reduction of all other parameters. The mixture of the three drugs non-significantly decreased testicular weight, and significantly decreased other parameters, except NO, which was significantly more elevated than the obese control. We concluded that obesity induced a significant increase in testicular weight, in addition to TC, TG, PL, TBARS and NO, in comparison to the normal control subjects. An efficient protection against obesity-induced changes was achieved by each individual drug, while the mixture of GTE, ATE and WSC showed less protective potential than each individual drug.We here recommend the use of GTE, ATE in treating obesity-related testicular dysfunction and suggest that attention should be paid to the possible effect of WSC on the bioavailability of other concomitantly-used drugs and suggest a pertinent clinical benefit of both GTE and ATE.

This paper discusses new methods for 3-D processing of confocal microscope outputs - single optical cuts through an explored object. The method can model cell illumination by an external light source and is a next important step in the realistic displaying of cells. The computer program based on these methods can be run on a common PC.

Radiotherapy and chemotherapy are the basic approaches in cancer treatment, but these procedures are often associated with a number of undesirable side effects worsening the quality of life of the patient. In recent years a number of protective compounds capable of reducing or eliminating these side effects have been extensively investigated (for example: dexrazoxan, mesna, glutathion or N-acetylcystein). One of these compounds is amifostine (WR-2721), a broad-spectrum cytoprotective drug, selectively protecting normal tissues from the toxic effects of therapy, while the malignant tissues are subject to the anti-tumour effects of the treatment. In addition, several studies have revealed certain antimutagenic activities of amifostine making this agent potentially useful in the prevention of therapy-induced secondary malignancies. This article summarizes the information available on the antimutagenic and cytoprotective effects of amifostine and its effects also on the activity of the p53 tumour suppressor.

Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) is one of the highly toxic organophosphorus compounds misused as chemical warfare agents for military as well as terroristic purposes. It differs from other highly toxic organophosphates in its chemical structure and by the fact that the commonly used antidotes (atropine in combination with an oxime) are not able to sufficiently eliminate its acute toxic effects.
The neuroprotective effects of the newly developed oximes (K027, K048) or trimedoxime in combination with atropine (atropine, K027/atropine, K048/atropine and trimedoxime/atropine mixtures) on rats poisoned with tabun at a lethal dose (270 mg/kg i.m.; 120% of LD₅₀ value) were studied. The tabun-induced neurotoxicity was monitored using a functional observational battery and an automaticmeasurement of motor activity. The neurotoxicity of tabun was monitored at 24 hours and 7 days following tabun challenge. The results indicate that atropine alone is not able to protect rats from the lethal effects of tabun. Five non-treated tabun-poisoned rats and five tabun-poisoned rat treated with atropine alone died within 24 hours. On the other hand, atropine combined with all tested oximes allows most tabun-poisoned rats to survive within 7 days following tabun challenge. All three oximes tested combined with atropine seem to be sufficiently effective antidotes for a decrease in tabun-induced neurotoxicity in the case of lethal poisonings, although they are not able to eliminate tabun-induced neurotoxicity completely. Due to their neuroprotective effects, all the tested oximes appear to be more suitable oximes for the antidotal treatment of acute tabun exposure than the currently used oximes (pralidoxime, obidoxime, HI-6).

The present study was undertaken to evaluate the possibility of chiral discrimination in the release of enantiomers of ketoprofen (KT) in tablet form and, in turn, the bioavailability of the individual enantiomers, using the rabbit as a model. The enantiomeric concentration of KT in plasma was determined using a customized chiral HPLC analysis. First the plasma concentration-time profile was established for pure (±) KT in order to assess the extent of chiral discrimination. Subsequently the tablet formulation (Rhofenid-100mg) was administered, at a dose equivalent to 10 mg/kg, to assess the enantiospecific bioavailability of KT enantiomers in the rabbit following the same protocol as followed for the pure KT. In vivo studies revealed that the bioavailability of S-KT is higher than that of the R-enantiomer, after oral dosing with both KT-tablet and KT-pure. But the degree of chiral discrimination is more pronounced and more statistically significant in the case KT formulation as reflected by the enantioselective pharmacokinetic data. The observations presented in this article further emphasize the significance of differentiating between enantiomers of chiral drugs when assessing bioavailability and correlating efficiency with drug concentration. The study opens up a new avenue to the design of stereoselective dosage forms.

Evidence accrued over the last decade has supported an association between low serum selenium (Se) and increased incidence of prostate cancer in older men. Accordingly, questions and inquiry arose as to whether a dietary supplementation might afford protection, or delay disease progression. Indeed, a very large national study, Selenium and Vitamin E Cancer Prevention Trial (SELECT), to explore the potential benefits of a daily supplement of 200 microgram Se, or 400 I.U. of vitamin E, or both, is underway: the National Cancer Institute anticipates a total enrolment of 32,400 men and durations of 7 to 12 years for individual participants. It is remarkable that at the time of the trial's activation in 2001 nothing was known about the concentration of Se in the target organ or whether any Se in a dietary supplement found its way to the prostate gland. Later, our laboratory published the first benchmark values, which indicated that the prostate is reasonably well endowed with Se and that the concentration in one subject, who had undergone self-medication at 200 microgram Se per day, was about twice the average for the others. This review explores the ramifications of these and subsequent data for SELECT and other trials, together with observations on dose and general mechanisms of Se interference with the development of prostate cancer.

Quality control of the endoplasmic reticulum plays a critical role in protein folding, modification and modification of a secretory pathway. As endoplasmic reticulum chaperones, calreticulin and calnexin have similar substrate specificity and share several common features. Yet, surprisingly, mice bearing a disruption in the calreticulin gene die from a lesion in cardiac development and develop significant metabolic problems whereas calnexin-deficient mice are born alive with, yet not understood, neurological problems. Studies with calreticulin and calnexin gene knockout mice and calreticulin- and calnexin-deficient cell lines indicate that calnexin is unable to compensate for the loss of calreticulin and conversely, calreticulin cannot compensate for the loss of calnexin. Calreticulin or calnexin deficiency or reduction in the level of ERp57 protein (ERp57 heterozygote mice) leads to development of metabolic disorders as documented by sever changes serum lipids and carbohydrates composition in these animals. These observations indicate that calreticulin, calnexin and ERp57, in addition of being involved in maturation of glycoproteins in the endoplasmic reticulum, perform other distinct functions including affecting energy metabolism.

In the present study we have investigated the anticarcinogenic property of diallyl disulphide (DADS) on hepatic thiobarbituric acid reactive substances (TBARS) and antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in control, N-nitrosodiethylamine and diallyl disulphide treated rats. The levels of TBARS and activities of SOD and catalase were decreased in NDEA treated rats whereas GSH and GPx tended to increase in carcinogenic rats. Oral administration of DADS (60mg/kg body wt) tends to normalize these variables in liver. This clearly indicates that DADS could possess chemopreventive effects by modulating the oxidant-antioxidant status of the living system. However, the exact mechanism remains to be elucidated.

The radioprotective substances amifostine (WR-2721) and cystamine were tested in rats following their parenteral administration (i.p., i.m., and i.v.). Cystamine is more toxic than amifostine in mice as well as in rats. Amifostine was less toxic after intravenous injection. The radioprotective effects of WR-2721 (160 mg.kg^-1) and cystamine (40 mg.kg^-1) were not significant when they were administered parenterally 15 - 20 mins before lethal doses of whole body fission neutron irradiation in the thermal column of reactor VVR-S and 30-days lethality served as an integral criterion of postradiation injury to the rat body. The fission neutrons spectrum was characterized by mean energy 0.9-1.0 MeV with 30-40% fluency participation of moderate (E=0.1 MeV) neutrons. The contamination with gamma rays was 22-30 %; the dose rate of whole irradiation was within 0.3 to 0.8 Gy.min^-1.

Sequences available in public protein databases belonging to nucleolin or nucleolin-like proteins have been aligned using public domain software, in order to obtain relevant data regarding the degree of their conservation, which could be a reflection of the degree of conservation of the functions currently attributed to this protein. Nucleolin is known to be a nucleolar multifunctional protein, involved in different steps of pre-rRNA transcription and processing. Three domains are constantly present in all nucleolins, namely a series of acidic/serin (Ac/Ser) sequences, a number of RNA recognition motifs (RRM) and a region rich in glycin and arginin (GAR). The number of motifs present in each one of the three domains is variable. Furthermore, we have characterized in all nucleolins the presence of a bipartite consensus nuclear localization sequence (NLS). The only cases in which this sequence with a definite structure was not totally evident were in the yeast S. pombe (a possible monopartite structure) and in the protozoan T. thermophyla, in which it appears to be absent. Finally, we have constructed the phylogenetic tree of the 15 species investigated, taking exclusively the data regarding this protein. Interestingly, the tree obtained closely resembles the organization of these taxonomic groups throughout evolution, as it is presently known. We conclude that nucleolin is a highly conserved protein, whose gene was already present in an ancestor eukaryotic species, at an early stage of the evolutionary process, from which it has evolved very slowly. This is a reflection of the fundamental functions carried out by this protein, which were already fixed in the ancestor species.

The present study was performed to assess and compare the therapeutic efficacy of various oximes (methoxime, BI-6, HI-6) combined with benactyzine (BNZ) in cyclosarin (GF-agent)-poisoned mice and to evaluate the influence of pretreatment with PANPAL (pyridostigmine, benactyzine and trihexyphenidyl) on the effect of antidotal treatment in mice poisoned with the GF-agent. In the first part of our experiment, methoxime, BI-6 or HI-6 in combination with benactyzine were used for the treatment of GF-poisoned mice. In the second part of the experiment the animals were pretreated with PANPAL 60 min before the GF-agent challenge and then the oxime therapy was applied in the same time scheme as before. All the therapeutic regimens showed a protective ratio higher than 2 and significantly increased the LD₅₀ of GF-agent. The most efficacious oxime in decreasing of GF-agent toxicity was HI-6. PANPAL increased the protective ratios of all therapeutic regimens in comparison with administration of the oxime and BNZ alone. From the results obtained, the combination of pretreatment with PANPAL and following therapy with BNZ and HI-6 seems to be the most efficacious therapeutic regimen for treatment of GF-agent-poisoned mice.

Our research group has previously studied the role of melatonin in the immune system of birds and mice, finding that incubation with both pharmacological and physiological doses of melatonin augmented the activity of phagocytes from these animals, and that this activity was lowered in pinealectomized animals. Since melatonin is synthesized from the amino acid tryptophan, the aim of the present work was to determine whether the administration of tryptophan might affect the plasma levels of melatonin and the phagocytic activity of peritoneal macrophages over the course of a circadian cycle. The study animals were 14-week-old male Wistar rats. They were administered tryptophan orally in a daily single dose of 125 mg/kg at 19:00 h for 21 days. Prior to beginning this treatment, the circadian rhythms of plasma melatonin and phagocytic activity were evaluated under basal conditions over a 24-h period, taking blood and cell suspension samples each 2 hours during the light period (08:00-20:00) and each hour during the dark period (20:00-08:00), since it is during this latter period that the secretion of melatonin is maximum. The results showed that, under basal conditions, the rats' plasma melatonin levels and phagocytic activity peaked at 02:00. After the tryptophan administration, there were increases in plasma melatonin levels with respect to basal and control-group values, with a peak at 21:00, and in the phagocytic activity of the peritoneal macrophages, which peaked at 02:00. This suggests that the tryptophan administration stimulated melatonin synthesis, leading to increased and earlier peaking plasma levels of this hormone, and augmented the innate immune response carried out by the peritoneal macrophages as a result of the immunoregulatory action of melatonin.

Excitatory amino acids (EAA) represent major brain neurotransmitters. They are present in numerous neuronal systems and thus are involved in almost all aspects of normal and pathological brain activity. Changes in EAA transmission have been associated with the functional impairments characterizing major neurological disorders, including epilepsy and schizophrenia. There is also a suspicion that EAA systems underlie the neuronal death associated not only with acute CNS insults, such as in ischemia or post-traumatic lesions, but also with neurodegenerative diseases such as ALS, Huntington's disease and Parkinson's disease. The neurotoxicity of EAA, referred to as excitotoxicity, is presumably mediated primarily through an excess of EAA synaptic receptor stimulation. Indeed, overstimulation of the ionotropic NMDA or AMPA/kainate receptor subtypes has been shown to produce an intense membrane depolarisation and further a massive increase in intracellular calcium leading to cell damage. The extreme diversity and specific pattern of expression of EAA receptor subunits could account for the differential vulnerability of certain brain areas to such excitotoxic processes. In addition, it is now believed that besides abnormalities in receptor functioning or in release processes, alterations in EAA transmission may result from dysfunction of the EAA uptake system, which represents the mechanism for EAA removal from the synapse. From the five transporter proteins cloned, termed EAAT1-5, the primarily glial transporters EAAT1 and EAAT2 have been shown to mediate the bulk of EAA uptake in the brain and it has then been suggested that they play a major role in the prevention of excitotoxic processes. In this respect, the degeneration of motor neurons in ALS has been associated with altered expression or inactivation of EAAT2. Moreover, recent evidence has been provided that pharmacological alteration of glutamate transport can also induce astrocyte degeneration, as observed in neurodegenerative insults, but through a mechanism independent of stimulation of EAA receptors. Thus, one can obviously consider that these EAATs can represent a key target for further development of new neuroprotective agents.

Pentacyclic triterpenes are produced by arrangement of squalene epoxide. These compounds are extremely common and are found in most plants. There are at least 4000 known triterpenes. Many triterpenes occur freely but others occur as glycosides (saponins) or in special combined forms. Pentacyclic triterpenes have a wide spectrum of biological activities and some of them may be useful in medicine. The therapeutic potential of three pentacyclic triterpenes - lupeol, betuline and betulinic acid - is discussed in this paper. Betulinic acid especially is a very promising compound. This terpene seems to act by inducing apoptosis in cancer cells. Due to its apparent specificity for melanoma cells, betulinic acid seems to be a more promising anti-cancer substance than drugs like taxol.

Digital computers, which elevate the capacity of both individuals and human society, spread their possibilities widely in education. Software supports the teaching of physiology, anatomy, radiology, nursing, laboratory sciences and other fields of medicine. Existing learning programmes were assigned to drill and examined. The extension of the capacity of software graphics and penetration into research and practice makes it possible to use original documents and images and, therefore, to construct virtual reality which elevates effectiveness in facility training and the teaching of a creative approach among students. The Internet has been a major communication medium since the mid nineties. It brings greater democracy into the education process and makes it easier to admit data necessary in distance learning. Important databases (Web of Science, Medline etc.) have become part of ambitious university learning programmes; these databases are also available on the Internet. Despite technological progress in digital technology, many educational programmes contain only texts although web sites can be updated more frequently than printed textbooks. It is advantageous when a teacher helps and stimulates searching for excellent sites on the internet.

St. John's wort (Hypericum perforatum) has been used as a medical herb for over 2000 years. Over the past two decades, its application as a standardized plant extract for treating depression has undergone rigorous scientific investigation, and its effectiveness has been shown in studies comparing it with other commonly used antidepressants and placebos. Safety and tolerability studies have revealed that Hypericum preparations have better safety and tolerability profiles than synthetic antidepressants. The indications for St. John's wort preparations are mild or moderate depression. The mechanism of the antidepressant action of Hypericum extract is not fully known. The view of the chemical composition and pharmaceutical a toxicological properties of biologically active substances of Hypericum perforatum is the main purpose of this paper.

This paper concerns the functional architecture of the cell nucleus. Though it is DNA that carries our literal blueprint, our ancestry includes the nucleus itself, passed down through the 2.5 billion year evolutionary history of the Eukarya. Nuclear structure is presented here as two contrasting possibilities. In one case, the nucleus is envisioned as being built upon a backbone of protein filaments, analogous to the cytoskeleton. In this conceptual framework, the chromosomes are considered to passively adopt locations that are dictated by their attachments to the imagined skeleton, and their activity is postulated to be the result of such attachments. In the other case, nothing in the architectural design of the nucleus is more deterministic than the chromosomes themselves, and their activity. Here, gene activity is thought to be based on the binding of DNA sequence-specific activator or silencing proteins that arrive at their target sites by diffusion. Moreover, additional elements of nuclear structure are viewed as arising from the very action of the genes themselves, such as nascent mRNAs packaged into ribonucleoprotein particles as well as large, heterotypic molecular machines involved in RNA processing. In this case, termed the "genome-centric model", the observed structure of the nucleus is not based on some underlying, prefabricated skeleton, but is in fact the actual ongoing cytological manifestation of genes in action. Upon careful analysis of all the evidence, the genome-centric model enjoys favor at the present time. However, we are still in kindergarten days in our understanding of the cell nucleus and, as always, it is wise to keep an open mind. New advances in biophysical, nanotechnology and systems biology approaches to nuclear architecture encourage us to believe that we may soon graduate into the gymnasium - if not university, level of our nuclear education. Viewed metaphorically as art (as in the playful title of this paper), we understand the paint at every atom of pigment on the palette - i.e., the covalent genome, the DNA. It is the final, creative work as applied to the gene expression canvas itself that we must now strive to know.

The liver is the main organ involved in the metabolism of xenobiotic (foreign) compounds. The responsible enzymatic systems are the cytochromes P450 (mixed function oxidases or phase I reactions) and enzymes coupling larger water soluble groups to the substrate (phase II reactions). Especially during phase I reactions, highly reactive metabolites can be formed capable of interacting with DNA and causing mutations. On the other hand reactive xenobiotics may be detoxified. Therefore, the primary parenchymal liver cell (hepatocyte) appears to be the optimal and most reliable in vitro system for the determination of mutagenicity/genotoxicity. Since however, primary hepatocytes are proliferatively quiescent, a culture system had to be developed allowing for proliferation enabling the determination of induced changes at the chromosomal level. This paper summarizes the special features of primary hepatocytes, the findings on in vitro proliferation and the application of hepatocyte cultures for in vitro and ex vivo/in vitro toxicological testing.

The aim of our work was to prepare part of the input data for a computational biomechanical model of both the active and passive elements of the tunica media of an aortic aneurysm. We analyzed tissue samples of the anterior wall of the normal, atherosclerotic and aneurysmatic subrenal abdominal aorta. We assessed the proportions of smooth muscle cells, elastin and collagen in histological sections of these samples and studied the morphological characteristics of the elastin network in the tunica media. Selected photomicrographs were studied, representing relatively well preserved areas without artifacts, ruptures, corrupted integrity of the tunica media or total elastinolysis. A new method was introduced for the assessment of structures formed by elastin membranes and fibres, using the fast Fourier transform (FFT) technique. The image was transformed into reciprocal (Fourier) space and the method made use of the fact that the FFT was very sensitive to the orientation distribution of thresholded elastin morphology. The results of this comparative study, obtained from selected samples from 24 patients, revealed that the percentage values of the constituents of the arterial wall can not distinguish between the preserved segments of normal, atherosclerotic or aneurysmatic aorta. The results of the Fourier analysis proved that the FFT provided an efficient method for evaluating cross sections of the elastin membranes and fibres, reflecting their anisotropy. The shape of the power spectrum of elastin was a simple pattern, whose description was quantified by the shape of its polar coordinates histogram. We discuss the methodological difficulties and biomechanical implications of our work as well compare it to other methods of elastin analysis.

We evaluate the possibility of using insects as a haematological biomodel and we test phytoestrogen isoflavanoid, genistein, in Schistocerca gregaria, Periplaneta americana and Dysdercus cingulatus. Various reactions of haemocytes were found in these three species, both stimulation and inhibition of haemocyte concentration. The observed data reflected well the possible effects of soy products described in published studies on human subjects and it seems that future studies on the sensitivity of insect haemocytes could lead to an alternative haematological biomodel.

The purpose of this preliminary, double-blind, placebo-control study was to evaluate the effect of GaAlAs diode laser on wound healing and pain reduction in patients after extraction of impacted lower third molars by infrared thermography. Material and methods: The study population of two patients was divided into group A treated by GaAlAs diode laser with a wavelength 830 nm and maximal output power of 100 mW and group B treated by placebo laser. Therapeutic Schedule: The energy density per point was 12 J, treatment time 2 minutes, the total energy density for one treatment session was 36 J. Treatment intervals were 10 minutes after extraction, 1 and 3 days after extraction. Patients in group B were treated with a placebo probe in the same schedule. Patients evaluated the level of pain and swelling on 100 mm Visual Analog Scale. Thermographic measurements were performed by ThermaCAM™ SC 2000 before extraction, 30 minutes after extraction and on the 1^st, 3^rd, 5^th, 8^th days. Results: The patient treated by active laser reported more pain and swelling during the first week after tooth extraction than the patient treated by placebo laser. However, the comparison of thermograms of patients treated by placebo and active laser showed the acceleration of wound healing after extraction in the patient treated with GaAsAl diode laser. Conclusion: The treatment by GaAlAs diode laser, 830 nm and total energy density for one treatment session 36 J had a stimulation effect on the healing process but did not lead to reduction of pain and swelling in the patient after dental surgery.