Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic ß-cells.

Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of ß-cell dysfunction induced by glucotoxicity. We employed three pancreatic ß-cell lines, namely INS-1, 1.2B4, and NIT-1, as well as a streptozotocin-induced diabetes rat model. We demonstrate that after high glucose treatment, RAP1 is increased, probably through induction by AKT, allowing RAP1 to shuttle from the nucleus to the cytoplasm and activate NF-κB signaling. Furthermore, non-enzymatic post-translational modifications of RAP1, such as advanced glycation end products and carbonylation may affect the function of RAP1, such as activation of the NF-κB signaling. Taken together, we showed that RAP1 is a new player in the mechanism of glucotoxicity in pancreatic ß-cells.

Morphological defects of epididymal spermatozoa in male roe deer (Capreolus capreolus) during the reproductive season.

The aim of this study was to analyse the morphology of the epididymal spermatozoa of male roe deer obtained postmortem at the beginning (May), peak (July/August) and the end (September) of the reproductive season. Spermatozoal abnormalities were divided into major (associated with impaired fertility) and minor (not associated with impaired fertility) defects. The highest percentage of abnormal spermatozoa was observed in May (17.78±1.88%), with a much higher proportion of major (12.35±1.11%) than minor defects (5.43±1.59%) being observed. The percentage of abnormal spermatozoa was lowest during the peak of the reproductive season (4.97±1.13%), with the proportion of major (2.68±0.78%) and minor defects (2.28±0.45%) being comparable during this period. The percentage of abnormal spermatozoa increased again in September (11.05±1.60%), with the major defects (6.15±1.04%) slightly surpassing the minor defects (4.90±0.77%); however, total abnormalities still remained lower than those found in May. These differences were statistically significant, with the exception of the difference in minor defects between the pre-rut and post-rut periods. These results indicate that the best period to collect epididymal spermatozoa from roe deer postmortem is the peak of the reproductive season (July/August); however, they can also be recovered at the end of the reproductive season (September), as the percentage of major defects is relatively low at this time. This study provides the basis for further research to determine optimal methods for the storage and cryopreservation of epididymal spermatozoa in this species.

Reducing monitoring costs in industrially contaminated rivers: cluster and regression analysis approach.

Monitoring contamination in river water is an expensive procedure, particularly for developing countries where pollution is a significant problem. This study was conducted to provide a pollution monitoring strategy that reduces the cost of laboratory analysis. The new monitoring strategy was designed as a result of cluster and regression analysis on field data collected from an industrially influenced river. Pollution sources in the study site were coal mining, metallurgy, chemical industry, and metropolitan sewage. This river resembles those in other areas of the world, including developing countries where environmental monitoring is financially constrained. Data were collected on variability of contaminant concentrations during four seasons at the same points on tributaries of the river. The variables described in the study are pH, electrical conductivity, inorganic ions, trace elements, and selected organic pollutants. These variables were divided into groups using cluster analysis. These groups were then tested using regression models to identify how the behavior of one variable changes in relation to another. It was found that up to 86.8% of variability of one parameter could be determined by another in the dataset. We adopted 60, 65, and 70% determination levels () for accepting a regression model. As a result, monitoring could be reduced by 15 (60% level) and 10 variables (65 and 70%) out of 43, which comprises 35 and 23% of the monitored variable total. Cost reduction would be most effective if trace elements or organic pollutants were excluded from monitoring because these are the constituents most expensive to analyze.

Endogenous carbon monoxide (CO) as a modulating factor of molecular biological clock in the hypothalamic structures involved in light transmission in pig and wild boar hybrid during long and short day season.

Mature males of a wild boar-pig crossbreed, during the long and short day season, were used for the study which demonstrates that the chemical light carrier CO regulates the expression of biological clock genes in the hypothalamus via humoral pathways. Autologous blood with experimentally elevated concentrations of endogenous CO (using lamps with white light-emitting diodes) was infused into the ophthalmic venous sinus via the right dorsal nasal vein. Molecular biology methods: qPCR and Western Blot were used to determine the expression of genes and biological clock proteins. The results showed that elevated endogenous CO levels, through blood irradiation, induces changes in genes expression involved in the functioning of the main biological clock located in suprachiasmatic nuclei. Changes in the expression of the transcription factors Bmal1, Clock and Npas2 have a similar pattern in both structures, where a very large decrease in gene expression was shown after exposure to elevated endogenous CO levels. The changes in the gene expression of PER 1-2, CRY 1-2, and REV-ERB α-ß and ROR ß are not the same for both POA and DH hypothalamic structures, indicating that both structures respond differently to the humoral signal received. The results indicate that CO is a chemical light molecule whose production in an organism depends on the amount of light. An adequate amount of light is an essential factor for the proper functioning of the main biological clock.

K(h)α1,2 x-ray hypersatellite line broadening as a signature of K-shell double photoionization followed by outer-shell ionization and excitation.

We propose a novel approach for the theoretical analysis of the photoinduced high-resolution K(h)α(1,2) x-ray hypersatellite spectra, which allows us to obtain reliable values of lifetimes of the doubly K-shell ionized states and fundamental information about the relative role of K-shell double photoionization (DPI) mechanisms. It is demonstrated for the first time that the K(h)α(1,2) hypersatellite natural line broadening observed for selected metal atoms with 20 ≤ Z ≤ 30 can be well reproduced quantitatively by taking into account the influences of the open-shell valence configuration (adopted from predictions of the band-structure method) and the outer-shell ionization and excitation following the DPI process.

Electromagnetic field of extremely low frequency has an impact on selected chemical components of the honeybee.

The electromagnetic field (EMF) is an environmental factor affecting living organisms. The aim of this study was to demonstrate the effect of an extremely low frequency electromagnetic field (ELF-EMF) on selected chemical components of the honeybee (Apis mellifera L.) using Fourier Transform Infrared (FTIR) spectroscopy. The FTIR method provides information on the chemical structure of compounds through identification and analysis of functional groups. The honeybees were treated with EMF at a frequency of 50 Hz and magnetic induction of 1.6 mT for 2, 6, 12, 24 and 48 hours. Analysis of FTIR spectra showed that EMF exposure longer than 2 hours induced changes in the structure of chemical compounds, especially in the IR region corresponding to DNA, RNA, phospholipids and protein vibrations, compared to control samples (bees not EMF treated). The results confirm the effect of EMF on bees depending on the duration of exposure.

Serum progesterone concentrations on the day of oocyte retrieval above 9.23 ng/ml may predict ovarian hyperstimulation syndrome risk in in vitro fertilized patients.

The aim of our study was to evaluate serum progesterone levels on the day of oocyte retrieval as a promising biomarker inorder to evaluate the risk of ovarian hyperstimulation syndrome in a group with controlled ovarian hyperstimulation protocols using either gonadotropin antagonists or agonists (GnRH), compare with a natural cycle control group. Patients were divided into 3 groups (148 patients in total): control group in the natural cycle, patients treated with GnRH agonist and patients treated with GnRH antagonist. When we compared both controlled ovarian hyperstimulation (COH) protocol groups with the control group, we found statistically higher levels of progesterone in patients after COH (control versus long protocol group: 1.43 ± 1.28 ng/ml versus 8.95 ± 5.95 ng/ml; P < 0.001; control versus GnRH antagonist group: 1.43 ± 1.28 ng/ml versus 7.18 ± 5.13 ng/ml; P < 0.001). According to receiver operating characteristic (ROC) analysis, the level of serum progesterone on the day of oocyte retrieval, above which the risk of ovarian hyperstimulation syndrome (OHSS) is associated with a more than fourfold higher risk (OR 4.24; 95% CI 2.6 - 6.9) was found to be 9.23 ng/ml, with AUC: 0.896, P = 0.026 (95% CI 0.845 - 0.947). Progesterone level on the day of oocyte retrieval may be used as an additional sensitivity marker in treatment of early forms as well by freezing of embryos in prevention of late forms of OHSS.

The operational window of carbon nanotube electrical wires treated with strong acids and oxidants.

Conventional metal wires suffer from a significant degradation or complete failure in their electrical performance, when subjected to harsh oxidizing environments, however wires constructed from Carbon Nanotubes (CNTs) have been found to actually improve in their electrical performance when subjected to these environments. These opposing reactions may provide new and interesting applications for CNT wires. Yet, before attempting to move to any real-world harsh environment applications, for the CNT wires, it is essential that this area of their operation be thoroughly examined. To investigate this, CNT wires were treated with multiple combinations of the strongest acids and halogens. The wires were then subjected to conductivity measurements, current carrying capacity tests, as well as Raman, microscopy and thermogravimetric analysis to enable the identification of both the limits of oxidative conductivity boosting and the onset of physical damage to the wires. These experiments have led to two main conclusions. Firstly, that CNT wires may operate effectively in harsh oxidizing environments where metal wires would easily fail and secondly, that the highest conductivity increase of the CNT wires can be achieved through a process of annealing, acetone and HCl purification followed by either H2O2 and HClO4 or Br2 treatment.

High levels of soluble vascular endothelial growth factor receptor 1/sFlt1 and low levels of vascular endothelial growth factor in follicular fluid on the day of oocyte retrieval correlate with ovarian hyperstimulation syndrom regardless of the stimulation protocol.

The aim of the study was to assess the predictive value of vascular endothelial growth factor (VEGF), its soluble receptor - sVEGF-R1/sFlt1 and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) concentrations in serum and follicular fluid (FF) for ovarian hyperstimulation syndrome (OHSS) in women undergoing controlled ovarian hyperstimulation (COH) protocols. Patients have been divided into 3 groups: control group on natural cycle, patients stimulated with GnRH agonist and patients stimulated with GnRH antagonist. The FF and serum concentrations of VEGF, EG-VEGF, sVEGF R1 and the expression of VEGF and EG-VEGF mRNA in GC in small and large follicles collected from patients were investigated. When we compared all patients in a trial, OHSS occurrence was correlated with higher level of sVEGF R1 and a lower level of VEGF in a follicular fluid from large follicles in a day of oocyte retrieval. The VEGF/sVEGF-R1 ratio for patients in COH groups, above which the risk of developing OHSS is very low (OR 0.1 (95% CI 0.01 - 0.29, P = 0.0006) was found to be 0.281 pg/ml, with AUC - 0.738, P = 0.042, (95% CI 0.656 - 0.82). High levels of sVEGF-R1 and low level of VEGF in FF on the day of oocyte retrieval correlate with OHSS regardless of the stimulation protocol.

The role of carbon precursor on carbon nanotube chirality in floating catalyst chemical vapour deposition.

We have studied the influence of different carbon precursors (methane, ethanol and toluene) on the type, diameter and chiral angle distributions of carbon nanotubes (CNTs) grown with the floating catalyst technique in a horizontal gas-flow reactor. Using electron diffraction to study their atomic structures, we found that ethanol and toluene precursors gave high single-wall CNT yields (92% and 89% respectively), with narrow diameter distributions: 1.1 nm to 1.7 nm (ethanol); 1.3 nm to 2.1 nm (toluene), with a propensity for armchair-type chiral angles. In contrast, methane-grown CNTs gave high double-wall CNT yields (75%) with broader diameter populations: 1.2 to 4.6 nm (inner CNT) and 2.2 to 5.3 nm (outer CNT) with a more uniform spread of chiral angles, but weakly peaked around 15 to 20 degrees. These observations agree with known growth models. However, double-wall CNTs grown with toluene showed an unusually narrow interlayer spacing of 0.286 ± 0.003 nm with suggestions of large, 20° to 25°, differences between inner and outer CNT chiral angles. Methane gave a large interlayer spacing (0.385 ± 0.002 nm) with suggestions of small 5° to 10° inter-tube chirality correlations.

Changes in gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor gene expression after an increase in carbon monoxide concentration in the cavernous sinus of male wild boar and pig crossbread.

Previous studies indicate that there are at least a few regulatory systems involved in photoperiodic synchronisation of reproductive activity, which starts with the retina and ends at the gonadotropin-releasing hormone (GnRH) pulse generator. Recently we have shown indicated that the amount of carbon monoxide (CO) released from the eye into the ophthalmic venous blood depends on the intensity of sunlight. The aim of this study was to test whether changes in the concentration of carbon monoxide in the ophthalmic venous blood may modulate reproductive activity, as measured by changes in GnRH and GnRH receptor gene expression. The animal model used was mature male swine crossbred from wild boars and domestic sows (n = 48). We conducted in vivo experiments to determine the effect of increased CO concentrations in the cavernous sinus of the mammalian perihypophyseal vascular complex on gene expression of GnRH and GnRH receptors as well as serum luteinizing hormone (LH) levels. The experiments were performed during long photoperiod days near the summer solstice (second half of June) and short photoperiod days near the winter solstice (second half of December). These crossbred swine demonstrated a seasonally-dependent marked variation in GnRH and GnRH receptor gene expression and systemic LH levels in response to changes in CO concentration in ophthalmic venous blood. These results seem to confirm the hypothesis of humoral phototransduction as a mechanism for some of bright light's effects in animal chronobiology and the effect of CO on GnRH and GnRH receptor gene expression.

Polystyrene grafted multi-walled carbon nanotubes.

Oxidised, multi-walled, carbon nanotubes can be grafted with polystyrene molecules using an situ radical polymerisation reaction, thereby dramatically modifying their solubility and their suitability for nanocomposite applications.

Modified antibiotics-methylated ampicillin and ethylated ampicillin-inhibit growth of ampicillin-resistant strain of bacteria.

Bacterial resistance to antibiotics is a significant problem in health facilities and results in higher costs for health care and increased fatalities due to infection. The work presented here suggests that antibiotic molecular structure can be altered in a selected manner, which will revive the bacterial growth inhibiting capability. A bacterial strain PKK3535(DH1), which is resistant to the antibiotic ampicillin, was found to be highly growth inhibited by these altered forms of ampicillin when tested in tissue culture. The level of growth inhibition of bacterial strain PKK3535(DHI) was greater than 50%, for both molecular variants of ampicillin that were investigated. The bacteria strain used for testing was a clinical isolate obtained from the University Hospital of the University of Nebraska, Omaha. These two antibiotic variants were methylated ampicillin and ethylated ampicillin. The synthetic procedure for generating these variants is presented as well as the molecular structure. The methylated and ethylated ampicillin were found to be stable at 0 degrees C for many weeks, were somewhat less soluble than normal ampicillin, but dissolved in LB plate media. The resistant bacteria strain was plated onto LB media with altered ampicillin and profound inhibition of bacteria growth was seen within the first 24 hours of incubation. These molecular variants of ampicillin provide evidence of a means to combat the proliferation of resistant bacterial strains. The molecular alteration of antibiotics may provide a suitable means to study and combat the appearance of antibiotic-resistant bacteria.

[Percutaneous sperm retrieval for ICSI procedures in men with obstructive azoospermia: ICSI-PESA and ICSI-TESE micromanipulation: our experience]. / Wlasne doswiadczenia w przezskórnym pozyskiwaniu plemników do zaplodnienia pozaustrojowego ICSI-PESA oraz ICSI-TESE u mezczyzn z azoospermia obstrukcyjna.

OBJECTIVES: The sperm retrieval for ICSI procedures is possibly using following procedures: ejaculate sperm, epididymal sperm obtained by microsurgical aspiration or percutaneous puncture and testicular sperm that are obtained by surgical excision or percutaneous biopsy. Percutaneous techniques seem to be rather simple and effective procedures. DESIGN: The authors present their own experiences with percutaneous sperm retrieval for micromanipulation ICSI from the epididymis (ICSI-PESA) and from the testicular tissue (ICSI-TESE) in men with obstructive azoospermia and with reactive impotence. First time in Poland ICSI-PESA was done on April 11, 1996 in Private Infertility Center "Novum", Warsaw. MATERIAL AND METHODS: From April 1996 to the end of January 1998, 10 ICSI-PESA procedures (in 9 couples) and 8 ICSI-TESE (in 6 couples) were performed. In one case ICSI-PESA was performed in man with psychological inability of masturbation during his wife's IVF protocol. All procedures were performed as the day case urology, under general anesthesia. The fine needles No 6 in PESA or biopsy needle from Hepafix Set B. Braun in TESE were used. The therapy of antibiotic and common analgesic drug was used routinely after puncture. RESULTS: The effectiveness of obtaining sperm for micromanipulation were 100% ICSI-PESA and 75% ICSI-TESE. The pregnancy rate in PESA was 50% and 5 healthy children were born. In TESE only 1 woman (17%) was pregnant, but early spontaneous miscarriage was reported. No surgical and anesthesiological complications were noticed. CONCLUSIONS: Obtaining sperm for micromanipulation ICSI using percutaneous epididymal puncture or testicular tissue needle biopsy seems to be effective and safe for patients with obstructive azoospermia or reactive impotence.

[Needle testicular biopsy in the diagnosis of male infertility]. / Iglowa biopsja jader w diagnostyce nieplodnosci meskiej.

OBJECTIVES: Evaluation of testicular tissue is very important diagnostic procedures in cryptozoospermia and azoospermia. It is verified the patient for treatment (stimulation spermatogenesis), for micromanipulation ICSI or for insemination donor semen procedure. Surgical biopsy is very popular between andrologist and urologist, but needle biopsy seems to be easier and safer. DESIGN: The authors present their experience with needle testicular biopsy during the diagnosis patients with azoospermia or cryptozoospermia and the men with paraplegia after trauma and without ejaculation. MATERIAL AND METHODS: The study group included 63 biopsies in 58 men with azoospermia and severe oligoasthenozoospermia (cryptozoospermia) and 2 with paraplegia. The specimens were taken from 125 testes under general anesthesia (i.v-Diprivan, Propofol, Zeneca and Fentanyl) using biopsy needle from Hepafix B. Braun Melsungen, Germany. All procedures were performed as a day case. RESULTS: In 95% specimens were adequate for histopathological investigations and for planning the treatment. Only one complication (0, 8%) -small haematoma testis was observed. CONCLUSIONS: The needle biopsy of testicular tissue is sufficiency in histopathological examination, safe for patients and easy for urologists. The total cost is much more lower than cost of surgical biopsy.

A review of production methods of carbon nanotube and graphene thin films for electrothermal applications.

Electrothermal materials transform electric energy into heat due to the Joule effect. To date, resistive wires made of heavy metal alloys have primarily been used as the heat source in many appliances surrounding us. Recent discoveries in the field of carbon nanostructures revealed that they can offer a spectrum of advantages over the traditional materials. We review the production methods of thin films composed of carbon nanotubes or graphene and depict how they can be used as conductive coatings for electrothermal applications. We screen all reports from the field up to now and highlight the features of designed nanoheaters. A particular focus is placed on the analysis of general findings of how to tune their electrothermal properties, why carbon nanostructure devices operate the way they do and in what aspects they are superior to the currently available materials on the market.

Colonic volvulus as a complication of celiac sprue.

Colonic volvulus has been a rarely reported complication of celiac sprue. We describe two patients with long-standing celiac sprue, one in whom a recurrent sigmoid volvulus developed, and in the other, a cecal volvulus. Following surgery, both are now asymptomatic on a gluten-free diet. The association between celiac sprue and colonic volvulus was first reported in 1953. There have been only a few isolated cases documented, surprisingly so because the two major predisposing conditions for colonic volvulus are often seen in patients with celiac sprue. Colonic bacterial fermentation of malabsorbed carbohydrate (in celiac sprue) leads to excess gas production. Flaccid bowel loops with sigmoid redundancy, a long mesentery, or cecal hypermobility are not uncommon. A motility disorder in celiac sprue has also been proposed. Thus these factors together would suggest that the likelihood of development of colonic volvulus in celiac sprue would be relatively great. The possibility of underlying celiac sprue should be considered in patients with colonic volvulus who have a background history of recurrent abdominal distention or malabsorptive symptoms.

Synthesis and analysis of ethylated tetracycline, an antibiotic derivative that inhibits the growth of tetracycline-resistant XL1-Blue bacteria.

Bacterial resistance to antibiotics is a significant problem in medical care facilities, causing increased fatalities due to infection. The present study demonstrates that antibiotic structures can be selectively altered in a manner that revives their ability to inhibit bacterial growth. The antibiotic tetracycline was ethylated at the position of the phenolic hydroxy group with the use of diazoethane, forming an ethyl ether functional group. This derivative was dissolved in Luria-Bertani (LB) agar medium, then placed in tissue culture for screening against a tetracycline-resistant bacterial strain. The growth of this bacterial strain, designated XL1-Blue, was inhibited by the ethylated form of tetracycline. The procedure for synthesizing ethylated tetracycline utilizes diazoethane and is presented with the molecular structures and IR spectra. The ethylated form of tetracycline was stable at -20 degrees C for many weeks, and was soluble in LB agar plate medium. Ethylated tetracycline induced growth inhibition of XL1-Blue bacteria within the first 24 h of incubation. The level of bacterial growth inhibition was greater than 30%. Calculation of the partition coefficient, log P, was accomplished and indicates that ethylated tetracycline has an increased lipophilic tendency relative to unmodified tetracycline, and therefore has greater solubility in lipid bilayers.

Medicaid utilization of services in a prepaid group practice health plan.

To provide medical service at lower costs without diminishing either quality or coverage, the District of Columbia enrolled approximately 1,000 Medicaid beneficiaries, voluntarily, in a prepaid group practice (PGP). The project was evaluated over a three-year period (1971-1974) with regard to: 1) rate of utilzation of medical care before and after enrollment; 2) costs of care per capita as compared with those of the 160,000 beneficiaries in the Medicaid fee-for-service universe; and 3) patient satisfaction with the PGP. Results indicate that for the 834 individuals aged 1 through 64 enrolled in the PGP; ambulatory physican encounter rates decreased 15 per cent, drug utilization was down 18 per cent, hospital admissions decreased 30 per cent, and hospital days declined 32 per cent after enrollment. For the same benefit package, annual prepaid per capita costs for the Medicaid PGP enrollees for 1972, 1973, 1974 were only +282, +232, and +286 respectively, representing a 37 per cent saving when compared to the fee-for-service per capita costs of the Medicaid Universe which stood of +373, +435 and +465 over the same period. The instrument used to probe patient satisfaction showed the Study Group was satisfied with the PGP, and received better dental care. The voluntary dropout rate from the PGP was only 2.5 per cent; and out-of-plan utilization was low, indicating good acceptance of the PGP service.