Metabolism of the Synthetic Cathinone Alpha-Pyrrolidinoisohexanophenone in Humans Using UHPLC--MS-QToF.

Alpha-pyrrolidinoisohexanophenone (α-PHiP/α-PiHP) is a synthetic drug structurally related to cathine, a natural psychoactive alkaloid, isolated from Khat plant. The α-PiHP is a structural isomer of α-PHP, and both α-PHP and α-PiHP could be considered an analog of α-PVP, a Schedule I drug under the Convention on Psychotropic Substances by the United Nations. This α-pyrrolidinophenone was first reported to European Monitoring of Drug and Drug Addiction by Slovenia in December 2016. In Hungary, it was initially reported in August 2016, and until 2021, it had been detected in seizures only twice and never been identified in biological samples. However, in 2021, its consumption became prevalent in Hungary. This study aims to investigate the α-PiHP metabolites by performing in vitro and in vivo metabolite identification studies of human liver microsome (pHLM), S9 fraction (pS9) and urine samples (from control and users), using liquid chromatography in conjunction with high-resolution mass spectrometry. Ten in vivo urinary metabolites of α-PiHP were tentatively identified and confirmed by in vitro metabolites detected in pHLM and pS9 samples. Among the eight Phase I and the two Phase II metabolites, five were more abundant in urine than the parent compound. The two major metabolites via reduction of the keto moiety (M01) and via oxidation of the pyrrolidine ring combined with aliphatic hydroxylation and keto reduction (M06) were identified. The metabolites via the combination of keto reduction and aliphatic hydroxylation (M04), via ring-opening followed by carboxylation (M09) and via glucuronidation of the keto reduced metabolite (M07) were also dominant. The minor metabolites were one Phase II metabolite (M08), two metabolites via aliphatic hydroxylation (M02 and M03), one metabolite via the combination of keto reduction and oxidation of the pyrrolidine ring (M05) and one metabolite via oxidation of the pyrrolidine ring (M10).

BAHA Attract to Osia conversion patients: comparison of the two systems and long-term outcomes.

OBJECTIVE: Osia is a new, transcutaneous, active bone-conduction implant. This study aimed to compare the BAHA Attract and the first-generation Osia system after BAHA Attract to Osia conversion surgery. METHOD: Five patients who had previously used the BAHA Attract system were converted to the first generation of the Osia system. Surgical aspects of the two different systems, audiological performance and subjective opinions of the patients were investigated. Pure tone audiometry and speech audiometry in quiet was performed with each patient's BAHA 5 sound processor on Attract, and the test battery was repeated six weeks after the Attract to Osia conversion and at different time points after the first fitting. Details of the surgery and patients' feedback were analysed. RESULTS: Audiology tests showed significant improvement when using either system; however, the Osia system performance was better. Based on patient feedback, all the five implantees preferred the Osia system. CONCLUSION: The study results suggest that the Osia system is a safe and powerful hearing implant that provides good clinical outcomes.

Puccinia graminis f. sp. tritici Population Causing Recent Wheat Stem Rust Epidemics in Kazakhstan Is Highly Diverse and Includes Novel Virulence Pathotypes.

Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is a reemerging disease that caused severe epidemics in northern Kazakhstan and western Siberia in the period of 2015 to 2019. We analyzed 51 stem rust samples collected between 2015 and 2017 in five provinces in Kazakhstan. A total of 112 Pgt races were identified from 208 single-pustule isolates. These races are phenotypically and genotypically diverse, and most of them are likely of sexual origin. No differentiation of phenotypes and single-nucleotide polymorphism genotypes was observed between isolates from Akmola and North Kazakhstan provinces, supporting the idea of a wide dispersal of inoculum in the northern regions of the country. Similarities in virulence profiles with Pgt races previously reported in Siberia, Russia, suggest that northern Kazakhstan and western Siberia constitute a single stem rust epidemiological region. In addition to the races of sexual origin, six races reported in Europe, the Caucasus, and East Africa were detected in Kazakhstan, indicating that this epidemiological region is not isolated, and spore inflow from the west occurs. Virulence alone or in combination to several genes effective against the Ug99 race group was detected, including novel virulence on Sr32 + Sr40 and Sr47. The occurrence of a highly diverse Pgt population with virulence to an important group of Sr genes demonstrated the importance of the pathogen's sexual cycle in generating new and potentially damaging virulence combinations.

Primary alterations during the development of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland-rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin. OBJECTIVES: We aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non-lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein-based methods. METHODS: Immune cell counts (T cells, dendritic cells, macrophages), Th1/Th17-related molecules (IL-12B, TBX21, IFNG, TNFA, IL-17, IL10, IL-23A, TGFB1, RORC, CCL20), keratinocyte-related sensors (TLR2,4), mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP, CCL2) and pro-inflammatory molecules (IL1B, IL6, TNFA, IL-23A) were investigated in the three groups by RNASeq, RT-qPCR, immunohistochemistry and immunofluorescence. RESULTS: Epidermal changes were already detectable in non-lesional HS skin; the epidermal occurrence of antimicrobial peptides (AMPs), IL-1ß, TNF-α and IL-23 was highly upregulated compared with healthy AGR skin. In lesional HS epidermis, TNF-α and IL-1ß expression remained at high levels while AMPs and IL-23 increased even more compared with non-lesional skin. In the dermis of non-lesional HS skin, signs of inflammation were barely detectable (vs. AGR), while in the lesional dermis, the number of inflammatory cells and Th1/Th17-related mediators were significantly elevated. CONCLUSIONS: Our findings that non-lesional HS epidermal keratinocytes produce not only AMPs and IL-1ß but also high levels of TNF-α and IL-23 confirm the driver role of keratinocytes in HS pathogenesis and highlight the possible role of keratinocytes in the transformation of non-inflammatory Th17 cells (of healthy AGR skin) into inflammatory cells (of HS) via the production of these mediators. The fact that epidermal TNF-α and IL-23 appear also in non-lesional HS seems to prove these cytokines as excellent therapeutic targets.

Space use of wild boar (Sus Scrofa) in Budapest: are they resident or transient city dwellers?

In our study, we examined the movement of two wild boars marked with GPS/GSM transmitters in city of Budapest. We hypothesised that: the wild boars do not leave the urban area (H1); the wild boars prefer places that are less disturbed by people, and which are rich in potential hiding places (H2); and their home ranges would be smaller than that of wild boars living in non-urban environment (H3). Based on our results, we accepted our first hypothesis, as the wild boars had not left the area of Budapest. However, we partly rejected our second hypothesis: the wild boars preferred urban areas that were forested and richly covered with vegetation; however, human presence therefore disturbance was also high in those areas. The home range sizes of both marked wild boar sows were remarkably smaller than those of the wild boars living in natural environment (H3). City habitat modification, e.g. clearing undergrowth vegetation, could result that wild boars cannot find any hiding places. The significant part of food sources will disappear with the elimination of these places. By eliminating the two main factors together could prevent wild boars finding their living conditions within the city.

Older Donation After Circulatory Death Kidneys for Older Recipients: A Single-Center Experience.

The number of older patients is increasing on the transplant waiting list. Donation after circulatory death (DCD) kidney transplantation has increased, but there remains hesitancy in use of older DCD organs. The aim of this study was to evaluate outcomes of directing older DCD donor kidneys into older recipients. METHODS: Patients 60 years or older who received transplants from DCD donors 60 years or older, between February 2010 and January 2014, were identified from a prospectively maintained database. RESULTS: Over a 4-year period, 88 patients 60 years or older received DCD kidney transplants from donors 60 years or older. Of these 44 (55%) were 60 to 69 years old and 40 (45%) were 70 years or older. Median follow up was 63 months. Patient survival was 95% and 79% at 1 and 5 years, respectively, with a survival in those 70 years and older (69%) compared with those aged 60 to 69 (88%) years (P = .01). Censored for death graft survival was 94% and 80% at 1 and 5 years, respectively. Median estimated glomerular filtration rate at 12 months and 36 months was 36 mL/min (range, 11-70 mL/min) and 39.5 mL/min (range, 11-77 mL/min), respectively. CONCLUSIONS: Older DCD kidneys, when transplanted into older recipients, result in good patient and graft survival and an acceptable graft function, especially considering their age. This represents a good use of this organ resource.

Influence of ionizing radiation on the antimicrobial activity of the antibiotics sulfamethoxazole and trimethoprim.

The response of the antimicrobial compounds sulfamethoxazole (SMX) and trimethoprim (TMP) - individually and in mixtures - to ionizing radiation was investigated using laboratory prepared mixtures and a commercial pharmaceutical formulation. The residual antibacterial activity of the solutions was monitored using Staphylococcus aureus and Escherichia coli test strains. Based on antibacterial activity, SMX was more susceptible to ionizing radiation as compared to TMP. The antibacterial activity of SMX and TMP was completely eliminated at 0.2 kGy and 0.8 kGy, respectively. However, when SMX and TMP were in a mixture, the dose required to eliminate the antibacterial activity was 10 kGy, implying a synergistic antibacterial activity when these are present in mixtures. Only when the antibiotic concentration was below the Minimum Inhibitory Concentration of TMP (i.e., 2 µmol dm-3) did the antibacterial activity of the SMX and TMP mixture disappear. These results imply that the synergistic antimicrobial activity of antimicrobial compounds in pharmaceutical waste streams is a strong possibility. Therefore, antimicrobial activity assays should be included when evaluating the use of ionizing radiation technology for the remediation of pharmaceutical or municipal waste streams.

Dual Kidney Transplantation Offers a Valuable Source for Kidneys With Good Functional Outcome.

BACKGROUND: Reasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome. METHODS: Patients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age. RESULTS: Over a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5-79) and 42 (range, 15-85) mL/min compared with SKT of 35 (range, 10-65) and 32 (range, 6-65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% (P = .52), and patient survival was 94% and 98%, respectively (P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group. CONCLUSIONS: Graft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission.

[Shock in infants and children]. / Schock im Kindesalter.

The clinical signs and symptoms of shock in newborns and children are often more subtle compared to adults. Recurring, avoidable factors for optimal outcome include failure of health care workers to recognize shock at the time of presentation. Children are able to compensate a shock state for longer periods than adults resulting in a sudden, sometimes irreversible, cardiopulmonary collapse. Different forms of shock, their therapy, and frequent errors are depicted and illustrated with practical examples. Early recognition of shock in children is crucial for optimal outcome but is not always obvious. Clinical experience, gut feeling, and careful and repeated interpretation of the vital parameters are essential to recognize and effectively treat the various forms of shock.

Identification of the WNT1 residues required for palmitoylation by Porcupine.

The post-translational palmitoylation of WNT morphogens is critical for proper signaling during embryogenesis and adult homeostasis. The addition of palmitoyl groups to WNT proteins is catalyzed by Porcupine (PORCN). However, the Wnt amino acid residues required for recognition and palmitoylation by PORCN have not been fully characterized. We show that WNT1 residues 214-234 are sufficient for PORCN-dependent palmitoylation of Ser224. Substitution of Ser224 with Thr, but not Cys, is tolerated in palmitoylation and biological assays. Our data highlight the importance of palmitoylation for WNT1 activity and establish PORCN as an O-acyl transferase for WNT1.

Three-year longitudinal clinical trial of arterial function assessed by a oscillometric non-invasive method in comparison with carotid sclerosis and transferrin kidney-transplanted patients.

Chronic kidney disease remains one of the main risk factors of cardiovascular disease. However, patients with kidney transplantation have better life expectancy and better quality of life compared with patients on dialysis. In patients with a well-functioning graft, the main cause of death is cardiovascular in origin. Metabolic pathways have complex effects on arterial function that can be monitored by conventional ultrasonography and with the assessment of arterial stiffness by oscillometric non-invasive technique. Forty-one primer cadaver kidney-transplanted patient were involved in a 3-year longitudinal clinical trial (21 female, 20 male; average age, 40.16 ± 12.56 years). Arterial stiffness parameters referring to rigidity of the arterial wall (pulse wave velocity [PWV], augmentation index, and pulse pressure) were investigated. Correlation between stiffness, and laboratory parameters (serum creatinine, urea, hemoglobin, albumin, cholesterine, triglycerides, transferrin, uric acid, glomerular filtration rate, and C-reactive protein) were analyzed. A non-invasive oscillometric method--Tensiomed Arteriograph--was applied to assess the arterial stiffness parameters. Statistical analysis was performed with the use of Statistica for Windows, version 8.0. A value of P < .05 was considered statistically significant for all statistical tests. We found a positive correlation between PWV and left ventricular wall thickness and a negative correlation between PWV and ejection fraction. We also found a positive significant correlation between serum level of transferrin and PWV. There was simultaneous significant progression concerning PWV and carotid artery sclerosis in a 3-year follow-up. There was no fatal cardiovascular event during the study period among our patients. All of our patients involved in this study are still alive. Our findings suggest that arterial stiffness monitoring is a reliable method to assess global cardiovascular risk among kidney-transplanted patients. The oscillometric method is convenient, fast, painless technique to monitor arterial function, which, in the case of pathological findings, proposes more frequent cardiovascular control.

Noninvasive perioperative monitoring of arterial function in patients with kidney transplantation.

Development of atherosclerosis is accelerated in kidney transplant recipients. Impaired metabolic pathways have a complex effect on the arterial wall, which can be measured by noninvasive techniques. Few data are available on the change of stiffness parameters in the postoperative course, so in this study we analyzed the stiffness parameters of kidney transplant recipients during the perioperative period. Seventeen successful primary kidney transplant patients with uneventful postoperative period (7 woman, 10 men; 46.16 ± 12.19 years) were involved in our short-term prospective longitudinal study. We analyzed the correlation between noninvasively assessed stiffness parameters (pulse wave velocity [PWV], augmentation index [AIx], pulse pressure [PP], systolic area index, diastolic area index, diastolic reflection area), ankle-brachial index (ABI), and laboratory parameters (creatinine, glomerular filtration rate, urea, haemoglobin, C-reactive protein). Stiffness parameters were measured with a Tensiomed Arteriograph. These parameters were assessed before the transplantation, and 24 hours, and 1 and 2 weeks after surgery under standard conditions. We found that creatinine (P = .0008) and C-reactive protein (P = .006) serum levels decreased, and glomerular filtration rate increased significantly (P = .0005). We revealed that PWV (P = .0075) and AIx (P = .013) improved significantly. There was no significant change in ABI, PP, and the other monitored parameters. Along with the available data in the literature, our findings suggest that kidney transplantation has a positive effect on the arterial function.

Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) often occurs following pancreatic surgery. AIM: To demonstrate the superior efficacy of pancreatin 25 000 minimicrospheres (Creon 25000 MMS; 9-15 capsules/day) over placebo in treating PEI after pancreatic resection. METHODS: A 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study with a 1-year, open-label extension (OLE). Subjects ≥18 years old with PEI after pancreatic resection, defined as baseline coefficient of fat absorption (CFA) <80%, were randomised to oral pancreatin or placebo (9-15 capsules/day: 3 with main meals, 2 with snacks). In the OLE, all subjects received pancreatin. The primary efficacy measure was least squares mean CFA change from baseline to end of double-blind treatment (ancova). RESULTS: All 58 subjects randomised (32 pancreatin, 26 placebo) completed double-blind treatment and entered the OLE; 51 completed the OLE. The least squares mean CFA change in the double-blind phase was significantly greater with pancreatin vs. placebo: 21.4% (95% CI: 13.7, 29.2) vs. -4.2% (-12.8, 4.5); difference 25.6% (13.9, 37.3), P < 0.001. The mean ± s.d. CFA increased from 53.6 ± 20.6% at baseline to 78.4 ± 20.7% at OLE end (P < 0.001). Treatment-emergent adverse events occurred in 37.5% subjects on pancreatin and 26.9% on placebo during double-blind treatment, with flatulence being the most common (pancreatin 12.5%, placebo 7.7%). Only two subjects discontinued due to treatment-emergent adverse events, both during the OLE. CONCLUSIONS: This study demonstrates superior efficacy of pancreatin 25 000 over placebo in patients with PEI after pancreatic surgery, measured by change in CFA. Pancreatin was generally well tolerated at the high dose administered (EudraCT registration number: 2005-004854-29).

Lytic and mechanical stability of clots composed of fibrin and blood vessel wall components.

BACKGROUND: Proteases expressed in atherosclerotic plaque lesions generate collagen fragments, release glycosaminoglycans (chondroitin sulfate [CS] and dermatan sulfate [DS]) and expose extracellular matrix (ECM) proteins (e.g. decorin) at sites of fibrin formation. OBJECTIVE: Here we address the effect of these vessel wall components on the lysis of fibrin by the tissue plasminogen activator (tPA)/plasminogen system and on the mechanical stability of clots. METHODS AND RESULTS: MMP-8-digested collagen fragments, isolated CS, DS, glycosylated decorin and its core protein were used to prepare mixed matrices with fibrin (additives present at a 50-fold lower mass concentration than fibrinogen). Scanning electron microscopy (SEM) showed that the presence of ECM components resulted in a coarse fibrin structure, most pronounced for glycosylated decorin causing an increase in the median fiber diameter from 85 to 187 nm. Rheological measurements indicated that these structural alterations were coupled to decreased shear resistance (1.8-fold lower shear stress needed for gel/fluid transition of the clots containing glycosylated decorin) and rigidity (reduction of the storage modulus from 54.3 to 33.2 Pa). The lytic susceptibility of the modified fibrin structures was increased. The time to 50% lysis by plasmin was reduced approximately 2-fold for all investigated ECM components (apart from the core protein of decorin which produced a moderate reduction of the lysis time by 25%), whereas fibrin-dependent plasminogen activation by tPA was inhibited by up to 30%. CONCLUSION: ECM components compromise the chemical and mechanical stability of fibrin as a result of changes in its ultrastructure.

First Report of Garlic Rust Caused by Puccinia allii on Allium sativum in Minnesota.

High-quality garlic is an emerging crop grown in Minnesota for local markets, community supported agriculture, and select restaurants. In July 2010, Allium sativum cv. German Extra Hardy Porcelain plants showing foliar symptoms typical of rust infection were brought to the Plant Disease Clinic at the University of Minnesota by a commercial grower from Fillmore County, Minnesota. Infected leaves showed circular to oblong lesions (1 to 3 mm long), which ranged in color from yellow-orange (uredinia) to black (telia). Urediniospores collected from uredinia were globoid to ellipsoid, yellowish in color, and measured 18 ± 1 × 30 ± 2 µm with a wall thickness of 2.4 ± 0.5 µm. Teliospores were two celled, 18 ± 3 × 47 ± 10 µm, with a projected cross-sectional area (1) of 826 ± 87 µm2; cell walls were smooth, brown, 1.6 ± 0.3 µm (proximal cell) to 2.1 ± 0.5 µm (distal cell) thick, and 4.2 ± 0.8 µm at the apex. The pathogen was identified as Puccinia allii (2) and a sample was deposited in the U.S. National Fungus Collection (BPI 884132). DNA was extracted from infected leaf tissue and the nuclear ribosomal internal transcribed spacer region (ITS) and 5' end of the large subunit (LS) was amplified and sequenced as described by Anikster et al. (1). The 1,257-bp sequence from the sample collected in Minnesota (GenBank Accession No. JX402206) was identical to ITS/LS sequence of a sample of P. allii collected from garlic in California (GenBank Accession No. AF511077), with the exception that MN sequence contained nine "A"s rather than 10 in the hyper-variable area at the 3' end of the ITS region. P. allii has been shown to be a species complex comprising at least two different types, "leek type" and "garlic type" (1). Based on the ITS sequence and the projected cross-sectional area of the teliospores, the sample of P. allii from MN is consistent with the garlic type. Garlic rust occurred in localized foci late in the growing season and therefore did not cause significant loss to the 2010 crop. Reoccurrence of garlic rust was not reported in either 2011 or 2012 growing seasons in Minnesota. P. allii all but eliminated commercial garlic production in California in the late 1990s (1) and has the potential to cause significant negative impact to the emerging garlic crop in Minnesota. However, the epidemiology of garlic rust in the northern U.S. is not well understood and therefore predicting the risk of the Minnesota garlic crop to rust is difficult. References: (1) Y. Anikster et al. Phytopathology 94:569, 2004. (2) L. J. Szabo et al, Rust. Pages 41-44 in: Compendium of Onion and Garlic Diseases and Pests, Second Edition. H. F. Schwartz and S. K. Mohan, eds. APS Press, St. Paul, 2008.

First Report of Puccinia veronicae-longifoliae on Veronica spicata 'Royal Candles' in Minnesota.

In September 2008, Veronica spicata 'Royal Candles' plants showing foliar symptoms typical of a rust infection were brought to the Plant Disease Clinic at the University of Minnesota. Plants were grown in a local nursery in Dakota County, Minnesota. A dark brown discoloration was apparent on the upper surface of the leaf with lighter brown pustules on the underside. Teliospores collected from the pustules were 2-celled with smooth walls and 36.35 to 48.87 µm long, 11.96 to 18.28 µm wide, and had a wall thickness of 1.33 to 2.61 µm, which is in accordance with type specimen of Puccinia veronicae-longifoliae (4). Pathogen identity was confirmed by comparison of the DNA sequence of nuclear ribosomal RNA region containing the internal transcribed spacer regions 1 and 2, 5.8S and the 5' end of the 28S subunits between herbarium samples from the U.S. National Fungus Collection (BPI 841971/GenBank Accession JQ627617 and BPI 871789/GenBank Accession JQ627618) and the collected specimen (BPI 882886/GenBank Accession JQ627616). P. veronicae-longifoliae was first reported in the United States in 2004 from a commercial nursery in Michigan (2). Veronica rust has also been found in Michigan in 2005 and more recently in 2011 (1). The only other known report of Veronica rust in the United States occurred in Connecticut in 2007 (3). P. veronicae-longifoliae is not considered a quarantine pest by The Animal and Plant Health Inspection Service due to the limited host range, the host not being on the threatened or endangered list and the host being of little economic or environmental importance (2). References: (1) T. A. Dudek et al. MSU Extension News. Retrieved from http://msue.anr.msu.edu/news/veronica_rust_observed_this_season/ , 2011. (2) North American Plant Protection Organization's Phytosanitary Alert System. Retrieved from http://www.pestalert.org/oprDetail.cfm?oprID=129 , 2004. (3) Pundt, L. Floriculture Greenhouse Update. Retrieved from http://www.negreenhouseupdate.info/index.php/july/194-rust-on-veronica , 2007. (4) D. B. O. Savile. Can. J. Bot. 46:631, 1968.

Retinal and renal vascular permeability changes caused by stem cell stimulation in alloxan-induced diabetic rats, measured by extravasation of fluorescein.

AIM: To determine whether treatment with the stem cell stimulator Olimpiq® Stem×Cell prevents increase of retinal and renal vascular permeability in alloxan-induced diabetic rats. MATERIALS AND METHODS: Two groups of Wistar rats were made diabetic by single intraperitoneal injection of Alloxan. The third, the control group, received vehicle alone. One diabetic group received Olimpiq® Stem×Cell treatment for 4 weeks. The permeability of the blood-retinal barrier (BRB) and renal vessels were measured by the extravasation of fluorescein-labeled bovine serum albumin. RESULTS: Six weeks subsequently to Alloxan injection, significantly elevated the tissue fluorescence, the renal vascular leakage and BRB breakdown was demonstrated in the diabetic group, compared to the nondiabetic group. Olimpiq® Stem×Cell treatment significantly reduced the BRB breakdown, tissue fluorescence, and vascular leakage. CONCLUSION: Olimpiq® Stem×Cell would be a useful choice of treatment for complications associated with increased vascular permeability of diabetes, such as retinopathy or nephropathy.

Mutational spectrum of smith-lemli-opitz syndrome patients in hungary.

Smith-Lemli-Opitz (SLO) syndrome is an autosomal recessive disorder characterized by multiple congenital abnormalities and mental retardation. The condition is caused by the deficiency of 7-dehydrocholesterol reductase (DHCR7) which catalyzes the final step in cholesterol biosynthesis. Biochemical diagnosis is based on increased concentration of 7-dehydrocholesterol (7-DHC) in the patient serum. Both life expectancy and quality of life are severely affected by the disease. The estimated prevalence of SLO syndrome ranges between 1:20,000 and 1:40,000 among Caucasians. Although the mutational spectrum of the disease is wide, approximately 10 mutations are responsible for more than 80% of the cases. These mutations show a large interethnic variability. There are no mutation distribution data from Hungary to date. Thirteen patients were diagnosed with SLO syndrome in our laboratory. As first-line tests, serum 7-DHC and total cholesterol were measured and, in positive cases, molecular genetic analysis of the DHCR7 gene was performed. Complete genetic background of the disease could be identified in 12 cases. In 1 case only 1 mutation was detected in a heterozygote form. One patient was homozygous for the common splice site mutation c.964-1G>C, while all other patients were compound heterozygotes. One novel missense mutation, c.374A>G (p.Tyr125Cys) was identified.

First Report of a New TTKSF Race of Wheat Stem Rust (Puccinia graminis f. sp. tritici) in South Africa and Zimbabwe.

Seven races have been described in the Ug99 race group of Puccinia graminis f. sp. tritici (2). Ug99-related races previously recorded in South Africa are TTKSF, TTKSP, and PTKST (4). In December 2010, severe stem rust infection of the winter wheat cv. Matlabas was observed for the first time in South Africa. Race analysis using the 20 North American (NA) stem rust differential lines and letter code system classified the race as TTKSF. In comparative infection studies in a greenhouse, cv. Matlabas seedlings were susceptible (infection type [IT] 4) to isolate UVPgt61/1 (TTKSF+) collected from Afrikaskop in the eastern Free State, whereas the cultivar was resistant (IT 1 to 2) to stem rust isolates 2013 (TTKSF), UVPgt55 (TTKSF), UVPgt59 (TTKSP), and UVPgt60 (PTKST). Isolate 2013 represents the original collection of race TTKSF in South Africa (1). In addition to the NA differentials, no variation in the IT range of seedlings of lines with Sr7a, 8b, 12, 13, 14, 16, 18, 19, 22, 25, 26, 27, 28, 29, 32, 33, 34, 35, 39, 41, 42, 43, 44, Em, R, Tt2, and Satu was observed between UVPgt61/1 and UVPgt55. With the exception of cv. Matlabas, ITs of 106 South African cultivars likewise did not differentiate UVPgt61/1 and UVPgt55. Seedling IT studies were conducted at least twice. Microsatellite analysis (4) showed that all single pustule isolates established from the original Matlabas isolate formed part of the Ug99 group. When characterized with selected single nucleotide polymorphisms (SNPs), all single pustule isolates shared an identical genotype that differed from UVPgt55 (TTKSF), a foreign introduction into South Africa (1,3). SNP genotype analysis suggests that UVPgt61/1 is genetically dissimilar to UVPgt55, as is Zim1009, another TTKSF+ isolate that was collected from Birchenough in Zimbabwe. Studies are underway to determine the identity of the defeated Sr gene in Matlabas and the cultivar has been added to the South African stem rust differential set. TTKSF+ is the eighth race detected in the Ug99 group. Since no other cultivars or advanced lines were found to carry the Matlabas gene, it is unlikely that race TTKSF+ will threaten wheat production in South Africa. However, the occurrence of a new Ug99-related race emphasizes the variability within this internationally important group. References: (1) W. H. P. Boshoff et al. Plant Dis. 86:922, 2002. (2) R. F. Park et al. Euphytica 179:109, 2011. (3) B. Visser et al. Mol. Plant Pathol. 10:213, 2009. (4) B. Visser et al. Euphytica 179:119, 2011.

Ovarian hyperstimulation syndrome is correlated with a reduction of soluble VEGF receptor protein level and a higher amount of VEGF-A.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening condition associated with increased vascular permeability. The vascular endothelial growth factor (VEGF) system and its receptors have been identified as the main angiogenic factors responsible for increased capillary permeability and are therefore discussed as crucial for the occurrence of OHSS. Recently, a number of soluble receptors for the VEGFs have been detected (sVEGF-Rs) and it has been shown that these sVEGF-Rs compete with the membrane-standing VEGF-R to bind VEGFs. METHODS: We analyzed the serum levels of soluble VEGF-R1, -R2 and -R3 in 34 patients suffering from OHSS and in 34 controls without this disease. In a subgroup analysis, we correlated the severity of the OHSS with the detected amounts of VEGF-R1, -R2 and -R3. In addition, we determined the amount of total VEGF-A in the samples. RESULTS: All the three soluble VEGF receptors tended to be higher in the control group compared with that in the OHSS group but this difference only reached significance for sVEGF-R2 (mean ± SEM: 15.5 ± 0.6 versus 13.8 ± 0.5 ng/ml, respectively, P< 0.05). In the subgroup analysis, sVEGF-R2 levels decreased as the severity of OHSS increased (OHSS-I: 16.8 ± 1.9 ng/ml and OHSS-III: 12.7 ± 1.0 ng/ml, P< 0.05) Moreover, the serum levels of total VEGF-A were higher in the OHSS group than those in the controls (537.7 ± 38.9 versus 351 ± 53.4 pg/ml, respectively P< 0.05). CONCLUSIONS: We propose that VEGF-A plays a role in the occurrence of OHSS, that the amount of biologically available VEGF-A is modulated by sVEGF-Rs and that different combinations of VEGF-A and sVEGF-R levels might contribute to the severity of OHSS.