Peste des petits ruminants infection in domestic ruminants in Sudan.

The existence of peste des petits ruminants (PPR) in domestic ruminants and camels in Sudan during 2008-2012 was investigated. Lung tissues and serum samples were randomly collected from sheep, goats, cattle, and camels at different areas of Sudan. A total of 12,384 serum samples were collected from clinically healthy 7413 sheep, 1988 camels, 1501 cattle, 1459 goats, and 23 gazelles at different areas in the Sudan. They were examined for PPR antibodies using competitive ELISA (cELISA). The overall detected seroprevalence of PPR in tested sera was 49.4%; seroprevalence values within species were 67.1, 48.2, 25.8, 2.1, and 21.7% in sheep, goat, cattle, camels, and gazelles, respectively. The highest seroprevalence (68.1%) was observed in sera collected from Darfur states, then the central states (54.3%). A total of 1276 lung tissue samples (623 sheep, 324 cattle, 220 camels, and 109 goats) were collected. The majority of lung samples were collected from clinically healthy animals that showed lesions on PM in slaughterhouses (95%) and during PPR outbreaks; samples were tested for PPR antigen using immunocapture ELISA (IcELISA). PPR antigen was detected in 233 out of the 1276 tested samples (18.3%). Positive results were observed in samples collected from clinically healthy and diseased animals. The observed prevalence values in each species were 33.6, 21.1, 15.4, and 12.3% in camel, goat, sheep, and cattle, respectively. PPR antigen was detected in samples from different areas; however, the highest prevalence (63.9%) was found in samples collected from the eastern states, then Khartoum state (28%). Trials for virus isolation were done in different cell cultures. Out of 30 IcELISA-positive samples inoculated in primary bovine and ovine kidney cells, Vero cells, the PPR virus was successfully isolated from 15 (eight sheep, five camels, and two goats) samples in the three cell culture types. Using RT-PCR, PPRV nucleic acid was detected in all 25 IcELISA-positive tested samples.

Altered expression of gap junction connexin proteins may partly underlie heart rhythm disturbances in the streptozotocin-induced diabetic rat heart.

Previous studies in isolated perfused heart and in atrial preparations have demonstrated significant reductions in beating rate in STZ-induced diabetic rats, which suggests that sinus arrhythmias in diabetes mellitus may be partly caused by intrinsic alteration of sino-atrial node (SAN) function. The effects of diabetes on electrical activity and expression levels of mRNA for gap junction proteins in the SAN have been investigated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) administered to young male Wistar rats (200-250 g). Experiments were performed 8-10 weeks after treatment. Conduction time and pacemaker cycle length were measured in sino-atrial node preparations with extracellular electrodes. Expression levels of mRNA for Gja5 (Cx40), Gja1 (Cx43) and Gja7 (Cx45) were measured in SAN and compared with right atrium and right ventricle with real-time quantitative reverse transcription-polymerase chain reaction. Diabetes was confirmed by a significant elevation of blood glucose (356+/-21 mg/dl) compared to age-matched controls (66+/-2 mg/dl). Pacemaker cycle length was significantly prolonged in diabetic heart (415+/-43 ms, n=6) compared to controls (255+/-7 ms, n=6). Sino-atrial conduction time was also significantly prolonged in diabetic hearts (12+/-2 ms) compared to controls (7+/-1 ms). Expression levels of mRNA for Gja5 (Cx40) and Gja1 (Cx43) were moderately increased and for Gja7 (Cx45) was significantly increased in SAN from diabetic heart compared to controls. Expression levels for gap junction connexin proteins were not significantly altered in right atrium or right ventricle from diabetic heart compared to controls. Structural remodelling of gap junction connexin proteins may partly underlie electrophysiological defects in STZ-induced diabetic rat SAN.

Expression of the oxytocin gene, but not the vasopressin gene, in the rat uterus during pregnancy: influence of oestradiol and progesterone.

Oxytocin (OT) and vasopressin (VP) are neurohypophyseal hormones with potent stimulatory actions on the uterus. In order to determine whether these hormones may have a paracrine action on the uterus, OT and VP gene expression was studied in myometrium from pregnant rats at gestational ages of 14 and 20 days, and from ovariectomized animals treated with oestradiol and progesterone. OT and VP mRNA concentrations were measured using real-time quantitative reverse transcription-PCR, and OT- and VP-like immunoreactivities were determined using RIA. OT mRNA was detected in the uterus from pregnant rats, but did not differ between the groups of different gestational ages. Oestradiol significantly (P<0.05) stimulated OT gene expression in ovariectomized rats. Progesterone alone was without effect on OT mRNA concentrations, but significantly (P<0.05) reduced the oestradiol-induced OT mRNA accumulation. The OT-like immunoreactivity in an extract of myometrium from pregnant rats was eluted from a reverse-phase HPLC column with a retention time identical to that of synthetic OT. Neither VP mRNA nor VP-like immunoreactivity was detected in the myometrium from pregnant or ovariectomized rats. The study demonstrates steroid-dependent expression of the OT gene in the rat uterus and processing of uterine preprooxytocin to the mature nonapeptide. The data support the theory that this peptide may act in a paracrine pathway. No evidence was found for the presence of VP in the uterus so that, if the hormone is involved in a stimulatory action on this tissue, it probably acts via an endocrine mechanism.

Invasive aspergillosis localised to the colon presenting as toxic megacolon.

Primary gut involvement by Aspergillus is an exceedingly rare and often a fatal complication of intensive chemotherapy in patients with acute leukaemia. We report a 46-yr-old patient with granulocytic sarcoma of the testis. He received acute myeloid leukaemia type treatment with ADE chemotherapy (Cytosine Arabinoside, Daunorubicin and Etoposide). While neutropenic he presented with pyrexia, abdominal pain and massive abdominal distention. He was treated with intravenous antibiotics and antifungals according to our usual institutional protocol without any response. He was found to have toxic megacolon on plain X-ray and subsequently underwent total colectomy and ileostomy. The colon histology showed Aspergillus fungal hyphae infiltrating the bowel wall. There was no any evidence of pulmonary, hepatic, splenic or renal lesions on the computerised tomography scan. Following colectomy, he was treated with 2 wk of antifungal treatment. He recovered well and was discharged home. The increased awareness, high degree of clinical suspicion of unusual presentation and early surgical intervention with aggressive antifungal treatment, has a key role in the management of these rare and often fatal cases.

Cefotaxime as the potential cause of transient acquired von Willebrand syndrome.

Acquired von Willebrand syndrome (AvWS) is a relatively rare bleeding disorder. It has been reported in association with myeloproliferative disorders, autoimmune diseases, plasma cell dyscrasias and certain drugs. Cefotaxime is a third generation cephalosporin widely used for surgical prophylaxis and as empirical treatment of bacterial meningitis. We report a case of a transient AvWS in association with cefotaxime therapy.

Test analytes for studies of the molecular mechanism of chromatographic separations by quantitative structure-retention relationships.

Three model series of nonionized in water analytes are proposed for objective interlaboratory comparisons of effects on chromatographic separations of the stationary and the mobile phases by means of the analysis of quantitative structure-retention relationships (QSRR). Each series was designed specifically for a given general QSRR model by selecting the analytes whose properties were well reflected by the respective structural descriptors. Rules of a meaningful chemometric analysis were observed, and the structural information content was compromised with the length of analyte series. Three QSRR models were verified and are recommended for studies of molecular mechanism of chromatographic retention: the reduced linear solvation energy relationship-based model of Abraham, a model employing structural descriptors from molecular modeling, and a model correlating retention to the 1-octanol-water partition coefficient, log P. All the models were demonstrated to provide reliable QSRR equations for five sets of diverse retention data. These equations discriminate quantitatively individual chromatographic systems and are interpretable in straightforward chemical categories. In view of QSRR analysis, the retention processes clearly emerge as the net effects of fundamental intermolecular interactions involving the analyte and the components of chromatographic systems.

Fibrinolytic changes in a patient with toxic shock syndrome; release of active u-PA.

OBJECTIVE: Definition of the changes in the activators of plasminogen, u-PA and t-PA, and examination of the possible generation of plasmin in the circulation in overwhelming sepsis. DESIGN: Serial blood analysis starting 4 h after development of symptoms of toxic shock syndrome. SETTING: Intensive care unit. PATIENT: A previously healthy woman underwent endometrial ablation and rapidly thereafter developed staphylococcal toxic shock syndrome with organ failure. MEASUREMENT AND RESULT: t-PA, PAI-1, t-PA-PAI-1 complexes, plasminogen, fibrinogen and plasmin-alpha 2-antiplasmin complexes were measured serially by ELISA and free u-PA by SDS-PAGE with zymography. The onset of symptoms was accompanied by a rise of t-PA antigen-followed rapidly by PAI-1 antigen. Plasmin-alpha 2-antiplasmin complex was generated in large amounts but disappeared within hours. From day 3, free u-PA was detectable in the circulation without plasmin generation. CONCLUSION: Despite the sustained presence of active u-PA in the circulation and of t-PA antigen at the onset of symptoms, plasmin-alpha 2-antiplasmin generation was largely suppressed by high levels of PAI-1. The suppression of plasmin generation by u-PA and t-PA may ensure the persistence of fibrin in the microcirculation and so contribute to organ failure.

Mechanism of separation on cholesterol-silica stationary phase for high-performance liquid chromatography as revealed by analysis of quantitative structure-retention relationships.

The retention characteristics of a newly synthesized stationary phase were determined for reversed-phase high-performance liquid chromatography obtained by chemical immobilization of cholesterol on spherical silica gel. For a designed series of analytes the retention factors, log k, were determined at several compositions of the methanol-water mobile phase. Logarithms of retention factor corresponding to a hypothetical pure water eluent, log k(w), were calculated by extrapolation of the linear relationships of individual log k data versus volume percent of methanol. The series of 24 test analytes were characterized structurally by means of the logarithms of n-octanol-water partition coefficients, log P, by a set of the linear solvation energy relationship (LSER)-based descriptors of the polarity and bulkiness of the analytes and by structural descriptors of analyte size and polarity acquired by molecular modelling. Quantitative structure retention relationships (QSRR) were derived by multiple regression analysis using the three groups of structural descriptors of analytes and the log k(w) data determined on the new stationary phase. For the sake of comparison the corresponding QSRR equations were also derived for retention parameters determined on a standard octadecylsilica and on the so-called immobilized artificial membrane (IAM) stationary phase. The QSRR analysis clearly proved distinctive retention properties of the new cholesterol-silica stationary phase. It has been concluded that the new phase may possess valuable analytical specificity. Its application for modelling penetration of xenobiotics through biological membranes appears rather unlikely.

Inhibitors of plasminogen activator in neutrophils and mononuclear cells from septic patients.

Leucocytes, both polymorphs and mononuclear cells, play a variety of roles in the evolution of human response to sepsis, both local and generalised. In this study, inhibitors of plasminogen activator were measured in leucocytes from normal and septic patients. Plasminogen activator inhibitor-1 (PAI-1) was identified in polymorphs from normal individuals and levels rose significantly in polymorphs from septic patients: neutrophils from normal subjects did not contain PAI-2 but this protein was detectable in significant quantities in polymorph preparations from septic patients. In contrast, mononuclear cells from normal and septic patients contained no detectable quantities of PAI-1. Significant amounts of PAI-2 were present in normal mononuclear cells, and the levels rose significantly in monocytes from septic patients. PAI-2 is thus here identified in human subjects, distinct from those with pregnancy or malignancy, as playing a role in a pathological process. The increased levels of both inhibitors produced by leucocytes may clearly contribute directly to the persistence of fibrin, a characteristic feature of the response to infection, local or general; they may thus participate in successful localisation of infections (abscess formation etc.) and in the evolution of the major systemic complications of disseminated sepsis characterised by microvascular occlusion by fibrin such as renal failure, shock lung or digital ischaemia.

Influence of white blood cells on the fibrinolytic response to sepsis: studies of septic patients with or without severe leucopenia.

In septic patients capable of normal white cell responses, high plasma levels of PAI-I, t-PA antigen and t-PA-PAI-I complex were observed. The ratios of t-PA and PAI-I were such that free PA activity was almost never observed. In patients severely leucopenic prior to becoming septic the changes were significantly less marked, so presence of leucocytes enhances the fibrinolytic inhibition occurring in sepsis. The non-leucopenic septic group showed greater evidence of thrombin generation in that FPA levels were higher but fibrinogen levels were only slightly less and antithrombin levels not different from those in the leucopenic group. A greater tendency to fibrin deposition and the striking fibrinolytic inhibition noted in patients with normal white cell responses may contribute to the development of some of the complications of sepsis in which fibrin deposition participates and may explain their relative rarity in leucopenic patients. When shock supervened, levels of PAI-I were high in both leucopenic and non-leucopenic groups, indicating that a source of PAI-I outwith the leucocytes themselves contributes to the phenomena observed.