1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D-galactofuranosidase inhibitors

Beta-D-galactofuranosidase is a good chemotherapeutic target for the design of inhibitors, since beta-D-galactofuranose is a constituent of important parasite glycoconjugates but is not present in the host mammals. With this aim, we have synthesized for the first time alkyl, benzyl and aryl 1-thio-beta-D-galactofuranosides by condensation of penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols, in the presence of SnCl4as catalyst. The complete chemical and spectroscopical characterization of these compounds showed that the reaction was stereoselective. Debenzoylation with sodium methoxide afforded the beta-S-galactofuranosides in high yield. The thioglycosides were tested as inhibitors of the beta-D-galactofuranosidase of Penicillium fellutanum, using for the first time 4-nitrophenyl-beta-D-galactofuranoside as chromogenic substrate. The 4-aminophenyl-1-thio-beta-D-galactofuranoside, obtained by catalytic hydrogenation of the nitrophenyl derivative, was the best inhibitor being then an adequate ligand for the preparation of an affinity phase aimed at the isolation of beta-d-galactofuranosidases from different sources. Also the inhibitory activity of d-galactono-1, 4-lactone was shown.     

Infectious complications occurring in liver transplant recipients receiving mycophenolate mofetil

PURPOSE: To determine the causes of visual impairment in a population-based group of visually impaired preterm children. METHODS: Ophthalmological examination and magnetic resonance imaging or computed tomography of the brain were performed in all visually impaired preterm children born 1989-95 in V?rmland. RESULTS: Ten of 18 children had periventricular leukomalacia affecting the optic radiation, six had other lesions or malformations in the posterior visual pathways/cortex, but no child had visually impairing retinopathy of prematurity. CONCLUSION: We conclude that cerebral lesions or malformations are common causes of the visual functional deficit in visually impaired children born preterm. Brain damage should be suspected in a prematurely born child who presents with either of the signs: fixation difficulties, strabismus or nystagmus.     

Cavo-pulmonary anastomosis associated with intracardiac repair of Ebstein anomaly. Value in high-risk patients]

The cyclin-dependent kinase inhibitor p27Kip1 controls cell proliferation in response to normal mitogenic stimuli. We show here that p27Kip1 also safeguards against excessive cell proliferation in specific pathophysiologic settings. We used experimental glomerulonephritis as a paradigm for immune mediated inflammation and ureteral obstruction as a model for non-immune mediated inflammation. Renal function was substantially decreased in nephritic p27-/- mice compared with control mice, and this was associated with increased glomerular cell proliferation, apoptosis and matrix protein accumulation. Tubular epithelial cell proliferation and apoptosis was also increased in p27-/- mice following ureteral obstruction. p27Kip1 may have a general role in protecting cells and tissues from inflammatory injury.     

Activation of the Na+-K+(NH4+)-2Cl(-)- cotransporter from rat submandibular glands in response to VIP

A cellular suspension from rat submandibular glands was prepared with collagenase. The intracellular pH (pHi) was estimated with 2',7'-bis-(2-carboxy-ethyl)-5(6)-carboxyfluorescein (BCECF). After exposure to NH4Cl, the pHi transiently increased (diffusion of NH3) and then dropped (influx of NH4+). Isoproterenol increased 2.5-fold the rate of NH4+ influx; bumetanide, an inhibitor of the Na+-K+-2Cl(-)-cotransporter blocked the response to isoproterenol, confirming that the beta-adrenergic agonist stimulated the cotransporter. Forskolin (1 micromol/L) mimicked the response to isoproterenol. VIP (1 nmol/L(-1) micromol/L) also increased the activity of the cotransporter. Cyclic AMP rather than calcium was the mediator of this activation since 1) carbachol which increased the [Ca2+]i fivefold increased the uptake of NH4+ by only 50%; 2) only high concentrations of VIP significantly increased the [Ca2+]i; 3) incubation in the presence of EGTA had no effect on the response to VIP; 4) low concentrations (nmol/L) of the neuropeptide increased the intracellular level of cAMP; and 5) the stimulation of the cotransporter by VIP, forskolin, and isoproterenol was inhibited by H8, an inhibitor of cAMP-dependent protein kinase. It is concluded that the Na+-K+-2Cl(-)-cotransporter of rat submandibular glands is activated by isoproterenol, forskolin, and neuropeptides of the VIP family by a mechanism involving cAMP-dependent processes. The activation of the cotransporter by VIP could partly explain the potentiating effect of VIP on the response to sialagogues like substance P or muscarinic agonists.     

Photorefractive gratings in DR1-doped hybrid sol–gel films

Photorefractive gratings have been obtained with 632.8 nm writing beams in organic–inorganic SiO₂-based films. The hybrid glass is prepared by a sol–gel technique, starting from organic Si precursors, and contains Disperse Red 1 (DR1), carbazole units and 2,4,7-trinitro-9-fluorenone (TNF). The photorefractive gain, which has been found unexpectedly even without poling field, has been determined through an asymmetric energy exchange by two-beam coupling measurements. The effects of the polarization of the writing beams and of a circularly polarized photoisomerizing radiation during the erasure of the grating have been interpreted in terms of an orientational contribution to the grating formation.     

Acromioclavicular joint cyst and rotator cuff tear

The role of a depressor factor, atrial natriuretic peptide, in the development of arterial hypertension in adolescents with pubertal hypothalamic syndrome was studied in 52 patients and 13 healthy males aged 13-24 years. The duration of disease was 2-11 years. Radioimmunological methods were used to measure plasma atrial natriuretic peptide, plasma renin activity, and serum aldosterone. Patients with borderline arterial hypertension were found to have a significant reduction in their atrial natriuretic peptide levels, and this correlated directly with the renin-aldosterone system, demonstrating insufficiency of the depressor system in patients with pubertal hypothalamic syndrome and the involvement of atrial natriuretic peptide in the development of arterial hypertension, along with disturbances in the functional relationship between atrial natriuretic peptide and the renin-aldosterone system.     

Hepatitis C virus genotypes in liver transplant recipients: impact on posttransplant recurrence, infections, response to interferon-alpha therapy and outcome

BACKGROUND: End-stage liver disease due to hepatitis C virus (HCV) is the most common indication for liver transplantation in U.S. veterans. We investigated the influence of HCV genotypes on the incidence and timing of recurrent HCV hepatitis, survival, infectious morbidity, and response to interferon-alpha therapy in this unique patient population. METHODS: HCV genotype was determined by direct sequencing of the NS5 region of HCV with type-specific primers. RESULTS: Genotype 1a (66%, 32/47) was the predominant genotype. Type 1b was found in 25% (12/47) of patients and type 2b was found in 9% (4/47). Histopathologically recurrent HCV hepatitis developed in 53% (25/47) of the patients after transplantation. This group included 45% (14/31) of the patients with type 1a, 67% (8/12) of the patients with type 1b, and 25% (1/4) of the patients with type 2b (P>0.5). The time to recurrence and the severity of HCV recurrence as defined by aminotransferase levels or Knodell scores were not different among the three genotypes. There was a trend toward a higher incidence of major infections in patients with type 1b (75%) versus type 1a (48%) and type 2b (50%) (P=0.11). The response to interferon-a therapy did not differ significantly among the genotypes. Mortality at 5 years was 16% (5/31) in patients with genotype 1a, 42% (5/12) in patients with genotype 1b, and 50% (2/4) in patients with genotype 2b (P=0.06). CONCLUSIONS: The incidence, time to recurrence, and response to interferon-alpha therapy did not differ between the various genotypes in our liver transplant recipients. However, there was a trend toward higher infectious morbidity and overall mortality in patients with genotype 1b after transplantation.     

Human herpesvirus-6 infection in liver transplant recipients: documentation of pathogenicity

In the posterior partially edentulous jaw, implants may be used to supplement existing natural dentition. Frequently, the maxillary sinuses and the mandibular nerve preclude the fabrication of freestanding implant-retained prostheses. However, if an implant and a natural abutment are combined, a fixed prosthesis can be fabricated, restoring the arch into the premolar area. The histories of three patients with attachments connecting implant-retained ceramotitanium crowns with crowns on natural abutments are described. A design for a rigid custom-made attachment for the Br?nemark system, using standard components with a machine-duplication, spark-erosion technique, is suggested.     

Spreading of a Gravity Current over a Permeable Surface

Plane inertial gravity currents running over horizontal permeable surfaces are studied. An analytical simple model based on local and global balances is derived which describes the propagation and infiltration of an incompressible dense fluid on and through the surface. Results of laboratory experiments are presented which are in accordance with scaling laws suggested analytically. It is found that the loss of mass, the velocity, and the position of the front of the current follow exponential relationships. The dynamics is governed by a particular decay time related to the initial volume released and reduced gravity g0′. However this decay time exhibits a different functional relationship from that obtained for currents evolving over thin permeable bottoms when the downward flow is viscous. As a consequence of the loss of mass, the distance to extinction of the current is found to be independent of g0′.     

History of urethral catheters and their balloons: drainage, anchorage, dilation, and hemostasis

Male urethral catheterization, as practiced in early Greece, was made possible by a sound knowledge of anatomy. It has been preserved by written tradition and advanced by the development of new materials. Balloon dilation, conceived and practiced more than 160 years ago by urologists, has undergone a similar cycle. Some useful ideas, once conceived, have been forgotten and have surfaced again, decades, sometimes centuries, later as new inventions.