Search

A series of derivatives of 4-hydroxycyclohexanone (1a–g) with the hydroxy group protected as a silyl ether (1a, b), ether (1d, g), an acetal (1c), or an ester (1e, f) were deprotonated with chiral,...

Lithium dienolate of verbenone reacts with aromatic aldehydes to give α- and γ-aldols. Unusual features of the reaction include: selective formation of the γ-aldols under kinetic conditions, absence of deconjugated α-products, high sensitivity to electronic effects and formation of bis-aldols 5.

(1995). SYNTHESIS OF 1,3-DIMETHYLAZULENE. Organic Preparations and Procedures International: Vol. 27, No. 5, pp. 592-595.

Enantioselective synthesis of two butenolides (4 S , 6 R )-2,3-Dihydroaquilegiolide and (4 S , 6 S )-2,3-Dihydromenisdaurilide based on deprotonation of 4- tert -butyldimethylsiloxy-cyclohexanone with a chiral lithium amide base is described.

Enantioselective deprotonation of tropinone 2 with chiral lithium amides 5a and 6a, in the presence of LiC1, gave tropinone lithium enolate in up to 95% ee. The CZ symmetrical lithium amide 6a worked best when it was generated in situ from the hydrochloride salt of the corresponding amine 6b. The deprotonation was used as the key step in synthesis of tropane alkaloids: entanhydroecgonine, ent-knightinol, KD-B, chalcostrobamine, ent-isobellendine, and ent-darlingine. The absolute configuration of natural benzyltropane and pyranotropane alkaloids was established (by correlation with anhydroecgonine) to be ‘cocaine-like’ i.e., the side chain originates at C-2 of the tropane ring system in all cases.

The lithium enolate of tropinone reacts with alkyl chloroformates to give 6-N-carboalkoxy-N-methyl-2-cycloheptenones (4). These compounds can be produced enantioselectively, in up to 95% ee, if chi...

Three diastereoisomers of 1-deoxycastanospermine were synthesized in enantiomerically pure form. The key step in the synthesis involved reaction of lithiated N-Boc-pyrrolidine in the presence of sparteine with a chiral building block derived from tartaric acid.

Alkylation of the SAMP hydrazone of 1,3-dioxa-5-one provides a convenient way (8 steps, 40% overall yield) to synthesize frontalin in high optical purity (over 95%).

Tropinone (6) was deprotonated with lithium diisopropylamide and with chiral lithium amides (18–24) and the resulting enolates (two enantiomers) were treated with electrophiles. The aldol reaction with benzaldehyde and deuteration were both diastereoselective. The former yielded only one isomer (exo, anti) of the aldol 8a; the latter proceeded from the exo face. This selectivity permitted us to probe the deprotonation of tropinone with lithium amides; it was concluded that the reaction involves predominantly the exo axial protons. The reaction of tropinone enolate with ethyl chloroformate led, via a ring opening, to the cycloheptenone derivative 9. The reaction with methyl cyanoformate yielded, in the presence of silver acetate and acetic acid, the β-ketoester 8b; however, in the absence of these additives, and especially when 12-crown-4 was added to the enolate, a ring opening leading to the pyrrolidine derivative 10 occurred instead. Deprotonation of tropinone with chiral lithium amides proceeded with modest enantioselectivity. A synthesis of non-racemic anhydroecgonine via this strategy allowed establishing the absolute stereochemistry of deprotonation.

Deprotonation of cis-3,5-dimethylcyclohexanone (6) with chiral lithium amide bases has been investigated. The resulting lithium enolates react with benzaldehyde, acetic anhydride, or trimethylsilyl chloride. Effects of solvents and additives on the selectivity of these reactions have been studied

Camphene oxide reacted with dilithiated o-methoxy-phenylacetic acid to yield selectively the exo isomer of a spiro[γ-lactone-2,2′-bicyclo[2.2.1]heptane] which was stereoselectively converted into the exo-3,4-dihydrospiro[2H-1-benzopyran-2,2′-bicyclo[2.2.1]heptane].

The reaction of lithium dienolates derived from N,N-dialkylsenecioamides (1a–1c) with triorganosilyl electrophiles occurs initially at the oxygen atom predominantly, and is followed by an O → C sil...

In the first part of the paper, we prove a generalization of the classical Poincare-Miranda theorem to the case of a denumerable set of continuous functions of denumerable number of variables. The second part of the paper concerns the controllability of nonlinear repetitive processes. First, we formulate a theorem on the existence of a unique solution to such process and theorem on the continuous dependence of solutions on controls. Next, we use the obtained generalization of Poincare-Miranda theorem to prove a result on the controllability of nonlinear repetitive process.

We report a new protocol for synthesis of L-1-deoxymannojirimycin, L-1-deoxyidonojirimycin, and the N-isopropyl derivative of the latter compound from the readily available precursors (S)-isoserinal hydrate and 2-tert-butyl-2-methyl-1,3-dioxan-5-one. The key steps include diastereoselective proline-catalyzed syn aldol transformation and a reductive amination/cyclization.

L’histoire naturelle des anevrysmes de l’aorte abdominale sous-renale (AAA) est marquee par une augmentation progressive de taille (environ 4 mm par an). Le risque de rupture depend principalement du diametre anevrysmal. Lorsque le diametre est compris entre 5 et 5,9 cm, le risque de rupture est de 11% par an et il s’eleve a plus de 25% au-dela de 6 cm (1). Ainsi, la rupture d’AAA est actuellement responsable de 1 a 2% des deces des hommes âges de plus de 65 ans dans les pays industrialises (2).

La rupture d’un anevrysme de l’aorte abdominale ou de l’artere iliaque (AAIR) est grevee d’un taux de mortalite spontane de plus de 80% (1). La «mise a plat greffe chirurgicale» de l’anevrysme est le traitement de reference des AAIR mais le taux de mortalite de cette intervention rapporte par une meta-analyse sur 171 etudes compilees depuis 1955 est de 48% (2).

In the article, 17-year-old girl with iatrogenic severe hipercalcemia was presented. The girl was treated since the age of 12 years for steroid-sensitive minimal change disease. Due to steroid therapy osteoporosis developed and intensive treatment with active form of vitamin D and high doses of calcium was started. She was admitted to our clinic in severe general state with abdominal pain, vomiting, dehydration, muscle weakness, hypertension and mental confusion. Severe hipercalcemia with nephrocalcinosis was diagnosed. The history revealed that the girl had increased the doses of drugs intentionally. The authors emphasized the need for careful monitoring of prophylaxis and treatment for osteoporosis due to steroid therapy.

The purpose of the study was to analyze treatment approaches in children with malformations of urinary system. The retrospective study comprised 557 children (196 boys and 361 girls) aged 1-18 years with malformations of urinary system hospitalized in 2000-2007 in the Department of Pediatric Nephrology, University Children's Hospital, Lublin. Primary and secondary vesicoureteral reflux (269 children), ureteral obstruction (102 children), urethral obstruction (91 children) and renal duplication (83 children) were the most common malformations observed. In 26 children, multiple urinary system malformations were diagnosed. 332 children required surgery including 113 with vesicoureteral reflux. However, in the majority of children with vesicoureteral reflux, on an average 18-month pharmacologic treatment resulted in complete recovery.

Nephrocalcinosis (NC) is defined by increased calcium content of the kidney. To be identified radiologically it must be substantially gross accumulation of calcium within renal tissue. The incidence of NC in children is very low. The main causes of NC are hypercalcemic states with hypercalciuria and various tubular disorders. Although renal calcification may induce interstitial and tubular damage, NC is relatively rare associated with renal failure. We present three children with such an association. In those patients, primary distal tubular acidosis, hyperoxaluria type I and familial hypomagnesemia with hypercalciuria and nephrocalcinosis were diagnosed. The former two patients developed terminal renal failure in the school age whereas in the latter one, only moderate renal insufficiency was observed.The coexistence of nephrocalcinosis and renal failure is caused by extremely rare metabolic disorders. Therefore, this condition requires careful examinations.

Aromatic aldehydes add to β-pinene under Lewis acid catalyzed Prins reaction conditions and yield the corresponding homoallylic alcohols. The reactions proceed in poor yield when electron donating substituents are present on the aromatic ring.

In the paper sufficient conditions for the controllability to the interval of two-dimensional continuous Roesser system and one-dimensional continuous system are proved. The idea of proof is based on applying a lemma which is a multidimensional version of Bolzano-Poincare theorem.

Little is known about how the immune system impacts human colorectal cancer invasiveness and stemness. Here we detected interleukin-22 (IL-22) in patient colorectal cancer tissues that was produced predominantly by CD4+ T cells. In a mouse model, migration of these cells into the colon cancer microenvironment required the chemokine receptor CCR6 and its ligand CCL20. IL-22 acted on cancer cells to promote activation of the transcription factor STAT3 and expression of the histone 3 lysine 79 (H3K79) methytransferase DOT1L. The DOT1L complex induced the core stem cell genes NANOG, SOX2, and Pou5F1, resulting in increased cancer stemness and tumorigenic potential. Furthermore, high DOT1L expression and H3K79me2 in colorectal cancer tissues was a predictor of poor patient survival. Thus, IL-22+ cells promote colon cancer stemness via regulation of stemness genes that negatively affects patient outcome. Efforts to target this network might be a strategy in treating colorectal cancer patients.

We present a 5-years old boy with acquired Fanconi-de Toni-Debre syndrome being a effect of therapy for Ewing's sarcoma. At the age of 3 years, this boy was diagnosed as suffering from Ewing sarcoma of his right femur. The boy received a course of 8-month pre-surgery (6 VIDE--Vincristine, Ifosfamide, Doxorubicin, Etoposide cycles and 2 VAI--Vincristine, Actinomycin, Ifosfamide cycles) and 6-month post-surgery (6 VAI--Vincristine, Actinomycin, Ifosfamide cycles) cytostatic therapies according to EWING, EURO 99 protocol. In forth month of post-surgery cytostatic therapy, progressive malaise, polyuria, polydypsia, and recurrent vomiting occurred. The association between those symptoms and malignancy was excluded. Laboratory studies revealed hypokaliemia, hypophosphatemia, proximal tubular acidosis, proteinuria, glucosuria, aminoaciduria, hyperkaliuria and hyperphosphaturia. Acquired Fanconi-de Toni-Debre syndrome due to toxic effect of cytostatic therapy on renal proximal tubules was diagnosed. At present, two years after the time the diagnosis was made, despite constant substitution of potassium, phosphates and bicarbonates, deficit of body mass and height, and bone mineral density abnormalities are observed.

Since January 26th of 1996, when our center was established, 34 children (19 boys and 15 girls) with end-stage renal disease (ESRD) were treated with renal replacement therapy. Maintenance hemodialysis (HD) and peritoneal dialysis (PO) were received by 28 and 6 patients, respectively. In our patients, the most common cause of ESRD were congenital urinary system malformations (61.7%) and glomerulonephritides (20.6%). Duration of renal replace-ment therapy varied from 6 months to 8 years. In 71.5% of children on HD, vascular access was established by arteriovenous fistula, and in the remaining--by permanent venous catheter. Adequacy of renal replacement therapy was estimated by Kt/V ratio. In patients on HD and PO, Kt/V ratios were 1.27 and 1.9 per 7 days, respectively. In 82.4% of patients, pre-dialysis arterial hypertension was observed. During renal replacement therapy arterial hypertension was diagnosed in 73.5% of children. Anemia resulting from ESRD was treated with recombinant human erythropoietin and erythropoietic medicines. In all children, recommended hemoglobin and hematocrit levels were achieved. In our patients, parameters of calcium and phosphate handling were also monitored. The mean serum intact parathormone levels in HD and PO children were 304 pg/ml and 302.2 pg/ml, respectively. We also summarized the occurrence of hepatotropic viral infections and endocrine disturbances including hypothyreosis and short stature in our patients. 3 children died due to ESRD complication. 22 (64,7%) children received cadaver-donor renal transplants.

Citrate is thought to be one of the most important inhibitor of calcium salts crystallization in the urine. Therefore, an assessment of urinary citrate excretion is an integral element of metabolic evaluation in urolithiasis. The reported incidence of urolithiasis associated with hypocitraturia varies from 10% to 63%. The purpose of the study was to assess urinary citrate excretion in children with calcium urolithiasis living in region of Lublin. The study comprised 60 children (34 boys and 26 girls) aged 4.3-18 years. In 36 of them, calcium oxalate urolithiasis was diagnosed by spectrophotometry. In the remaining children, an assessment of stone composition was impossible. However, in all children, stones were radiopaque. Hypercalciuria (HC) and mild hyperoxaluria (HOx) were diagnosed in 23 and 16 children, respectively. In the remaining 21 children urolihiasis was classified as idiopathic. The controls were 35 healthy age- and gender-matched children. Urinary citrate excretions were assessed by enzymatic method in 24-hour urine specimens and expressed as citrate/creatinine ratios (Cit/Cr). Decreased Cit/Cr were observed in 9 (15%) children with calcium urolithiasis. However, there was no significant difference between the mean Cit/ Cr in children with calcium urolithiasis and controls (410 +/- 207 mg/g vs 385 +/- 144 mg/g). There was also no significant difference between the mean Cit/ Cr in children with HC and controls. Similarly, the mean Cit/Cr did not differ significantly between children with HOx and controls. However, the lowest mean Cit/Cr was revealed in children with HOx (306 +/- 161 mg/g).In most children with calcium urolithiasis urinary citrate excretion was normal. However, in some children with urolithiasis, detection of hypocitraturia allows to explain pathogenesis of stone formation and to carry on a causative prophylaxis.

Reflux nephropathy is a progressive renal scarring due to chronic pyelonephritis developing in patients with vesico-ureteral reflux. TGF-beta1 is thought to be one of the most important factor that initiates reflux nephropathy and stimulates its progression. The purpose of the study was to assess serum TGF-beta1 level in children with reflux nephropathy. The study comprised 36 children (12 boys and 24 girls) aged 1-17 years with vesicoureteral reflux and renal scarring confirmed by scintigraphic evaluation. In most children recurrent urinary tract infections were observed. In 13 (27.8%) children, a first episode of urinary tract infection occurred in infancy. Primary vesico-ureteral reflux was diagnosed in 18 (50.0%) children. Secondary vesico-ureteral reflux due to anatomic or functional subvesical obstruction were recognized in 11 (30.6%) and 7 (19.4%) children, respectively. Serum TGF-beta1 levels were measured by ELISA. The mean serum TGF-beta1 level in children with reflux nephropathy was significantly lower than that in controls (92.04 +/- 33.14 ng/ml vs 141.73 +/- 45.38 ng/ml). This might be a result of increased influx of serum TGF-beta1 into renal parenchyma and/or increased urinary TGF-beta1 excretion due to tubular damage in children with reflux nephropathy.

The purposes of the study were a) to assess the incidence of urinary system malformations in children with the nephrotic syndrome (NS) and b) to estimate their effect on clinical course of the NS. A retrospective analysis comprised medical records of patients aged 2-18 years hospitalized in the Department of Pediatric Nephrology, University Children's Hospital, Lublin. Urinary tract infections (UTI) occurred in 28% of children with the NS. Imaging evaluation revealed urinary system malformations in 21.2% of children with the NS and UTI. Urinary system malformations constituted 5.9% of all children hospitalized because of the NS. Urinary system malformations included vesico-ureteral reflux (42.8%), renal duplication (28.6%), renal agenesis (14.3%) and diverticulum of the bladder (14.3%). In 48% of children with the NS and urinary system malformations, frequent recurrences of the syndrome were observed.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubulopathy resulting from mutation in the gene encoding paracelin 1. The main symptoms of FHHNC include excessive urinary calcium and magnesium excretion, nephrocalcinosis, and chronic renal failure. We present 16-year old girl in whom symptoms of FHHNC were accidentally recognized during therapy of acute lymphoblastic leukemia. In our patient, some symptoms of FHHNC were initially taken for the adverse effects of cytostatic therapy that delayed an adequate diagnosis. To the best of our knowledge, this is the first report of FHHNC associated with acute lymphoblastic leukemia. However, in our opinion this association is accidental.

Objectives: The purpose of this clinical trial was to explore whether lubiprostone increases the rate of mucus and mucin secretion and its viscosity in chronic constipation (CC) patients. The secretion of chloride (CS) into the gastrointestinal tract lumen is pivotal in the body's ability to process non-digestible food components. CS sets the optimal rate of hydration for non-digestible food components, their fluidity, and their adequate propulsion along the alimentary tract. Chloride is also instrumental in the secretion of alimentary tract mucus, and the formation of a gel-like, viscous mucus-buffer layer. This layer acts as the first line and vanguard of the mucosal barrier. This barrier is essential in mucosal lubrication and protection. Lubiprostone, a novel chloride channel stimulator ClC-2, is currently approved for the treatment of CC. Its impact on mucus, mucus secretion, and viscosity is not established. Methods: A double-blind, crossover trial was approved by the IRBs at the Kansas University Medical Center (Kansas City, KS) (study site) and at the Texas Tech University HSC (El Paso, TX) (analysis site). The study included 20 patients (17 females (F); mean age: 37 years) with symptoms of CC diagnosed according to the Rome III criteria. Patients were randomized to 1 week of therapy with lubiprostone or placebo followed by a 1 week washout and 1 week of the alternative therapy. Gastric juice was collected basally and during stimulation with pentagastrin (6 μg/kg body weight subcutaneously) at the end of weeks 1 and 3. Pentagastrin stimulation mimics food stimulation. The mucus content in gastric juice was assessed gravimetrically. The mucin content was measured after its purification using ultracentrifugation. The viscosity of the gastric secretion was measured using a digital viscometer. Results: In comparison with placebo, the volume of gastric secretion in patients with CC during administration of lubiprostone increased significantly by 50% (86.3 vs. 57.5 ml/h) (P

The purpose of the study was to assess the intensity of lymphocyte T apoptosis in nephrotic children's peripheral blood before, during and after the treatment with prednisone. The percentages of apoptotic lymphocyte T were determined by flow cytometry using annexin V. The study comprised 26 nephrotic children aged 3-14 years. The controls were 15 healthy children. In acute phase of the nephrotic syndrome before institution of the therapy the mean percentage of apoptotic lymphocytes T was 2.61%. It was significantly higher than that in controls (1.08%). During treatment with prednisone a statistically significant increase in the mean percentage of apoptotic lymphocytes T was observed. After four-week therapy with prednisone and after completion of the treatment the percentages of apoptotic lymphocytes T were 7.96% and 9.51%, respectively. They were significantly higher than those in patients before treatment and in healthy children.

The aim of the study was the retrospective analysis of the results of the drug sensitivity studies of bacterial species cultured from 681 urinary specimens collected from 79 children (12 boys and 67 girls) aged 0-18 years with recurrent urinary tract infection in a period from 1997 to 2001. Factors predisposing to recurrent urinary tract infections and the incidences of particular uropathogens were also analyzed. Escherichia coli (57.3%), Proteus spp. (15.6%) and Pseudomonas aeruginosa (9.1%) were the most frequent isolated pathogens. Reinfections and relapses of urinary tract infections were observed in 74.7% and 25.3% of the children, respectively. In some children etiologic variability of particular infection episodes were observed. In the majority of the children infection episodes were caused by one or two bacterial species and new infections differed from previous ones only in drug sensitivity. In 30 children vesicoureteral reflux was detected. Other anatomical abnormalities of urinary tract were revealed in 17 children. In 18 children, neurogenic bladder dysfunction was diagnosed. Urodynamics disclosed functional abnormalities in 48/55 children.

The purpose of the study was to determine: a) the incidence of particular symptoms of dysfunctional voiding, b) the incidence of particular urodynamic disorders, and c) urodynamic patterns typical of particular symptoms of dysfunctional voiding in children with recurrent urinary tract infection. The study comprised 282 children with recurrent urinary tract infection. In order to diagnose functional disturbances of the lower urinary tract, such as detrusor instability, detrusor-sphincter dyscoordination, detrusor instability associated with detrusor-sphincter dyscoordination, and functional subvesical obstruction, in all children, urodynamic examination was performed. For each symptom of dysfunctional voiding (nocturnal enuresis, diurnal urinary incontinence, urinary urgency, and voiding postponement syndrome) urodynamic pattern was determined. The study revealed that functional disturbances of the lower urinary tract coexist with positive histories of micturition disturbances. In the studied children, detrusor instability was the most common urodynamic disorder. Nocturnal enuresis, diurnal urinary incontinence and urinary urgency were symptoms of dysfunctional voiding typical of detrusor stability. In children with and without vesico-ureteral reflux, the incidences of particular urodynamic disorders were similar. This seems to suggest that disturbances of the lower urinary tract may be secondary to infection.

The purpose of the study was to estimate the efficacy of vaccination against viral hepatitis type B in children with the nephrotic syndrome and to estimate the probable cause-effect relationship between the occurrence of the nephrotic syndrome and infectious diseases and vaccination in children. The retrospective study comprised 235 nephrotic children aged 1-14 years hospitalized in the Department of Pediatric Nephrology at University Children Hospital, Lublin, between 1982 and 1997. 56 nephrotic children aged 2-13 years received vaccination against viral hepatitis type B. In 49 children the vaccine was administered during the treatment of the nephrotic syndrome and in the remaining 7 children--after completion of the therapy. Retrospective analysis revealed the presence of infection with hepatitis B virus in 30 (12.8%) nephrotic children. In 20 of those children the presence of infection with hepatitis B virus was detected during the second and succeeding relapses of the syndrome. In 15 (5.1%) children the nephrotic syndrome was probably induced by other infectious diseases and in 7 children the nephrotic syndrome developed as a result of active immunization. Among 56 children who received vaccination against viral hepatitis type B in 6 (10.7%) the increase of urinary protein excretion was observed and 5 developed a succeeding relapse of the syndrome. In 41 of 56 children who received vaccination against viral hepatitis type B the titers of anti-HBs antigen antibodies were measured. The protective titer of anti-HBs antigen antibodies was detected in 39 (95.1%) nephrotic children. It is well known that both active immunization and infectious diseases may induce the nephrotic syndrome. Despite this, vaccination against viral hepatitis type B in nephrotic children is highly recommended, since it influences favorably the further clinical course of the syndrome by the protection of the disease. In our study, none of the nephrotic children who received vaccination developed viral hepatitis type B.

Little is known about the direct impact of immune elements on human colorectal cancer invasiveness and stemness. We investigated the interaction between IL-22+ cells and cancer (stem) cells in colorectal cancer patients. We have demonstrated that Th22-derived IL-22 targets disruptor of telomeric silencing 1-like (DOT1L). DOT1L methylates histone 3 lysine 79 (H3K79) and, in turn, leads to core stem cell gene activation, resulting in increased colon cancer stemness and tumorigenic potential. In addition, increased levels of DOT1L and H3K79me2 in colorectal cancer predict poor patient survival. Collectively, this work identifies that Th22 cells control colon cancer stemness via epigenetic regulation that affects patient outcome. Efforts to target this network might be a strategy in treating patients with colorectal cancer.

Methods allowing control of stereoselectivity in aldol reactions of enolates derived from 1,3-dioxan-5-ones (4) are described. Boron enolates, generated in situ, react with benzaldehyde to give the corresponding anti aldol selectively (the anti:syn ratio of up to 96:4) and in high yield. Lithium enolates give high anti selectivity only with aldehydes branched at the α-position. Enantioselective deprotonation of CS symmetrical dioxanones (e.g., 4b) can be accomplished efficiently, with enantiomeric excess of up to 90%, with chiral lithium amide bases of general structure PhCH(Me)N(Li)R (9, 10) if the R group is sufficiently bulky (e.g, R = adamantyl) or is fluorinated (e.g., R = CH2CF3). Dioxanone boron and lithium enolates react readily with glyceraldehyde derivatives (19), yielding protected ketohexoses (20 and 21).

Methods allowing control of stereoselectivity in aldol reactions of enolates derived from 1,3-dioxan-5-ones (4) are described. Boron enolates, generated in situ, react with benzaldehyde to give the corresponding anti aldol selectively (the anti:syn ratio of up to 96:4) and in high yield. Lithium enolates give high anti selectivity only with aldehydes branched at the alpha-position. Enantioselective deprotonation of C(S) symmetrical dioxanones (e.g., 4b) can be accomplished efficiently, with enantiomeric excess of up to 90%, with chiral lithium amide bases of general structure PhCH(Me)N(Li)R (9, 10) if the R group is sufficiently bulky (e.g, R = adamantyl) or is fluorinated (e.g., R = CH2CF3). Dioxanone boron and lithium enolates react readily with glyceraldehyde derivatives (19), yielding protected ketohexoses (20 and 21).