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PubMed1987

Diagnostic imaging in children with urinary tract infection: review of current concepts and suggested guidelines.

Symptomatic urinary tract infection (UTI) in childhood is estimated to occur with a frequency of up to 3% through adolescence. The practitioner caring for children requires both anatomic and physiologic information concerning the urinary tract to assist in diagnosis, treatment, and prognosis. Advances in diagnostic imaging have resulted in numerous methods for evaluation of the urinary system. These procedures differ in the type of information obtained, risk or discomfort to the patient, and cost. Selection of the proper test(s) requires an understanding of these factors. Based on our survey of recent pertinent literature and our clinical experience, we present guidelines for appropriate diagnostic imaging in children with UTI, and we discuss the benefits and limitations of available imaging techniques along with concepts regarding the pathogenesis of UTI and causes of renal damage from UTI.

Child↗
PubMed2001

Mechanism of the inhibitory effect of protease inhibitor on tumor necrosis factor alpha production of monocytes.

If the inflammatory response becomes excessive or uncontrolled by some stimuli, inappropriate inflammatory responses occur. Monocytes are extremely important cells for regulating the cytokine network and tumor necrosis factor alpha (TNFalpha) and interleukin- (IL) 10, which are mainly synthesized by monocytes, are representative cytokines that play a central role in the cytokine network. Protease inhibitors such as gabexate mesilate (GM) and ulinastatin (UTI) have been shown to have various beneficial effects by inhibiting the activation of leukocytes, but the mechanism for this has yet to be fully elucidated. In this study we investigated the mechanism of the inhibitory effect of protease inhibitors on the proinflammatory cytokine production of lipopolysaccharide- (LPS) stimulated monocytes. LPS-stimulated monocytes were treated with GM or UTI. The value of TNFalpha and IL-10 in the culture medium of monocytes was measured and each mRNA expression was assayed. The inhibitory effect of protease inhibitors on the activity of intracellular signal transduction pathways such as protein kinase C (PKC) and nuclear factor kappa B (NFkappaB) were also evaluated. GM decreased the TNFalpha production of LPS-stimulated monocytes as shown by the inhibition of mRNA expression and increased the IL-10 production of LPS-stimulated monocytes. GM also suppressed the NFkappaB activity of LPS-stimulated monocytes. UTI decreased the TNFalpha production of LPS-stimulated monocytes, but did not inhibit the TNFalpha mRNA expression. The present study shows that the inhibitory effect of GM on the TNFalpha production of activated human monocytes is mediated by the suppression of NFkappaB activation, while the mechanism of UTI inhibiting TNFalpha production of human monocytes may be due to the inhibition of either the translation or secretion of TNFalpha.

Cells, Cultured↗
PubMed2003

Elevated serum procalcitonin values correlate with renal scarring in children with urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) in young children carries the risk of parenchymal damage and sequelae. The location of the infection within the urinary tract influences decisions regarding both therapeutics and follow-up. Because clinical features and laboratory markers of infection at an early age are not specific, it is difficult to make a distinction between lower UTI and acute pyelonephritis. Procalcitonin (PCT) has been studied as a marker of severe bacterial infection. The aim of this study was to test the usefulness of PCT concentration in serum to distinguish between uncomplicated UTI and severe acute pyelonephritis with renal scars. METHODS: PCT was measured by immunoluminometric assay in serum samples from children with microbiologically documented infection. Severe renal involvement was assessed by 99mTc-dimercaptosuccinic acid gammagraphy done 5 to 6 months after the episode to check for the presence of parenchymal scars. C-reactive protein (CRP) and leukocyte count were also measured. RESULTS: PCT at presentation showed a significant correlation (P < 0.001) with the presence of renal scars in children with UTI. Using a cutoff of 1 ng/ml for PCT and 20 mg/l for CRP, sensitivity and specificity in distinguishing between urinary tract infection with and without renal damage were 92.3 and 61.9%, respectively, for PCT and 92.3 and 34.4% for CRP. Positive and negative predictive values were 32 and 97.5%, respectively, for PCT and 23 and 95%, respectively, for CRP. CONCLUSIONS: A low PCT value at admission indicates a low risk of long term renal scarring. Increased PCT values at admission correlate with the presence of scars. PCT values have proved to be more specific than CRP and leukocyte count for identifying patients who might develop renal damage.

Bacterial Infections↗
PubMed2003

Lipopolysaccharide and inflammatory cytokines cause an inducible nitric oxide synthase-dependent bladder smooth muscle fibrotic response.

PURPOSE: Bladder wall fibrosis is a sequela of recurrent urinary tract infection (UTI). Inducible nitric oxide synthase (iNOS) has been shown to mediate the fibrotic response to inflammation in other tissues. We determined if iNOS could be involved in the fibrotic response to recurrent UTI. MATERIALS AND METHODS: Human bladder smooth muscle cells (SMC) were treated with bacterial lipopolysaccharides (LPS) and a mixture of inflammatory cytokines. The level of collagen type III, and the levels of iNOS mRNA, protein and activity were determined. The effect of the iNOS inhibitor aminoguanidine on collagen type III expression was then assessed. RESULTS: Expression of collagen type III, iNOS mRNA and iNOS protein as well as iNOS activity were increased in bladder SMC treated with the combination of LPS and cytokines. The increase in collagen type III expression was inhibited by pretreatment of cells with aminoguanidine. CONCLUSIONS: LPS and inflammatory cytokines induce collagen type III expression in an iNOS dependent manner in human bladder SMC. This finding suggests that iNOS may be a critical mediator of the bladder wall fibrotic response to chronic UTI and iNOS inhibitors may be of therapeutic value in patients with chronic UTI.

Cells, Cultured↗
PubMed2003

Incidence and severity of vesicoureteral reflux in children related to age, gender, race and diagnosis.

PURPOSE: We determine if the incidence and grade of vesicoureteral reflux (VUR) differs in children based on age, race and gender, and if the incidence and severity of VUR are related to race in girls younger than 7 years presenting for evaluation after urinary tract infection (UTI). MATERIALS AND METHODS: The records of all children who underwent a voiding cystourethrogram or radionuclide cystogram between 1993 and 2001 were retrospectively reviewed. Age, gender, race, clinical indication and highest grade of VUR were recorded for the first voiding cystourethrogram or radionuclide cystogram. Frequency tables and logistic regression were conducted to correlate demographics to incidence and severity of VUR. RESULTS: A total of 15,504 patients were included in the analysis. Overall, black children were a third as likely as white children (p <0.0001) and females were twice as likely as males (p <0.0001) to have VUR. Compared to children 0 to 2 years old, the occurrence of reflux was 0.5 times as likely in those 3 to 6 years old (p <0.0001), 0.3 times as likely in those 7 to 11 years old (p <0.0001) and 0.15 times as likely in those 12 to 21 years old (p <0.0001). When analyzing children with UTI, results were similar. Of the patients with VUR 65% were younger than 7 years. The incidence of VUR in black girls younger than 7 years with a diagnosis of UTI was less than 10% compared to white girls, and no black girl had high grade reflux. In young children referred for UTI the incidence and severity of VUR in black patients were significantly lower than those of white girls. CONCLUSIONS: This study validates previous observations regarding the low incidence of VUR in black children.

Age Factors↗
PubMed2004

Spontaneous resolution of high grade infantile vesicoureteral reflux.

PURPOSE: We studied the spontaneous resolution rate in a group of infants with high grade vesicoureteral reflux (VUR). The influence of gender, prenatal or postnatal diagnosis, recurrent urinary tract infections (UTIs) and bladder dysfunction on the resolution rate was also evaluated. MATERIALS AND METHODS: This prospective study comprised 115 infants (80 boys and 35 girls) with high grade VUR (grades III to V). Bilateral reflux was seen in 70% of cases. The majority of patients (71%) were diagnosed after UTI during infancy and only 26% were prenatally diagnosed. Median age at diagnosis was 2.7 months. Patients were followed according to a program of repeat video cystometry and noninvasive 4-hour voiding observations. Median followup was 39 months. RESULTS: The overall spontaneous resolution rate to grade II or less for all grades was 39% with no difference between boys and girls. However, when comparing the more severe grades IV and V, we found a significantly higher resolution rate in boys during the infant year. No difference in VUR disappearance could be detected when comparing the groups according to presentation, prenatal ultrasound or pyelonephritis. Breakthrough UTIs were seen in 47% of cases despite antibacterial prophylaxis and they significantly correlated with VUR nonresolution. Bladder dysfunction was found in 37% of patients and it also significantly correlated with nonresolution. CONCLUSIONS: The spontaneous resolution rate for high grade (grades IV and V) congenital VUR was high in boys during the infant year (29%), whereas in girls and boys after the infant year the resolution rate was 9% yearly during followup. Negative prognostic factors for resolution were recurrent UTIs and bladder dysfunction.

Antibiotic Prophylaxis↗
PubMed2004

Prevalence of diurnal voiding symptoms and difficult arousal from sleep in children with nocturnal enuresis.

PURPOSE: We analyzed the relative contribution of detrusor instability and difficult arousal from sleep in the genesis of nocturnal enuresis (NE), and evaluate a clinical feature that may prospectively help differentiate patients with monosymptomatic NE (mono NE) from those with diurnal voiding symptoms (DVSs) of urgency and urge incontinence associated with NE (NE + DVSs). MATERIALS AND METHODS: Patients referred for voiding problems and 627 controls were evaluated for NE, DVSs, nocturia and arousal from sleep on a scale of 1 to 8. Patients were categorized into 3 groups-mono NE of primary or secondary onset (200, boys 71%, girls 29%), primary or secondary NE + DVSs (329, boys 43%, girls 57%) and isolated DVSs (146, boys 21%, girls 79%). RESULTS: DVSs were noted in 49% of boys and 76% of girls with NE, although 40% of patients or parents did not complain of DVSs. The DVSs were elicited on detailed interrogation or on finding evidence of urinary incontinence on perineal examination. While one-third of controls and patients with isolated DVSs manifested nocturia at least twice a month, only 6% of bedwetters did so. Difficult arousal from sleep (scores 6 to 8) was more prevalent in patients with NE (59%) than controls (20%) or patients with isolated DVSs (5%), and in patients with mono NE and primary NE than in NE + DVSs or secondary NE, with reverse prevalence for nocturia. Easy sleep arousal (scores 1 to 3) was noted in 65% of patients with secondary NE + DVSs vs up to 6% of other NE subgroups. Compared to patients with mono NE, those with NE + DVSs had a higher prevalence of urinary tract infection (UTI), encopresis, psychosocial/learning problems, and family history of UTI and DVSs, ie problems associated with detrusor instability. CONCLUSIONS: DVSs accompany NE in two-thirds of patients but can be missed during a cursory history. Difficult sleep arousal seems to have a major role in primary mono NE, and detrusor instability in secondary NE + DVSs. In patients with NE a history of frequent nocturia, easy sleep arousal, UTI, encopresis, psychosocial learning problems or family history of UTI and DVSs should raise the suspicion for associated undisclosed DVSs.

Adolescent↗
PubMed2005

Escherichia coli strains causing urinary tract infection in uncircumcised infants resemble urosepsis-like adult strains.

PURPOSE: Urinary tract infection (UTI) is the most frequent bacterial infection in infants younger than 90 days, and mainly affects uncircumcised males. In an attempt to unravel further the pathophysiology of UTI in this age group we used molecular methods to characterize Escherichia coli strains responsible for community acquired UTI in male and female infants and in adults. MATERIALS AND METHODS: A total of 79 E. coli isolates from uncircumcised male and female infants with UTI and no urinary tract abnormalities and 41 E. coli pyelonephritis isolates from nonhost compromised adults with bacteremia were characterized in terms of phylogenic relatedness and virulence factors. RESULTS: Males were infected by strains with a genetic background and virulence factors different from those affecting females but similar to those of adult pyelonephritis strains. CONCLUSIONS: Our molecular approach indicates that uncircumcised male infants are at higher risk for infection with highly virulent uropathogenic E. coli strains than are females. Preputial colonization may have a key role in the selection of such strains.

Adult↗
PubMed2005

Urologic diseases in North America Project: trends in resource utilization for urinary tract infections in children.

PURPOSE: We evaluated the health utilization and economic burden on society of urinary tract infections (UTIs) in children using a variety of public and commercial health care databases. MATERIALS AND METHODS: Numerous available databases were evaluated for health care utilization, including inpatient hospitalization, and outpatient physician and emergency department visits, by children with a coded diagnosis of urinary tract infection. Utilization was analyzed by age, gender, race, insurance type and geographic location, and trends were assessed during the last decade. RESULTS: UTIs resulted in more than 1.1 million physician visits annually, accounting for 0.7% of doctor visits and occurring in 2.4% to 2.8% of children. Overall, inpatient hospitalization decreased slightly, although pyelonephritis still accounted for more than 13,000 admissions. Infants were more likely to receive inpatient care for UTIs than children or adolescents, although hospital costs were higher in adolescents. Inpatient hospital costs are estimated to be greater than 180 million dollars per year. CONCLUSIONS: Pediatric UTIs constitute a significant health burden on society. Available data do not allow a full accounting of costs due to a lack of information regarding outpatient expenses, as well as the cost of ancillary evaluation and treatment. However, the magnitude of the burden suggests the importance of further research and data collection of health care utilization in the pediatric population.

Adolescent↗
PubMed2005

Activation of natural killer T cells by alpha-galactosylceramide mediates clearance of bacteria in murine urinary tract infection.

PURPOSE: alpha-Galactosylceramide (alpha-GalCer), which is a specific ligand for CD1d restricted variable-alpha14chain natural killer T cells, has an important role in host defense against a range of microbial infections. We examined whether alpha-GalCer mediates bacterial clearance in a murine urinary tract infection (UTI) model. MATERIALS AND METHODS: The murine UTI model was established by intravesical inoculation of Escherichia coli, Pseudomonas aeruginosa or methicillin resistant Staphylococcus aureus, followed by clamping the distal end of the urethra of C57BL/6 female mice for 4 hours. The antibacterial effect of alpha-GalCer was assessed by comparing the number of cfu/gm kidney tissue 4 days after bacterial inoculation. The prophylactic effect of alpha-GalCer was examined by administrating 3 doses of intraperitoneal alpha-GalCer on alternate days 24 hours before E. coli inoculation. The therapeutic effect of alpha-GalCer was tested by the administration of 2 doses of intraperitoneal alpha-GalCer after bacterial inoculation. To assess cytokine induction by alpha-GalCer serum levels of interleukin-12, interferon-gamma and tumor necrosis factor-alpha were measured by cytometric bead array assay. RESULTS: When administered before bacterial inoculation, alpha-GalCer showed a strong prophylactic antibacterial effect. alpha-GalCer also showed a marked antibacterial effect on preestablished mice UTI caused by E. coli, P. aeruginosa and methicillin resistant S. aureus. alpha-GalCer induced a significantly higher level of interleukin-12, interferon-gamma and tumor necrosis factor-alpha compared with control glycolipids. CONCLUSIONS: These findings suggest a significant role for alpha-GalCer in regulating antibacterial functions by activating natural killer T cells in the murine UTI model.

Animals↗
PubMed2004

Clinical course of urinary tract infections in infants younger than 60 days of age.

OBJECTIVES: Although often managed differently than older children, no study has specifically described the clinical course of urinary tract infections (UTIs) in young infants. Our objective was to determine the risk of progression of illness and the pattern of fever resolution in infants younger than 60 days of age with Gram-negative rod UTIs. METHODS: We completed a retrospective medical chart review. Patients younger than 60 days of age presenting to an urban, tertiary care pediatric hospital were included if they had single organism growth of Gram-negative rods in any amount from suprapubic aspiration samples or more than 10,000 cfu/mL from catheterized specimens. Significant progression of illness was defined as the need for transfer to an intensive care setting. Fever was defined as a rectal temperature of 38.0 degrees C or higher or an axillary temperature 37.0 degrees C or higher. Temperatures were assigned to blocks of 4 hours. RESULTS: Of 128 patients with available records, none were transferred from the general pediatric ward to the intensive care unit and 2 were transferred to a step-down unit for events potentially unrelated to the UTI. No patient had a positive repeat urine culture. For patients with fever, median time to fever resolution was within the 4 to 8 hour time block. Eighty-five percent of the febrile patients became afebrile within 24 hours and only 3.6% were febrile after 48 hours. CONCLUSIONS: Progression of illness in infants with Gram-negative rod UTIs is unlikely. Fever resolution is rapid. If subsequent studies concur with our findings, outpatient therapy or short-stay unit admission may become a viable management strategy.

Anti-Bacterial Agents↗
PubMed2004

Urolithiasis after kidney transplantation in pediatric recipients: a single center report.

BACKGROUND: Urolithiasis occurs in approximately 6% of adult kidney transplant (KTx) recipients. Limited data are available on urolithiasis after pediatric KTx. We report the incidence, management of, and risk factors for stone development in children after KTx. METHODS: We reviewed the medical records of 399 children who received KTx at our center between September 1986 and January 2003. Transplant outcomes were compared in stone formers and controls. RESULTS: Twenty (5%) patients, age 9+/-5 (X +/- SD) years, developed stones over the follow-up period (74+/-53 months). Time to stone presentation was 19+/-22 months post-KTx. Presenting features were urinary tract infection (UTI), 8; gross hematuria, 5; microscopic hematuria, 2; dysuria without infection, 6; difficulty voiding, 3; and silent stones, 2. Stones were removed by cystoscopy in 11 (55%) patients. Stone composition was determined in 11 patients: calcium phosphate (55%), calcium oxalate (18%), mixed calcium phosphate and oxalate (9%), and struvite (18%). Factors predisposing to stones in study patients included suture retention (n = 4), elevated urinary calcium excretion (n = 2), recurrent UTI (n = 2), and urinary stasis (n = 2). The incidence of UTI was higher (P = 0.003) and of acute rejection was lower (P = 0.02) in stone patients compared with controls. Patient and graft survival rates and the incidence of chronic rejection did not significantly differ between study patients and controls (P = NS). CONCLUSIONS: Urolithiasis is not uncommon in pediatric KTx patients. Factors associated with post-KTx urolithiasis include retention of suture material, recurrent UTI, hypercalciuria, and urinary stasis. Treatment is associated with excellent outcome and low recurrence rate.

Adolescent↗
PubMed2006

Urine cytokines profile in renal transplant patients with asymptomatic bacteriuria.

BACKGROUND: The role of asymptomatic bacteriuria in kidney transplant recipients is unknown. There is no clear evidence of its effect on transplanted kidney. METHODS: We studied urine cytokines profile among kidney transplant recipients with bacteriuria found in screening examination. Urine cultures were collected in 269 patients with stable graft function and serum creatinine level <2 mg/dl, during their routine visits. Interleukin (IL)-6 and IL-8 levels were measured in urine samples from patients with asymptomatic bacteriuria, symptomatic urinary tract infection and patients without bacteriuria (control group). Changes in serum creatinine level in patients with asymptomatic bacteriuria and in the control group were observed during 12 months follow up. RESULTS: Urinary tract infection (UTI) was diagnosed in five patients and asymptomatic bacteriuria in 22 patients. Urine IL-6 level was significantly higher in symptomatic UTI group (median 15.71 pg/mg) but there were no differences between group of patients with asymptomatic bacteriuria (3.92 pg/mg) and control group (2.54 pg/mg). Urine IL-8 level was higher in symptomatic UTI group (median 146.8 pg/mg) and was also significantly higher in asymptomatic bacteriuria group (33.49 pg/mg) in comparison to control group (2.97 pg/mg; P=0.0002). During 1-year follow up, incidence of UTI was higher in the asymptomatic bacteriuria group than in the control group but graft function was not different in both groups. CONCLUSIONS: Elevated urine IL-8 level in kidney transplant patients with asymptomatic bacteriuria may reflect impaired immune response to bacterial infection and occult inflammatory process in urinary tract.

Adult↗
PubMed2004

Underdiagnosis of urinary tract infection caused by Methylobacterium species with current standard processing of urine culture and its clinical implications.

Methylobacterium species are environmental opportunistic bacteria, and urinary tract infection (UTI) caused by these pathogens has not yet been documented. Four cases of UTI with Methylobacterium bacteraemia in immunocompetent female patients are reported. Their urine cultures, processed according to standard procedures (i.e. incubation at 35 degrees C in ambient air for 24 h before incubation at room temperature for a further 24 h), were either negative or positive for Escherichia coli. Specially designed experiments indicated that colonies of Methylobacterium species were visualized on blood agar only after incubation at 35 degrees C for at least 40 h, and growth was completely suppressed when concurrently incubated with much smaller inocula of E. coli. The isolates were variably susceptible to cephalosporins, but 100 % susceptible to aminoglycosides. This study suggests an underdiagnosis of UTI caused by Methylobacterium species when the standard procedure of processing urine cultures is used, and implies that administration of aminoglycosides is important when treatment of UTIs with cephalosporin fails.

Adult↗
PubMed2005

Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infection.

Urinary tract infection (UTI) is the most common nonepidemic bacterial infection in humans, representing a constant danger for the host. Both innate and adaptive components of the immune system as well as stromal cells including bladder epithelium are involved in the prevention and clearance of UTI. However, the particular properties of the urogenital tract, which does not comprise typical physical barriers like a mucus or ciliated epithelium, necessitate soluble mediators with potent immunomodulatory capabilities. One candidate molecule capable of both mediating direct antimicrobial activity and alerting immune cells is the evolutionary conserved Tamm-Horsfall protein (THP). Tamm-Horsfall protein is exclusively produced by the kidney in the distal loop of Henle; however, its definite physiological function remains elusive. Mounting evidence indicates that beyond a mere direct antimicrobial activity, THP exerts potent immunoregulatory activity. Furthermore, the genetic ablation of the THP gene leads to severe infection and lethal pyelonephritis in an experimental model of UTI. Recent data are provided demonstrating that THP links the innate immune response with specific THP-directed cell-mediated immunity. In light of these novel findings we discuss the particular role of THP as a specialized defence molecule. We propose an integrated model of protective mechanisms against UTI where THP acts by two principle nonmutually exclusive mechanisms involving the capture of potentially dangerous microbes and the ability of this peculiar glycoprotein to induce robust protective immune responses against uropathogenic bacteria.

Anti-Infective Agents↗
PubMed1989

Bacteriuria and urinary incontinence in aged female nursing home residents.

Although urinary incontinence (UI) is identified as a symptom of urinary tract infection (UTI), the incontinent elderly frequently are not treated for UTI unless clinically significant manifestations are present. The purpose of this research was to identify variables that may be associated with bacteriuria in the female person who is already known to be incontinent. A sample of 65 incontinent female nursing home residents was divided into three groups: (1) those with negative urine screens; (2) those with a bacterial count of over 100,000 per ml of urine; and (3) those with a bacterial count of below 100,000 per ml urine. Variables examined were: (1) physical symptoms; (2) physical examination findings; (3) mental status; and (4) functional abilities. Significant group differences were found regarding awareness of the urge to void and ability to hold urine. A near significance finding suggested that the higher the level of cognitive function the less likely the presence of UTI. There was some evidence to suggest the higher the level of independence the less likely the presence of UTI. Recommendations for nursing practice and future nursing research are made.

Activities of Daily Living↗
PubMed2004

Longer than recommended empiric antibiotic treatment of urinary tract infection in women: an avoidable waste of money.

CONTEXT: Current Israeli guidelines for the empiric treatment of uncomplicated urinary tract infection (UTI) in women recommend nitrofurantoin for 5 days. Some physicians nevertheless opt for ofloxacin, which should be prescribed for 3 days according to universally accepted guidelines. OBJECTIVE: To evaluate the economic consequences of longer than recommended durations of antibiotic therapy in the empiric treatment of uncomplicated UTI in women. DESIGN, SETTING AND PATIENTS: Data were derived from the electronic records of one of the four health maintenance organizations in Israel. The sample included all women aged 18-75 years who were diagnosed with acute cystitis or UTI from January 2001 to June 2002 and were empirically treated with antibiotics. Of the 7738 patients identified, 1138 received nitrofurantoin and 1054 ofloxacin. The excess expenditure accrued due to longer than recommended therapy with these drugs was evaluated. RESULTS: The rate of adherence was 22.23% for nitrofurantoin (95% CI=19.81%, 24.65%), and 4.08% for ofloxacin (95% CI=2.88%, 5.28%). The average excess expenditure per case was 5.78 USD (US Dollar) with ofloxacin and 3.43 USD with nitrofurantoin, resulting in an annual loss to the health maintenance organizations of approximately 19,000 USD. When extrapolated to the national population of 6.5 million, the loss due to inappropriate treatment of adult women is 190,000 USD. CONCLUSIONS: The lack of adherence to national and international guidelines with regard to the recommended duration of antibiotic treatment of UTI in women resulted in a significant and avoidable waste of health system resources. This study suggests that drug utilization analyses that concentrate solely on the choice of drug may be overlooking important information.

Adolescent↗
PubMed1995

The uniform galactose 4-sulfate structure in the carbohydrate-protein linkage region of human urinary trypsin inhibitor.

The carbohydrate-protein linkage region of a chondroitin 4-sulfate chain attached to urinary trypsin inhibitor (UTI) was isolated from human urine and characterized structurally. The chondroitin 4-sulfate chain was released from UTI by beta-elimination using alkaline NaBH4 then digested with chondroitinase ABC. These treatments resulted in only a single hexasaccharide alditol derived from the carbohydrate-protein linkage region. Chemical and enzymic analyses and 600-MHz 1H-NMR spectroscopy revealed that the hexasaccharide alditol had the following structure: delta HexA alpha 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1- 3Gal(4-sulfate) beta 1-3Gal beta 1-4Xyl-ol, where delta HexA, GlcA and Xyl-ol represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid, D-glucuronic acid and D-xylitol, respectively. This structure contained the novel 4-sulfated Gal residue, which was first demonstrated in one of the three linkage hexasaccharide-serines isolated from chondroitin 4-sulfate of rat chondrosarcoma [Sugahara, K., Yamashina, I., de Waard, P., Van Halbeek, H. & Vliegenhart, J. F. G. (1988) J. Biol. Chem. 263, 10168-10174]. This disulfated structure was recently identified as the sole structural component in the linkage hexasaccharide alditol fraction isolated from inter-alpha-trypsin inhibitor (ITI) in human plasma [Yamada, S., Oyama, M., Kinugasa, H., Nakagawa, T., Kawasaki, T., Nagasawa, S., Khoo, K.-H., Morris, H.R., Dell, A. & Sugahara, K. (1995) Glycobiology 5, 335-341]. The structural uniformity in the linkage hexasaccharide structure of ITI and UTI is in marked contrast to the heterogeneity demonstrated in the linkage hexasaccharides isolated from cartilaginous chondroitin sulfate whose linkage regions are sometimes but not always phosphorylated on the Xyl residue or sulfated on the Gal residue(s). The uniform structure containing the novel 4-sulfated Gal residue in the linkage region of UTI and ITI may imply its significance in the biosynthetic mechanism of chondroitin sulfate.

Animals↗