Biomedical subjects

S Ono

Publications and source records attributed to S Ono.

At least 181 records · Page 10Linked to original sources

PubMed1999

Effects of a protease inhibitor on reduction of surgical stress in esophagectomy.

OBJECTIVE: To evaluate the efficacy of gabexate mesilate (GM) in reducing surgical stress after esophagectomy. METHODS: In a prospective, randomized, clinical study, 11 patients with squamous cell carcinoma of the esophagus were randomly assigned to two groups: 5 patients were continuously administered gabexate mesilate 1.5 mg/kg per hour from the beginning of anesthesia until the third postoperative day (preop GM group); and 6 patients were administered gabexate mesilate 1.5 mg/kg per hour continuously from the end of surgery and for the same postoperative period (postop GM group). Blood samples were taken from all patients before surgery, immediately after it, and 3 days after surgery. Serum interleukin-6 (IL-6) level, tumor necrosis factor-alpha (TNF-alpha) production, and Mac-1 antigen expression of peripheral blood monocytes were measured. Clinical courses of patients in the two groups were compared. RESULTS: Time courses of serum IL-6 levels in the preop GM group were significantly lower than those in the postop GM group. Ex vivo TNF-alpha production by lipopolysaccharide (LPS) stimulated monocyte was much higher than that by monocyte without LPS stimulation. Gabexate mesilate showed a little inhibition of TNF-alpha production by monocyte without LPS stimulation. On the other hand, gabexate mesilate significantly inhibited TNF-alpha production by LPS stimulated monocyte. Mac-1 antigen expression by monocyte immediately after operation in the preop GM group was significantly lower than that in the postop GM group. Duration of systemic inflammatory response syndrome was significantly shorter in the preop GM group than in the postop GM group. CONCLUSIONS: Reduction of systemic inflammatory response syndrome duration after esophagectomy by the continuous administration of gabexate mesilate started before operation may be through the suppression of TNF-alpha production capacity and Mac-1 expression on monocytes immediately after operation, and to suppression of increase in serum IL-6 level.

Aged↗

PubMed1999

Cellular activity in the gallbladder of children with anomalous arrangement of the pancreaticobiliary duct.

BACKGROUND/PURPOSE: Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is closely related to congenital biliary dilatation and frequently associated with biliary tract malignancy. To examine the mechanism of biliary tract carcinogenesis in patients with AAPBD, we investigated histologically the early changes in cell proliferative kinetics of the gallbladder mucosa of children with AAPBD. METHODS: Twenty-three specimens of gallbladder were obtained from 23 children with AAPBD, and six control specimens were obtained from pediatric patients. All specimens were fixed routinely and paraffin embedded and examined histologically with H&E staining and immunohistochemically with monoclonal antibody Ki-67(MIB-1), which reacts with a human nuclear antigen associated with cell proliferation. Ki-67 labeling index (Ki-67 LI) was obtained by counting the numbers of Ki-67-positive cells per 1,000 gallbladder epithelial cells. RESULTS: Significant differences in Ki-67 LI were noted between children with and without AAPBD. Furthermore, Ki-67 LI and the incidence of epithelial hyperplasia of gallbladder were significantly higher in children with AAPBD in whom the major pancreatic duct joined the common bile duct (P-C type) than in those in whom the common bile duct joined the major pancreatic duct (C-P type). CONCLUSIONS: Cellular proliferative activity was increased in children with AAPBD, especially those with the P-C-type anomaly. These results suggest that the early mucosal changes of the gallbladder occurred in early childhood of patients with AAPBD and might be associated with gallbladder cancer. Early diagnosis and early surgical division of the biliary tract and pancreatic duct is recommended for children with AAPBD.

Adolescent↗

PubMed1999

Effects of T-588, a novel cognitive enhancer, on ADP-ribosylation of G(s alpha) by cholera toxin and cyclic AMP accumulation in rat cerebral cortex.

We investigated the effects of R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy]ethan ol hydrochloride (T-588), a novel cognitive enhancer, on trimeric GTP-binding proteins (G proteins) and cyclic AMP accumulation in rat cerebral cortex. T-588 (0.1-1.0 mM) inhibited the ADP-ribosylation of alpha subunit of Gs in a concentration-dependent manner. Auto-ADP-ribosylation of CTX was not inhibited by T-588. The stimulatory effect of guanosine 5'-(3-O-thio)triphosphate (GTPgammaS) on CTX-catalyzed ADP-ribosylation was attenuated by adding T-588 in assay mixture. ADP-ribosylation of Gi/Go by pertussis toxin was slightly inhibited by T-588. Isoproterenol-stimulated cyclic AMP accumulation was inhibited by adding 3 mM T-588 to rat cerebral cortical slices. Next, we investigated the effects of isoproterenol and T-588 on GTPgammaS binding. Membranes were first incubated with or without isoproterenol and T-588 in the presence of 0.2mM GTPgammaS, then cholate extract preparations were prepared from the washed membranes. Interestingly, the [32P]ADP-ribosylation of G(s alpha) was enhanced not only by isoproterenol but also by T-588. Although the obtained results are apparently inconsistent, T-588 seems to interact with G proteins, specifically Gs.

Adenosine Diphosphate Ribose↗

PubMed1999

Putting a new twist on actin: ADF/cofilins modulate actin dynamics.

The actin-depolymerizing factor (ADF)/cofilins are a family of essential actin regulatory proteins, ubiquitous among eukaryotes, that enhance the turnover of actin by regulating the rate constants of polymerization and depolymerization at filament ends, changing the twist of the filament and severing actin filaments. Genetic and cell-biological studies have shown that an ADF/cofilin is required to drive the high turnover of the actin cytoskeleton observed in vivo. The activity of ADF/cofilin is regulated by a variety of mechanisms, including specific phosphorylation and dephosphorylation. This review addresses aspects of ADF/cofilin structure, dynamics, regulation and function.

3T3 Cells↗

PubMed1999

Application of surface-coated liposomes for oral delivery of peptide: effects of coating the liposome's surface on the GI transit of insulin.

We prepared two kinds of surface-coated liposomes and investigated their potencies as oral dosage forms for peptide drugs by focusing on their effects on the gastrointestinal (GI) transit of drugs. The surface of the liposomes was coated with poly(ethylene glycol) 2000 (PEG-Lip) or the sugar chain of mucin (Mucin-Lip). As a model peptide drug, insulin was encapsulated in these liposomes. Coating the surface with poly(ethylene glycol) was found to reduce the transit rate of liposomes in the small intestine after oral administration to rats in vivo. Mucin-Lip was retained in the stomach longer than PEG-Lip or uncoated liposomes. The effect of surface coating on the intestinal transit of liposomes was determined by means of in situ single pass perfusion in the rat small intestine. Statistical moment analysis was applied to the outflow pattern of both liposomes and encapsulated insulin. The mean transit time (MTT) and deviation of transit time (DTT) in the intestinal tract were calculated. The MTT of PEG-Lip was much longer than those of uncoated liposomes and Mucin-Lip and was significantly shortened after removal of the intestinal mucous layer. These results indicated that PEG-Lip interacts strongly with the intestinal mucous layer, leading to its slow transit in the intestine. In contrast, coating the liposome's surface with mucin did not affect either the MTT or DTT of liposomes in the intestine. This result is in accordance with the in vivo observation that Mucin-Lip was highly retained in the stomach, but not in any region of the small intestine in vivo. Both the MTT and DTT values of insulin encapsulated in PEG-Lip and Mucin-Lip were almost the same as those of liposomes themselves, suggesting that surface-coated liposomes retained insulin in the intestinal tract. However, MTT and DTT of insulin were significantly shorter than those of uncoated liposomes because these liposomes degraded and released significant amounts of insulin during single pass perfusion. The ability of surface-coated liposomes, especially of PEG-Lip, to interact with the mucus layer and slow the transit rate in the GI tract is considered desirable for oral delivery of peptide drugs. Modification of the liposomal surface with appropriate materials, therefore, should be an effective method by which to achieve the oral delivery of peptide drugs.

Animals↗

PubMed1999

Serum levels of soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-2 receptor in patients with vernal keratoconjunctivitis and allergic conjunctivitis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is characterized by severe ocular allergic inflammation that may have a poor visual prognosis. Due to the high frequency of the presence of atopic dermatitis (AD) in VKC, most systemic parameters are dependent on the clinical severity of AD. METHODS: Serum levels of sICAM-1, sVCAM-1, and sIL-2R were measured by enzyme-linked immunoassay using samples from 30 VKC patients, 30 allergic conjunctivitis (AC) patients, and 20 normal subjects, to determine whether the concentrations of these molecules are elevated. RESULTS: Circulating sICAM-1 and sIL-2R levels were increased in patients with VKC with AD compared with those in VKC without AD, AC, and normal controls. Serum levels of sVCAM-1 in VKC patients with and without AD were significantly higher than those in controls. No significant difference was found in the levels of sVCAM-1 between patients with VKC with and without AD. In VKC patients with AD, the sIL-2R level correlated significantly with severity of AD, whereas no such correlation was found for sICAM-1 and sVCAM-1. CONCLUSIONS: These results suggest that serum sVCAM-1 can be used as a marker to differentiate VKC from nonproliferative ocular allergic diseases, and specific immunologic features of VKC may underlie the upregulation of serum sVCAM-1.

Adolescent↗

PubMed1999

Bilateral pneumothoraces with multiple bullae in a patient with asymptomatic bronchiolitis obliterans 10 years after bone marrow transplantation.

A 16-year-old boy developed bronchiolitis obliterans (BO) 10 years after BMT for myelodysplastic syndrome. Although the patient complained of almost no dyspnea on exertion, he had mild hypercapnea with a markedly reduced forced expiratory volume of 0.32 l. Chest X-rays showed occasional bilateral minimal pneumothoraces, which is in accordance with the existence of multiple small bullae found on the pleural surface at video-assisted thoracic surgery. Histologic examination of the biopsied lung revealed BO. This case indicates that BO in adolescence following BMT and possible chronic GVHD may be masked because of lung immaturity at BMT, and BO after BMT may be associated with multiple pleural bullae.

Adolescent↗

PubMed1999

5'-upstream structure of the gene coding for chicken riboflavin-binding protein and its relation to estrogen induction.

To elucidate the mechanism of the estrogen-dependent induction of chicken riboflavin-binding protein (RfBP), we analyzed the 5'-upstream structure of its gene. A noncoding exon exists there, and around this sequence, 9 widely spaced half-palindromic estrogen-response element (ERE) motifs (5'-GGTCA or 5'-TGACC) were found. Furthermore, an imperfect ERE-like palindromic sequence (5'-ATGTCANNNTGACAT-3') was also found at the 2.25 kb upstream region. No consensus palindromic ERE was observed. By luciferase reporter assay, the regions containing the half ERE motifs and the imperfect ERE showed estrogen-dependent enhancer activities, suggesting that these two characteristic sequences might confer estrogen-inducibility upon the chicken RfBP gene. However the activities were lower than that of a consensus ERE. It remains uncertain whether these sequences act cooperatively.

5' Untranslated Regions↗

PubMed1999

Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric oxide and cyclic guanosine monophosphate production in cultured rat vascular smooth-muscle cells.

BACKGROUND: Recently rat vascular smooth-muscle cells (VSMC) have been shown to possess Epo receptor, and respond to various cytokines for producing nitric oxide (NO). In the present study we examined the effect of pharmacological dose of human recombinant erythropoietin (rHuEpo) on the IL-1beta-induced NO and cGMP production as well as inducible nitric oxide synthase (iNOS) in cultured rat VSMC. METHODS: Nitrite, a stable metabolite of NO, and intracellular cGMP contents were assayed by Griess method and enzyme immunoassay. iNOS mRNA expression was analysed by Northern blotting. RESULTS: RHuEpo inhibited IL-1beta-induced nitrite production in a dose- and time-dependent manner with concomitant changes of intracellular cGMP contents. On the other hand, rHuEpo did not inhibit atrial natriuretic peptide- (ANP) or sodium nitroprusside (SNP)-induced nitrite and cGMP production at all. While rHuEpo inhibited IL-1beta-induced iNOS mRNA expression, rHuEpo vehicle did not affect IL-1beta-induced iNOS mRNA expression. CONCLUSIONS: It is suggested that a pharmacological dose of rHuEpo inhibits IL-1beta-induced NO and cGMP production as well as iNOS mRNA expression, presumably via the Epo receptor.

Animals↗

PubMed1999

The effect of erythropoietin on interleukin-1beta mediated increase in nitric oxide synthesis in vascular smooth muscle cells.

OBJECTIVE: Recently, we observed that recombinant human erythropoietin (rHuEPO) inhibits the interleukin (IL)-1beta induced nitric oxide (NO) production and inducible NO synthase (iNOS) expression in cultured rat vascular smooth muscle cells (VSMC). The mechanisms of these inhibitory effects of rHuEPO were evaluated. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was performed to identify a specific erythropoietin receptor (EpoR). Tyrosine phosphorylation of phospholipase C (PLC) was analyzed by combination of immunoprecipitation and Western blotting. Protein kinase C (PKC) activities were analyzed by phosphorylation assay of myelin basic protein (MBP4-14). VSMC were incubated with test agents for 24 h and nitrite as a stable NO metabolite was measured. iNOS mRNA and protein expression was analyzed by Northern and Western blotting, respectively. RESULTS: RT-PCR analysis revealed that EpoR m-RNA was expressed; furthermore, it might be alternatively spliced in VSMC. rHuEPO induced tyrosine phosphorylation of PLC-gamma1 and activation of PKC. rHuEPO inhibited not only IL-1beta induced nitrite production, but also the expression of iNOS mRNA and protein. These inhibitory effects of rHuEPO were reversed in the presence of PKC inhibitors, calphostin C (1 pmol/l) or staurosporine (10 nmol/l). PKC activation by phorbol myristate acetate inhibited nitrite production. The inhibitory effect of rHuEPO on IL-1beta induced nitrite production was also eliminated in PKC depleted cells or in the existence of anti-EpoR antibody. CONCLUSION: rHuEPO inhibits IL-1beta induced NO production by suppressing iNOS mRNA and protein expressions through EpoR, and the PLC-gamma1 and PKC pathway may be involved.

Animals↗

PubMed1999

Detection of CBF deficits in neuropsychiatric disorders by an expert system: a 99Tcm-HMPAO brain SPET study using automated image registration.

The aims of this study were to develop an objective method for assessing rCBF deficits using a statistical image analysis protocol and to validate its effective use in clinical practice. 99Tcm-HMPAO brain SPET images were acquired for 40 normal subjects, 10 patients with Alzheimer's disease and 10 patients with depression. Automated image registration was used to standardize the size and shape of the brain structures for all subjects. The images of the first 30 normal subjects were used to construct a normal database. The CBF images of the other 10 normal subjects and the 20 patients were compared voxel by voxel with the normal database to map CBF abnormalities by statistical evaluation. The results were compared with the clinical reports of CBF images. The expert system detected all rCBF deficits reported by the nuclear physicians. Some additional areas with special information, like atrophy and bilateral asymmetry, were also identified by the expert system. We conclude that this expert system can delineate CBF deficits with sufficiently high accuracy, differentiating normal from abnormal CBF images using voxel-based comparisons. The use of an expert system improves rCBF SPET image evaluation.

Aged↗

PubMed1999

Decreased urinary concentrations of type IV collagen in amyotrophic lateral sclerosis.

OBJECTIVES: Type IV collagen (IV-C) abnormalities of skin and serum have been reported in patients with amyotrophic lateral sclerosis (ALS). However, there has been no study of urinary IV-C in ALS. The present study investigates urinary IV-C and the relation to its skin content in patients with ALS. MATERIAL AND METHODS: We studied IV-C immunoreactivity of skin and measured urinary levels of IV-C in ALS patients and controls. RESULTS: The basement membrane as well as blood vessels of skin in ALS patients was weakly positive for IV-C as compared with those of controls. Immunostaining became even weaker as ALS progressed. The urinary level of IV-C in ALS patients was significantly decreased as compared to diseased controls (P<0.001) and healthy controls (P<0.001), and was negatively and significantly associated with duration of symptoms (r=-0.85, P<0.001). There was an appreciable positive correlation between urinary IV-C levels and the density for IV-C immunoreactivity in ALS patients (r=0.84, P<0.01). CONCLUSION: These data suggest that a metabolic alteration of IV-C may occur in ALS patients and decreased levels of urinary IV-C may be related to the decreased IV-C immunoreactivity of skin in ALS.

Aged↗

PubMed1999

Increased type III procollagen in serum and skin of patients with amyotrophic lateral sclerosis.

OBJECTIVES: Collagen abnormalities of skin have been reported in patients with amyotrophic lateral sclerosis (ALS). However, little is known concerning the aminoterminal propeptide of type III procollagen (PIIIP) and type III collagen in ALS. The aim of this study is to measure PIIIP, a precursor form of type III collagen, in skin and serum of ALS. MATERIAL AND METHODS: We studied PIIIP immunoreactivity of skin and measured serum levels of PIIIP in ALS patients, and the results were compared with those of control subjects. RESULTS: Collagen bundles in the dermis of ALS were immunohistochemically strongly positive for PIIIP as compared with those of controls. The optical density of PIIIP immunostaining reactivity in ALS patients was significantly higher than in controls, and was significantly increased with duration of illness. Serum PIIIP levels in patients with ALS were significantly increased as compared with those in diseased control subjects and those in healthy control ones, and were positively and significantly associated with duration of illness. There was an appreciable positive correlation between concentrations of serum PIIIP and the density of PIIIP immunoreactivity of skin in ALS patients. CONCLUSION: These data suggest that a metabolic alteration of PIIIP may take place in the skin of ALS and the increased levels of serum PIIIP may reflect the increased PIIIP immunoreactivity of skin in ALS.

Activities of Daily Living↗

PubMed1999

Tc-99m HMPAO SPECT in the evaluation of Alzheimer's disease: correlation between neuropsychiatric evaluation and CBF images.

The purpose of this study was to evaluate the effects of various covariants on the distribution pattern of Tc-99m HMPAO in patients with Alzheimer's disease by correlation analysis. Twenty patients with Alzheimer's disease and 15 age matched normal subjects participated. Tc-99m HMPAO brain SPECT and x ray computed tomography (CT) were acquired for each subject. SPECT images were transformed to a standard size and shape by automated image registration (AIR) and were used for group comparison by means of SPM96. Voxel based covariance analysis was performed on standardised images taking the age of patients, severity of disease (clinical dementia rating scale, mini mental state examination, physical self maintenance scale), and atrophy indices as variables. There was significantly decreased regional cerebral blood flow (rCBF) in the frontal, parietal, and temporal regions in the patient group (p<0.001), more marked in those patients having severe dementia. Covariance analysis disclosed that aging and severity of disease have a pronounced effect on rCBF, especially that of the left parietal region.

Aged↗

PubMed1999

AVP inhibits LPS- and IL-1beta-stimulated NO and cGMP via V1 receptor in cultured rat mesangial cells.

The present study examined how arginine vasopressin (AVP) affects nitric oxide (NO) metabolism in cultured rat glomerular mesangial cells (GMC). GMC were incubated with test agents and nitrite, and intracellular cGMP content, inducible nitric oxide synthase (iNOS) mRNA, and iNOS protein were analyzed by the Griess method, enzyme immunoassay, and Northern and Western blotting, respectively. AVP inhibited lipopolysaccharide (LPS)- and interleukin-1beta (IL-1beta)-induced nitrite production in a dose- and time-dependent manner, with concomitant changes in cGMP content, iNOS mRNA, and iNOS protein. This inhibition by AVP was reversed by V1- but not by oxytocin-receptor antagonist. Inhibition by AVP was also reproduced on LPS and interferon-gamma (IFN-gamma). Protein kinase C (PKC) inhibitors reversed AVP inhibition, whereas PKC activator inhibited nitrite production. Although dexamethasone and pyrrolidinedithiocarbamate (PDTC), inhibitors of nuclear factor-kappaB, inhibited nitrite production, further inhibition by AVP was not observed. AVP did not show further inhibition of nitrite production with actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of protein synthesis. In conclusion, AVP inhibits LPS- and IL-1beta-induced NO production through a V1 receptor. The inhibitory action of AVP involves both the activation of PKC and the transcription of iNOS mRNA in cultured rat GMC.

Animals↗

PubMed1999

Impairment of transalveolar fluid transport and lung Na(+)-K(+)-ATPase function by hypoxia in rats.

We examined whether hypoxic exposure in vivo would influence transalveolar fluid transport in rats. We found a significant decrease in alveolar fluid clearance of the rats exposed to 10% oxygen for 48 h. Terbutaline did not stimulate alveolar fluid clearance, and alveolar fluid cAMP levels were lower than those determined in normoxia experiment. Hypoxia did not influence the alveolar fluid lactate dehydrogenase levels, Evans blue dye fluid-to-serum concentration ratio, or lung wet-to-dry weight ratio, indicating no significant change in the permeability of alveolar-capillary barrier. Histological examination showed no significant fluid accumulation into the interstitium and the alveolar space. Hypoxia did not reduce lung ATP content; however, we found significant decrease in Na(+)-K(+)-ATPase hydrolytic activity in lung tissue preparations and isolated alveolar type II cells. Our data indicate that hypoxic exposure in vivo impairs transalveolar fluid transport, and this impairment is related to the decrease in alveolar epithelial Na(+)-K(+)-ATPase hydrolytic activity but is not secondary to the alteration of cellular energy source.

Adenosine Triphosphate↗

PubMed1999

Decrease in the ciliary neurotrophic factor of the spinal cord in amyotrophic lateral sclerosis.

Ciliary neurotrophic factor (CNTF), a potent survival factor in spinal motoneurons of embryonic chick and rat, is currently being investigated in humans as a treatment for amyotrophic lateral sclerosis (ALS). However, its physiological and pathological activities in ALS remain unclear. We measured CNTF contents in the cervical enlargement of the spinal cord from 9 ALS patients and 12 age-matched control subjects using a sensitive enzyme-linked immunoassay. CNTF genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. In control subjects, there were 8 homozygotes and 4 heterozygotes, while in ALS patients there were 6 and 3, respectively. In both homozygotes and heterozygotes, CNTF expression in the spinal cord from ALS patients tended to decrease compared to control subjects. In homozygotes, the decrease was significant (p < 0.05). Concerning the regional concentrations of CNTF, in homozygotes, CNTF contents in the lateral corticospinal tract were markedly lower (p < 0.001) in ALS patients than in controls. The decrease in CNTF expression in the lateral corticospinal tract of the spinal cord from ALS patients may be a feature of ALS and could be related to motor neuron loss.

Amyotrophic Lateral Sclerosis↗

PubMed1999

No effect of gender or age on binding characteristics of valproic acid to serum proteins in pediatric patients with epilepsy.

The gender- and age-related binding characteristics of valproic acid to serum proteins were determined in the pediatric population. Serum samples examined in the study were obtained from 61 pediatric patients (28 males, 33 females) with epilepsy on valproic acid monotherapy. Their ages ranged from 1 to 15 years (mean age with [SD]: 7.8 [3.9] years; < 10 years, n = 41; > or = 10 years, n = 20). The in vivo population binding parameters of valproic acid to serum proteins and theoretical minimal unbound serum fraction (fu) of valproic acid were determined in (1) all, (2) male and female subgroups, and (3) prepubescent (< 10 years) and pubescent (> or = 10 years) subgroups. The association constant (K) was approximately 1.4 times higher in male (0.018 L/mumol) than in female (0.013 L/mumol) patients, while the total concentration of binding sites (n(Pt)) was 1.2 times greater in female (1235 mumol/L) than in male (997 mumol/L) patients. The fu was 0.053 and 0.059 for male and female patients, respectively. The value of K was approximately 1.6 times higher in the pubescent (0.019 L/mumol) than in the prepubescent (0.012 L/mumol) patients, while the n(Pt) was 1.2 times higher in the prepubescent (1244 mumol/L) than in the pubescent (1057 mumol/L) patients. The fu was 0.063 for the prepubescent and 0.047 for the pubescent patients. No significant differences were observed in binding characteristics of valproic acid to serum proteins between male and female or younger and older patients. However, the differences in valproic acid binding to serum proteins appear to be relatively larger in binding affinity than in binding capacity between the two groups. Because no significant differences were observed in serum concentrations of total and unbound valproic acid, albumin, or free fatty acids between any subgroups (male and female, younger and older), the results suggest that gender or age may not be factors for the determination of the binding characteristics of valproic acid to serum proteins in pediatric patients.

Adolescent↗