Thermodynamic characterization of interactions of native bovine serum albumin with highly excluded (glycine betaine) and moderately accumulated (urea) solutes by a novel application of vapor pressure osmometry

The thermodynamic consequences of interactions of native bovine serum albumin (BSA) with two smaller solutes (glycine betaine or urea) in aqueous solution are characterized by a novel application of vapor pressure osmometry (VPO), which demonstrates the utility of this method of investigating preferential interactions involving solutes that are either accumulated or excluded near the surface of a protein. From VPO measurements of osmolality (water activity) as a function of the solute concentration in the presence and absence of BSA, we determine the dependence of the solute molarity (C3) on that of BSA (C2) at fixed temperature (37 degrees C), pressure (approximately 1 atm), and osmolality (over the range 0-1.6 molal). After some thermodynamic transformations, these results yield values of [formula: see text] which characterizes the interdependence of solute molalities when temperature, pressure, and the chemical potential of solute 3 are fixed. This form of the preferential interaction coefficient can be interpreted directly in terms of the molecular exclusion or accumulation of the solute (relative to water) near the protein surface. Within experimental uncertainty, [formula: see text] is proportional to m3 both for glycine betaine (0-0.9 m) and for urea (0-1.6 m). For glycine betaine [formula: see text] = -49 +/- 4, a value consistent with the interpretation that this solute is completely excluded from the hydrated surface of BSA, whereas for urea [formula: see text] = 6 +/- 1, which indicates a moderate extent of accumulation at the surface of native BSA. The preferential accumulation of solutes (e.g., urea) that have some binding affinity for a protein can be quantified and interpreted using the two-domain model if the extent of hydration of the protein has been determined using a completely excluded solute (e.g., glycine betaine). Complete exclusion from the local hydration domain surrounding proteins, if general, justifies the use of glycine betaine as a thermodynamic probe of the changes in hydration that accompany protein folding, protein association, and protein-ligand binding interactions.     

The relationship of partner support to outcomes for teenage mothers and their children: a review

OBJECTIVE: To examine the growth response over 3 years of growth hormone deficient (GHD) and non-GHD children who have received growth hormone (GH) in Australia. METHODOLOGY: A retrospective study of a group of patients (1362 children) who commenced GH prior to 1 September 1990. Data were collected at 12 growth centres located in major cities throughout Australia. The data were transferred after informed consent to the national OZGROW database located at the Royal Alexandra Hospital for Children, Sydney, NSW. Of the 1362 children, 898 had received 3 years or more GH therapy and were eligible for this analysis. This cohort was then categorized by diagnosis. Growth response was assessed using height standard deviation score, estimated mature height, growth velocity (GV), GH dose and bone age (years). RESULTS: For children who completed 3 years therapy, the baseline characteristics among diagnostic groups were similar with mean height standard deviation score (SDS) less than -3 SDS (except for the malignancy group) and mean GV ranging from 3.5 to 4.4cm/year. The GV during the first year improved in all groups (7.7-9.4cm/year)followed by an attenuated response during the second and third years of therapy. After 3 years GH therapy the GHD group with peak levels <10 mU/L demonstrated the greatest change in estimated mature height and height SDS. The GHD group with peak levels between > or = 10 but <2OmU/L had a growth response similar to the non-GHD children for all outcome parameters. Change in bone age ranged from 3.1 to 3.8 years with no differences being noted between the diagnostic groups, nor consistently with pubertal status. CONCLUSIONS: Australian GH guidelines have targeted very short children when compared to other series. This large cohort of non-GHD children has demonstrated short-term benefits of GH therapy; however, the long-term benefit remains unclear until these children reach final adult height.     

Experimental studies on the effect of lidocaine on wound healing

Local anesthetics have several effects on wound healing. In experimental studies, procaine at high concentrations has been proved to retard healing in surgical wounds by diminishing the synthesis of mucopolysaccharides and hence probably collagen. Other studies have shown that lidocaine and bupivacaine inhibit collagen synthesis in fibroblast tissue cultures in rats. This study was designed to evaluate the effect of lidocaine on wound healing. An experimental, prospective, comparative, crossover and double-blind study was designed. Forty male guinea pigs, weighing 300 to 600 g, were randomly assigned to two groups. In control group A (20 animals), skin and subcutaneous tissue in a clean wound were incised and infiltrated with regular saline solution; in group B 20 animals were infiltrated with 1% lidocaine. All animals were sacrificed on day 8 and evaluated for breaking strength, number of collagen fibers by morphometry, and histologic examination of collagenization, edema, vascularity, and presence of acute and chronic inflammatory cells. The histopathologic appearance of tissues infiltrated with lidocaine did not vary consistently in relation to collagenization, edema, or acute and chronic inflammatory processes. The mean breaking strength between both groups was not statistically significant (p = 0.120). Important statistical differences were observed in vascularity (p < 0.003) and morphometric results (p < 0.001), where collagen was found in small amounts in the lidocaine group. The results of this study suggest that local infiltration of lidocaine produces significant histopathologic changes, but it does not substantially alter wound healing as there were no differences in the breaking strength of the wounds.     

Physical and nutritional qualities of extruded weaning foods containing sorghum, pearl millet, or finger millet blended with mung beans and nonfat dried milk

Sorghum, pearl millet, and finger millet flours (60% of each) were blended with toasted mung bean flour (30%) and nonfat dry milk (10%) and extruded (Brabender single screw) to make precooked, ready-to-eat, weaning foods. The extruded foods had high cold paste viscosity, but their cooked paste viscosity was lower than that of the respective blends. Chemical scores of the extruded foods were 78 for sorghum, 80 for pearl millet, and 96 for finger millet. Protein digestibility corrected amino acid scores (PD-CAS) were similar for pearl millet (68%) and finger millet (69%); PD-CAS for sorghum was 57%. Total dietary fiber content of the foods ranged from 7.6 to 10.1%, with the soluble dietary fiber content of the foods being about 10% higher than that of the corresponding blends. Extrusion enhanced the in vitro protein digestibility of foods, but no marked difference occurred in the in vitro carbohydrate digestibility among the unprocessed blends and the extruded foods. The net protein ratio, protein efficiency ratio, and biological values were higher for the finger millet food than for the pearl millet food, probably because of the higher lysine content of the finger millet protein.     

Biodistribution of (111)indium-labeled engineered human antibody CTMO1 in ovarian cancer patients: influence of protein dose

Thirty-one patients suspected of having ovarian cancer received a single i.v. injection of radiolabeled (100 MBq (111)In) engineered human CTMO1 (hCTMO1) to investigate its potential as an internalizing drug carrier. hCTMO1 is a complementary-determining region-grafted human IgG4 monoclonal antibody recognizing an ovarian carcinoma-associated antigen, the MUC-1-gene product. The amount of radioactivity was determined in tumor tissue, various normal tissues, including liver biopsies, and blood samples obtained at laparotomy, 6 days after injection of either 0.1 or 1.0 mg hCTMO1/kg of body weight. Circulating antigen-15-3 was measurable in all patients before injection, and immune complex formation was already present at the end of infusion. In the 0.1 mg/kg group, most of the radioactivity was bound to immune complexes, whereas in the 1.0 mg/kg group, most was bound to IgG monomers. Increasing the hCTMO1 dose 10-fold did not influence the overall disappearance of (111)In from the blood, but the elimination half-life of (111)indium bound to immune complexes was increased 2-fold. Uptake in tumor tissue 6 days postinjection at the 0.1 mg/kg dose was 7.6 times higher (P = 0.0009) than in normal tissue and 2.5 times higher (P = 0.03) than in blood. At the 1.0 mg/kg dose, the uptake in tumor tissue was 14.0 times higher (P = 0.0003) than in normal tissue and 8.1 times higher (P = 0.0007) than in blood. Liver activity was substantial (23.7 +/- 10.5 and 18.3 +/- 6.7% of the injected dose/kg for the 0.1 and 1.0 mg/kg dose group, respectively). These results are superior to those found with other clinically tested anti-MUC-1 gene product antibodies. hCTMO1 seems to be a suitable carrier for cytotoxic agents in ovarian carcinoma patients; the better uptake results and tumor-to-blood ratios are obtained at the higher dose of 1.0 mg hCTMO1/kg body weight.     

Magnetic resonance imaging: a useful tool for evaluation of bone prior to implant surgery

OBJECTIVE: To illustrate the potential for use of magnetic resonance imaging (MRI) to gain full sectional information before placement of osseo-integrated dental implants, with no patient exposure to ionising radiation. MATERIALS AND METHODS: Four typical cases are illustrated, the patients being imaged in a one tesla MRI scanner. The setting up of the sequences is explained, along with the use of an imaging/surgical template with gadolinium markers. RESULTS: MRI clearly shows full sectional detail of available bone for safe implant placement, and allows the delineation of cortical and cancellous bone to attain maximum implant length and stability. Vital structures and the floor of the maxillary sinus are clearly shown. CONCLUSIONS: MRI allows the surgeon to assess cases for suitability to place dental implants with confidence. The ability to scan directly at any desired plane, with no reformatting, and to relate this information to a surgical template gives predictable surgery. MRI is a sectional imaging modality giving information about the 3-dimensional relationship of the vital structures, without using ionising radiation. It therefore deserves consideration as an alternative to computed tomography. However, further work is indicated to investigate the relative technical merits of the two imaging modalities.     

Computerized tomography in the diagnosis of subluxation of the distal radioulnar joint

BACKGROUND: The diagnosis of distal radioulnar joint (DRUJ) subluxation is difficult. Routine radiographs are imprecise in clinical analysis. However, the anatomy and dynamic configuration of this articulation have been clearly defined utilizing computerized tomography (CT). Three CT criteria for the evaluation of DRUJ subluxation have been reported: Mino's criteria, the epicenter method and the congruity method. Previous reports discussed these criteria in the analysis of symptomatic DRUJ, but no clear conclusion has been reached. The purpose of this study is to investigate accurate criteria of CT in defining subluxation of the DRUJ. METHODS: Eighty distal radioulnar joints in 40 patients with suspected DRUJ subluxation underwent CT scans of both symptomatic and asymptomatic wrists. The CT scan was obtained through the DRUJ with the forearm in neutral rotation, active full supination and active full pronation. Three CT criteria were used to assess the DRUJ in all positions of unstable and normal wrists. RESULTS: Overall, 54 wrists were included in the final analysis. Seventeen symptomatic wrists had frank DRUJ instability diagnosed from true lateral radiographs, and 11 were reconfirmed from intraoperative pathology. The other 37 wrists had normal DRUJ. Among the three methods, the epicenter method had similar sensitivity to Mino's criteria and the congruity method. However, the epicenter method had much better specificity than Mino's criteria and the congruity method. CONCLUSIONS: For accurate diagnosis of subluxation of the DRUJ, CT scan through the symptomatic DRUJ in neutral rotation, active full supination, active full pronation and analysis with the epicenter method are recommended.     

Chronic blockade of nitric oxide synthase and endothelin receptors during pregnancy in the rat: effect on reactivity of the uterine artery in vitro

Complex tibial condylar fractures are intraarticular fractures with associated lesions of capsule and ligaments, menisci, soft tissue envelope and neurovascular structures. They are in general produced by a high-energy trauma and are usually part of a polytraumatized patient. The frequency for the associated lesions are up 50% for the collateral ligaments, and up to 40% for the cruciate ligaments and the menisci, respectively. The paper presents the crucial steps of clinical and radiological assessment and outlines a concept of treatment, documented by two illustrative cases.