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Large cortical lesions produce enduring forelimb placing deficits in un-treated rats and treatment with NMDA antagonists or anti-oxidant drugs induces behavioral recovery.

Previous studies have utilized a lesion model of cortical injury that produces transient behavioral impairments to investigate the recovery of function process. To better understand the recovery process, it would be beneficial to use a lesion model that produces more severe, enduring, behavioral impairments. The purpose of experiment 1 was to validate whether large lesions of the sensorimotor cortex (SMC), which included the rostral forelimb and caudal forelimb regions, produced enduring behavioral deficits. Rats were given large unilateral electrolytic lesions of the SMC, administered either the N-methyl-D-aspartate (NMDA) antagonist, MK-801 or saline 16 h after injury, and tested on a battery of behavioral tests. Enduring behavioral deficits were observed, for at least 6 months, on two tests of forelimb placing while transient deficits were observed on the foot-fault and somatosensory neutralization tests. Administration of MK-801 facilitated recovery on the somatosensory neutralization test; however, it did not induce recovery on either forelimb placing test. A second experiment was performed to determine if earlier administration of MK-801, the NMDA antagonist magnesium chloride (MgCl(2)), or the anti-oxidant N-tert-butyl-alpha-phenylnitrone (PBN) could induce behavioral recovery in this chronic model. Treatment with these drugs induced behavioral recovery on the forelimb placing tests, whereas, the saline-treated rats did not show any signs of behavioral recovery for at least 3 months. Anatomical analysis of the striatum showed that MK-801 and MgCl(2) but not PBN reduced the extent of lesion-induced striatal atrophy. These results suggest that administration of MK-801, MgCl(2), or PBN shortly after cortical injury can induce recovery of function when recovery is otherwise not expected in un-treated rats.

Animals↗

Quantitative contributions of cholesterol and the individual classes of phospholipids and their degree of fatty acyl (un)saturation to membrane fluidity measured by fluorescence polarization.

Steady-state fluorescence polarization (P) measurements, using the probe 1,6-diphenyl-1,3,5-hexatriene, in a large variety of well-defined liposomes at 25 degrees C allowed a quantitative description of the contributions of cholesterol, sphingomyelin, and (un)saturation of fatty acyl groups in the various phospholipids to the structural order (or the mutual affinity) of membrane lipids. The P values for liposomes prepared from lipid extracts of natural (purified) membranes of various origins could be more or less predicted (calculated) from the relative contributions of the individual lipid components. In all cases, the polarization varied with the cholesterol/phospholipid molar ratio (C/PL) according to the equation P = Pplat -(Pplat -Pzero) exp(-alpha C/PL), in which Pzero refers to the polarization without cholesterol and Pplat is a maximal plateau value, reached at a high C/PL (greater than 1). The "cholesterol-ordering coefficient" alpha of the phospholipids was found to increase with the fraction of sphingomyelin or dipalmitoylphosphatidylcholine molecules, indicating that the susceptibility of phospholipids to be ordered by cholesterol is increased by these compounds. Pzero increases curvilinearly with the fraction of either of these molecules. Pplat increases linearly with the fraction of saturated acyl chains for most phospholipids. Highly unsaturated fatty acyl chains (e.g., 20:4 and 22:6) strongly depress Pplat but not Pzero. The results suggest that such phospholipids are unlikely to associate with cholesterol and may thus create extremely fluid membrane domains. The disproportionation of cholesterol in the cell can be understood by the differing composition of the phospholipids in plasma membranes and endomembranes and their ordering susceptibility (affinity) toward cholesterol.

Animals↗

Changing the transition state for protein (Un) folding.

(Un)folding transition states of Saccharomyces cerevisiae iso-1-ferri- and ferrocytochromes c were studied using equilibrium and kinetic denaturation experiments. The wild-type protein and the global suppressor variant, N52I (isoleucine replaces asparagine 52), were examined. Denaturation was induced by guanidinium chloride (GdmCI) and monitored by circular dichroism (CD) spectropolarimetry without stopped-flow devices. Soret CD spectra indicate that thermal and GdmCl denatured states are different, and heat is the more effective denaturant. Equilibrium data show that the high stability of ferrocytochrome c can be rationalized as a requirement to bury the oxidation-induced positive charge and remain folded under physiological conditions. Kinetic data are monoexponential and permit characterization of the rate-limiting transition state for unfolding as a function of [GdmCl]. For the oxidized wild-type protein, the transition state solvent accessibility is nearly the same as that of the denatured state. Three perturbations, reducing the wild-type protein, reducing the N52I variant, and substituting position 52 in the oxidized protein, change the free energy and solvent accessibility of the transition state. In contrast, substituting position 52 in the reduced protein apparently does not change the transition state solvent accessibility, allowing more detailed characterization. In the reduced proteins' transition states at 4.3 M GdmCl, the position 52 side chain is in a denatured environment, even though transition state solvent accessibility is only one-third that of the denatured state (relative to the native state).

Asparagine↗

Measurement of un-ionized ammonia in complex mixtures.

The toxicity of un-ionized ammonia, NH3 (aq), in anaerobic digestion of high-nitrogen wastes has been researched extensively. Previous estimates of NH3 (aq) concentration have relied on a simple speciation approach, based only on the acid dissociation constant and the sample pH and total ammonia concentration. The distinction between concentration and chemical activity has generally not been made, despite the potential for resulting errors in the calculation of NH3 (aq) concentration, and the greater applicability of activity to toxicity work. The currently accepted approach for estimating NH3 (aq) concentration is based on assumptions that are not valid in digested animal manure or other concentrated wastes. This work presents an approach for directly measuring NH3 (aq) activity in complex mixtures using gaseous/aqueous equilibrium across microporous tubing. Application of this approach to anaerobic digester samples confirms that the currently accepted approach is not accurate; it overestimated NH3 (aq) activity in unaltered samples by 45-200%. Previous work on the toxicity of ammonia to methanogenesis has probably overestimated the tolerance of consortia to NH3 (aq), due to overestimation of concentrations. The method introduced here is expected to be useful in a range of research on ammonia toxicity and volatilization.

Ammonia↗

Prevalence and determinants of hypertension in an un-industrialised rural population of North India.

Recent studies have indicated a rising prevalence of hypertension in rural and urban areas of India. A population-based survey was carried out during 1994-1995 in seven rural and non-industrialised villages around RaipurRani block in the state of Haryana, India, to determine the prevalence of hypertension and its associated risk factors. A total of 2559 individuals (86% of the eligible population) in the 16 to 70-year age group were interviewed using a pre-tested structured questionnaire to find out the lifestyle characteristics. Three blood pressure (BP) readings were recorded with a random zero sphygmomanometer at three different times. One hundred and fourteen individuals (4.5%) were found to be hypertensive according to JNC V criteria (BP of > or = 140/90 mm Hg). Mean systolic and diastolic BPs were 116.9 and 71.7 mmHg in males and 119.1 and 72.7 mm Hg in female subjects respectively (P < 0.001). Females had significantly higher prevalence of hypertension than males (5.8% vs 3.0%, P < 0.05). Mean age of hypertensives (50.3 +/- 13.5 years) was higher than normotensives (34.9 +/- 14.5 years, P < 0.001). The prevalence of various risk factors among hypertensives as compared to normotensives were alcohol consumption (43.2% vs 23.1%, only among males, P < 0.001), higher economic status (P < 0.001) and smoking (43% vs 41.5%, P > 0.05). In addition hypertensives had higher mean weight (53.8 kg vs 48.4 kg, P < 0.001) and higher body mass index (21.5 vs 18.9 kg/m2, P < 0.001). Analysis showed that advancing age, sedentary lifestyle, higher alcohol consumption and higher body mass index are the risk factors for hypertension in the rural un-industrialised population of India.

Adolescent↗

Health problems among UN refugees at a family medical centre in Ankara, Turkey.

OBJECTIVES: Political lability in the Near East has brought about the migration of refugees from adjacent countries to Turkey in recent years. To provide an effective health service for refugees, a needs assessment has to be done. UN refugees referring to a family medical centre located in Ankara, Turkey, were therefore investigated for health problems. DESIGN: Medical records were studied retrospectively for age distribution, gender, origin, diagnoses, type of treatment and referral to a secondary health care setting. SUBJECTS: 212 refugees of different countries (mostly from Iraq, Iran and Palestine). RESULTS: Infectious disease was the most often diagnosed condition. Post-traumatic stress disorders could be observed in 12% of refugees. CONCLUSION: The family physician must be careful not to misdiagnose these disorders during medical examination. Most disease can be diagnosed and treated in family practice. Special care must be taken in the case of mental disorders.

Adult↗

Degradation of hyaluronate by Streptococcus intermedius strain UNS 35.

Streptococcus intermedius strain UNS 35, a brain abscess isolate, produced extracellular hyaluronidase when grown in brain heart infusion broth. Chemical assays with this enzyme indicated that hyaluronate depolymerisation resulted in the formation of carbohydrate moieties with N-acetylglucosamine at the reducing terminal and containing an unsaturated carbon-carbon double bond. The nature of the products of this hyaluronidase were investigated further by high-field (400 MHz) proton (1H) NMR spectroscopy. Treatment of hyaluronate with the enzyme resulted in a series of new, sharp resonances in spectra (acetamido methyl group singlets located at 2.03 and 2.07 ppm, sugar ring proton multiplets in the 3.5-4.2 ppm chemical shift range, and doublets at 5.16 and 5.87 ppm) characteristic of low-M(r) oligosaccharide species, predominantly those containing glucuronosyl residues with delta 4,5-carbon-carbon double bonds. Comparison of spectra acquired from hyaluronidase-treated samples with that of an authentic sample of 4-deoxy-L-threo-hex-4-enopyranosyluronic-acid-N-acetylglucosamine (delta UA GlcNAc) indicated that this disaccharide was a major product arising from the actions of this enzyme. When used in minimal media, hyaluronate supported growth of S. intermedius, with lactate as the major metabolic end-product.

Carbohydrate Sequence↗

Purification and properties of a novel glycosaminoglycan depolymerase from Streptococcus intermedius strain UNS 35.

A glycosaminoglycan (GAG) depolymerase that acts on chondroitin sulphate A (CS-A), chondroitin sulphate C (CS-C) and hyaluronic acid (HA) was purified to apparent homogeneity from a culture of Streptococcus intermedius, strain UNS 35, grown in minimal medium supplemented with CS-A as the sole carbon source. The enzyme was purified by ammonium sulphate precipitation followed by serial chromatography on DEAE Trisacryl M, CM Trisacryl M and heparin-agarose. SDS-PAGE analysis of the purified enzyme yielded a single band with a mol.wt of c. 83000. The purified GAG depolymerase was unusual in its substrate specificity. The enzyme was initially regarded as a CS depolymerase because of its induction by CS-A. However, the GAG depolymerase exhibited greatest activity against HA, whereas the degradation rates of CS-A and CS-C were c. 8% and 2%, respectively, of the rate with HA. On this basis the enzyme could be classified as a hyaluronidase rather than a CS depolymerase. The pH optimum was around neutrality and the enzyme was unusual in having a high pI of approximately 9.3.

Chondroitinases and Chondroitin Lyases↗

Predictive (un)distortion model and 3-D reconstruction by biplane snakes.

This paper is concerned with the three-dimensional (3-D) reconstruction of coronary vessel centerlines and with how distortion of X-ray angiographic images affects it. Angiographies suffer from pincushion and other geometrical distortions, caused by the peripheral concavity of the image intensifier (II) and the nonlinearity of electronic acquisition devices. In routine clinical practice, where a field-of-view (FOV) of 17-23 cm is commonly used for the acquisition of coronary vessels, this distortion introduces a positional error of up to 7 pixels for an image matrix size of 512 x 512 and an FOV of 17 cm. This error increases with the size of the FOV. Geometrical distortions have a significant effect on the validity of the 3-D reconstruction of vessels from these images. We show how this effect can be reduced by integrating a predictive model of (un)distortion into the biplane snakes formulation for 3-D reconstruction. First, we prove that the distortion can be accurately modeled using a polynomial for each view. Also, we show that the estimated polynomial is independent of focal length, but not of changes in anatomical angles, as the II is influenced by the earth's magnetic field. Thus, we decompose the polynomial into two components: the steady and the orientation-dependent component. We determine the optimal polynomial degree for each component, which is empirically determined to be five for the steady component and three for the orientation-dependent component. This fact simplifies the prediction of the orientation-dependent polynomial, since the number of polynomial coefficients to be predicted is lower. The integration of this model into the biplane snakes formulation enables us to avoid image unwarping, which deteriorates image quality and therefore complicates vessel centerline feature extraction. Moreover, we improve the biplane snake behavior when dealing with wavy vessels, by means of using generalized gradient vector flow. Our experiments show that the proposed methods in this paper decrease up to 88% the reconstruction error obtained when geometrical distortion effects are ignored. Tests on imaged phantoms and real cardiac images are presented as well.

Angiography, Digital Subtraction↗

Incidental diagnosis of diseases on un-enhanced helical computed tomography performed for ureteric colic.

BACKGROUND: Patients presenting in the emergency room with flank pain suggestive of acute ureteric colic may have alternative underlying conditions mimicking ureteric stones. An early diagnosis and appropriate treatment for other causes of flank pain is important. The majority of centers around the world are increasingly using un-enhanced helical CT (UHCT) for evaluation of ureteric colic. This study was conducted to determine the incidence and spectrum of significant incidental diagnoses established or suggested on UHCT performed for suspected renal/ureteric colic. METHODS: Urologist and radiologist reviewed 233 consecutive UHCT, performed for suspected renal/ureteral colic along with assessment of the medical records. Radiological diagnoses of clinical entities not suspected otherwise were analyzed. All other relevant radiological, biochemical and serological investigations and per-operative findings were also noted. RESULTS: Ureteral calculi were identified in 148 examinations (64%), findings of recent passage of calculi in 10 (4%) and no calculus in 75 examinations (32%). Overall the incidental findings (additional or alternative diagnosis) were found in 28 (12%) CT scans. Twenty (71%) of these diagnoses were confirmed by per-operative findings, biopsy, and other radiological and biochemical investigations or on clinical follow up. CONCLUSION: A wide spectrum of significant incidental diagnoses can be identified on UHCT performed for suspected renal/ureteral colic. In the present series of 233 consecutive CT examinations, the incidence of incidental diagnosis was 12%.

Colic↗

Phase I safety study of 0.5% PRO 2000 vaginal Gel among HIV un-infected women in Pune, India.

BACKGROUND: The objective of this study was to evaluate the safety of twice daily, intra-vaginal use of 0.5% PRO 2000 Gel for fourteen days in HIV un-infected women at lower as well as higher risk for HIV acquisition, in Pune, India. METHODS: Forty-two eligible volunteers (30 low-risk and 12 high-risk) were given 0.5% PRO 2000 Gel for intra-vaginal application twice daily for 14 consecutive days. RESULTS: Twenty-four participants (57%, 95% CI 41%-72%) experienced at least one adverse event (AE) judged to be possibly related to the product use. There were 17 (40%, 95% CI 26%-57%) mild AEs and 7 (17%, 95% CI 7%-31%) moderate AEs. There were no serious adverse events and no AEs judged probably or definitely related to product use. Genitourinary discomfort was reported by 2/30 (6.67%) participants in the low-risk cohort as compared to 4/12 (33.3%) women in the high-risk cohort (p = 0.03). Intermenstrual bleeding was reported in 2/30 (6.7%, 95% CI 1.0-22.1) women from the low risk cohort and 3/12 (25%, 95% CI 5.5-57.2) women from the high-risk cohort. One participant showed mild elevation of blood gamma glutamyl transferase and two showed mild elevations in total bilirubin. None of the participants showed detectable PRO 2000 in their blood after 14 days of product use. CONCLUSION: 0.5% PRO 2000 Gel appeared to be safe when used twice-daily by sexually active HIV-uninfected women from Pune, India. Although genitourinary discomfort and metrorrhagia were more common in the high-risk cohort, ongoing Phase II/IIb trial would provide data for generalization of this finding.

Journal Article↗

Sustainable Cities Programme: a joint UN-HABITAT-UNEP facility on the urban environment with participation of the Dutch government.

The fundamental objective of the Sustainable Cities Programme is to promote environmentally sustainable local development to more fully realize the vital contributions that urban areas make to over-all social and economic development by: (1) enhancing efficiency in the use of local environmental resources, reducing environmental risks, and strengthening application of environmental conventions and agreements with growing regard to the Climate Change Protocol; (2) reducing poverty by promoting more equitable access to resources and environmental services; (3) mobilizing and strengthening local capacities to plan, co-ordinate, and manage sustainable local development in partnership; and (4) combining the complementary strengths of UN-HABITAT, UNEP, and other partners in support of Agenda 21, and the Habitat Agenda sustainable development commitments including improved local environmental governance.

City Planning↗

Re-attachment of the un-united trochanter in Charnley low friction arthroplasty.

In a prospective study, a double crossover wire with a compression spring was used to re-attach 52 un-united trochanters at revision operations on total hip arthroplasties. Bony union was achieved in 42 (81%) and was not influenced by the duration of the nonunion or the separation gap. The new method compared favourably with earlier revisions at which other methods of trochanteric re-attachment had been used.

Adult↗

Are UN peacekeepers at risk for suicide?

Media reports connecting UN peacekeeping duties by Canadian soldiers to their subsequent suicide prompted this study of peacekeeping as suicide risk. In a case-control design we retrospectively compared 66 suicides in the Canadian military between 1990 and 1995 with two control groups: (a) 2,601 controls randomly selected from the electronic military database and (b) 66 matched controls with complete personnel and medical data. We found no increased risk of suicide in peacekeepers except among a subgroup of air force personnel. Here confounding individual factors, isolation from supports, and possibly inadequate preparation for deployment elucidated their suicides. Theater of deployment (e.g., Bosnia) did not affect the suicide rate. Military suicides experienced psychosocial stresses and psychiatric illness more often than their matched controls. We conclude that although peacekeeping per se does not increase overall suicide risk, military life-styles may strain interpersonal relationships, encourage alcohol abuse, and contribute to psychiatric illness and suicide in a minority of vulnerable individuals irrespective of peacekeeping assignment. Careful selection, and preparatory military training that encourages intragroup bonding and mutual support, may protect against suicide risk.

Adult↗

Clinical and subclinical hepatitis A occurring after immunoglobulin prophylaxis among Swedish UN soldiers in Sinai.

This study was performed to investigate the efficiency of 5 ml of 16.5% immunoglobulin (Ig) with an antibody titer against hepatitis A (anti-HAV) of 1:4000, using the HAVAB RIA technique, as pre-infection prophylaxis in 610 Swedish UN soldiers stationed in Sinai for 6 months. Sera were collected from 553 of these soldiers before, during, and after their service and were tested by the HAVAB technique for anti-HAV. Only 13 of 553 (2.4%) were immune before their service. During the first 5 months in Sinai, only one subclinical case of hepatitis A occurred among the men. Thereafter, two subclinical and four clinical cases occurred, although one of the subclinical cases and the four clinical ones did not occur until after the 6-month period. Thus, the Ig prophylaxis scheme used seems to offer almost complete passive protection for 5 months.

Adult↗

Phenytoin-induced gingival overgrowth in un-cooperated epilepsy patients.

Phenytoin-induced gingival overgrowth is a well-known and frequently reported gingival lesion, which was first detected in 1939. However, there are conflicts in the literature about the agents which affect the severity of the lesion. Un-cooperative dental patients are one of the most unsuccessfully treated periodontal patient groups because of the difficulty in maintaining their oral hygiene. This case report consists of two cases with the same characteristics: phenytoin usage, comprehension and speech defects and poor oral hygiene, but each case differs in the duration of the phenytoin therapy. Both of the cases received scaling, root planning and a gingivectomy.

Adult↗

Doxorubicin binds to un-phosphorylated form of hNopp140 and reduces protein kinase CK2-dependent phosphorylation of hNopp140.

Human nucleolar phosphoprotein p140 (hNopp140) is a nucleolar phosphoprotein that can bind to doxorubicin, an anti-cancer agent. We have examined the interaction between hNopp140 and doxorubicin as well as the folding property of hNopp140. Also, the effects of ATP and phosphorylation on the affinity of hNopp140 to doxorubicin are investigated by affinity dependent co-precipitation and surface plasmon resonance methods. Doxorubicin preferentially binds to un-phosphorylated form of hNopp140 with a KD value of 3.3 x 10(-7) M. Furthermore, doxorubicin reduces the protein kinase CK2-dependent phosphorylation of hNopp140, indicating that doxorubicin may perturb the cellular function of hNopp140 by reducing the protein kinase CK2-dependent phosphorylation of hNopp140. Low contents of the secondary structures of hNopp140 and the fast rate of proteolysis imply that hNopp140 has a high percentage of flexible regions or extended loop structures.

CDC2 Protein Kinase↗

[A viscosimetric study of thermally induced release of ds-DNA from Un phage].

The thermally induced ejection of DNA from the head of the Un phage was studied by viscosimetry, pH was used as a variable external factor. The results obtained suggest that the infection of the bacterium by the phage occurs in the pH range 6-10 rather than in the acidic medium (pH 4-5) because the infection can take place only if the DNA is completely ejected from the phage head. It was shown that the ejection of DNA upon dilution of the initial concentration of the phage depends on the time required for the equilibrium of the phage suspension in the corresponding buffer solution to be established after which the measurements can be performed. In our experiments, this time interval was 24 h.

Bacteriophages↗