Altered muscarinic and nicotinic receptor densities in cortical and subcortical brain regions in Parkinson's disease

Muscarinic and nicotinic cholinergic receptors and choline acetyltransferase activity were studied in postmortem brain tissue from patients with histopathologically confirmed Parkinson's disease and matched control subjects. Using washed membrane homogenates from the frontal cortex, hippocampus, caudate nucleus, and putamen, saturation analysis of specific receptor binding was performed for the total number of muscarinic receptors with [3H]quinuclidinyl benzilate, for muscarinic M1 receptors with [3H]pirenzepine, for muscarinic M2 receptors with [3H]oxotremorine-M, and for nicotinic receptors with (-)-[3H]nicotine. In comparison with control tissues, choline acetyl-transferase activity was reduced in the frontal cortex and hippocampus and unchanged in the caudate nucleus and putamen of parkinsonian patients. In Parkinson's disease the maximal binding site density for [3H]quinuclidinyl benzilate was increased in the frontal cortex and unaltered in the hippocampus, caudate nucleus, and putamen. Specific [3H]pirenzepine binding was increased in the frontal cortex, unaltered in the hippocampus, and decreased in the caudate nucleus and putamen. In parkinsonian patients Bmax values for specific [3H]oxotremorine-M binding were reduced in the cortex and unchanged in the hippocampus and striatum compared with controls. Maximal (-)-[3H]nicotine binding was reduced in both the cortex and hippocampus and unaltered in both the caudate nucleus and putamen. Alterations of the equilibrium dissociation constant were not observed for any ligand in any of the brain areas examined. The present results suggest that both the innominatocortical and the septohippocampal cholinergic systems degenerate in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS

Cumulate causes for the low contents of sulfide-loving elements in the continental crust

Despite the economic importance of chalcophile (sulfide-loving) and siderophile (metal-loving) elements (CSEs), it is unclear how they become enriched or depleted in the continental crust, compared with the oceanic crust. This is due in part to our limited understanding of the partitioning behaviour of the CSEs. Here I compile compositional data for mid-ocean ridge basalts and subduction-related volcanic rocks. I show that the mantle-derived melts that contribute to oceanic and continental crust formation rarely avoid sulfide saturation during cooling in the crust and, on average, subduction-zone magmas fractionate sulfide at the base of the continental crust prior to ascent. Differentiation of mantle-derived melts enriches lower crustal sulfide- and silicate-bearing cumulates in some CSEs compared with the upper crust. This storage predisposes the cumulate-hosted compatible CSEs (such as Cu and Au) to be recycled back into the mantle during subduction and delamination, resulting in their low contents in the bulk continental crust and potentially contributing to the scarcity of ore deposits in the upper continental crust. By contrast, differentiation causes the upper oceanic and continental crust to become enriched in incompatible CSEs (such as W) compared with the lower oceanic and continental crust. Consequently, incompatible CSEs are predisposed to become enriched in subduction-zone magmas that contribute to continental crust formation and are less susceptible to removal from the continental crust via delamination compared with the compatible CSEs

Song variation of the South Eastern Indian Ocean pygmy blue whale population in the Perth Canyon, Western Australia

Sea noise collected over 2003 to 2017 from the Perth Canyon, Western Australia was analysed for variation in the South Eastern Indian Ocean pygmy blue whale song structure. The primary song-types were: P3, a three unit phrase (I, II and III) repeated with an inter-song interval (ISI) of 170–194 s; P2, a phrase consisting of only units II & III repeated every 84–96 s; and P1 with a phrase consisting of only unit II repeated every 45–49 s. The different ISI values were approximate multiples of each other within a season. When comparing data from each season, across seasons, the ISI value for each song increased significantly through time (all fits had p < 0.001), at 0.30 s/Year (95%CI 0.217–0.383), 0.8 s/Year (95% CI 0.655–1.025) and 1.73 s/Year (95%CI 1.264–2.196) for the P1, P2 and P3 songs respectively. The proportions of each song-type averaged at 21.5, 24.2 and 56% for P1, P2 and P3 occurrence respectively and these ratios could vary by up to ± 8% (95% CI) amongst years. On some occasions animals changed the P3 ISI to be significantly shorter (120–160 s) or longer (220–280 s). Hybrid song patterns occurred where animals combined multiple phrase types into a repeated song. In recent years whales introduced further complexity by splitting song units. This variability of song-type and proportions implies abundance measure for this whale sub population based on song detection needs to factor in trends in song variability to make data comparable between seasons. Further, such variability in song production by a sub population of pygmy blue whales raises questions as to the stability of the song types that are used to delineate populations. The high level of song variability may be driven by an increasing number of background whale callers creating ‘noise’ and so forcing animals to alter song in order to ‘stand out’ amongst the crowd

Brain muscarinic cholinergic receptors in Huntington's disease

Muscarinic cholinergic receptors and choline acetyltransferase (ChAT) activity were studied in postmortem brain tissue from patients with Huntington's disease and matched control subjects. In comparison with controls, reductions in ChAT activity were found in the hippocampus, but not in the temporal cortex in Huntington's disease. Patients with Huntington's disease showed reduced densities of the total number of muscarinic receptors and of M-2 receptors in the hippocampus while the density of M-1 receptors was unaltered. Muscarinic receptor binding was unchanged in the temporal cortex. These results indicate a degeneration in Huntington's disease of the septo-hippocampal cholinergic pathway, but no impairment of the innominato-cortical cholinergic system

Terguride stimulates locomotor activity at 2 months but not 10 months after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets

The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on normosensitive receptors but shows DA agonistic properties at supersensitive DA receptors. Such a compound could offer an alternative to the treatment of Parkinson's disease with indirect or direct DA agonists. The present study compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets with its effects in animals rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity in naive common marmosets, similar to its effects in rodents and in line with the DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months previously and exhibiting pronounced behavioural motor deficits, terguride stimulated locomotor activity, showing DA agonistic properties under these conditions. In contrast, the locomotor activity of animals that had recovered from MPTP treatment 10 months previously was not altered by terguride. It is concluded that terguride has anti-akinetic efficacy in this primate model of Parkinson's disease. In addition, terguride offers a unique opportunity to differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP treatment in this primate species

Urinary tract infection in type 2 diabetic patients: risk factors and antimicrobial pattern

Background: Diabetes increases the risk of infection and the commonest amongst them are the ones involving the genitourinary tract. Diabetic patients are found to have an increase in the risk of developing urinary tract infection (UTI) by 60%. The study aimed to determine the causative pathogens and their antimicrobial pattern, identify risk factors associated in type 2 diabetic subjects having UTI. Methods: This was an observational study conducted in the medicine unit of a tertiary care hospital over a period of 8 months. A total of 619 (M:F 289:330) type 2 diabetic subjects were studied. History, clinical examinations, and the duration of diabetes were recorded in all patients at admission. Diabetes was diagnosed based on the WHO criteria. An immunoturbidimetric method was used to estimate glycosylated hemoglobin (HbA1C%). Diagnosis of UTI was made from midstream urine samples of patients if the urine cultures has >103 to >105 colony forming units (CFUs)/mL of a pathogen.Results: Among the 619 diabetic patients 220 patients had pus cells in urine but 72 patients had insignificant colony count. 90 (60.8%) patients were more than 60 years old, 48 (32.4%) were in the age group of 40-60 years and 10 (6.7%) were less than 40 years old. Among the 148 patients studied 52 (35.1%) were males and 96 (64.9%) were females. 116 (78.4%) had diabetes for more than 15 years and the rest had a duration lesser than 15 years. The HbA1C of patients with and without UTI were 10.2 ± 1.6 and 8.4 ± 1.3 respectively. Gram negative bacilli were isolated from 129 (87.2%) patients which included E. coli in 75 (50.7%), Klebsiella in 30 (20.3%), Pseudomonas species in 12 (8.1%) and Citrobacter in 12 (8.1%). Gram positive cocci were responsible for UTI in 15(10.1%) of subjects including Enterococcus in 13 (8.9%) and Staphylococcus in 2 (1.3%). Gram negative bacilli including E. coli, the Klebsiella species, pseudomonas and Citrobacter had good response to piperacillin-tazobactum, cefoperazone sulbactum, imipenam and amikacin. Gram positive cocci (Enterococcus and Staphylococcus) responsible for UTI showed good susceptibility to vancomycin (81 and 94% respectively) but a high resistance to ciprofloxacin and tetracyclines (68 and 57% respectively).Conclusions: Female gender, age and duration of diabetes were found to have increased risk factors for developing UTI in diabetes. Escherichia coli was the commonest organism causing UTI in diabetes which showed good response to piperacillin/tazobactum, cefoperazone-sulbactum, imipenam and amikacin.

Ergebnisse der qualitativen WPP Studie der Charité – Universitätsmedizin Berlin

Introduction: University medicine in Germany is a highly hierarchically regulated system due to complex processes as well as the different powers of the status groups and their professional socialization. Sexual harassment in the social and historical context of power and inequality is inherent in hierarchical structures, which is evidenced by the high prevalence in clinics of international/national studies. From the limited international data situation it can be concluded that hierarchy, power relations, stress burden and corporate culture play a significant role in medicine and care. For this reason, culture-specific protection and prevention concepts are indispensable for the employees in the hospital environment, until now the topic has been re-searched only to a limited time internationally/nationally. Methods: As part of the WPP study on the study of sexual harassment in a clinical en-vironment, data on a) incidence b) prevention c) implementation were generated in order to comprehensively address the multigroup phenomenon. In the qualitative part of the study, protection prevention strategies were investigated using semi-structured guide interviews with 15 doctors and 15 nurses. The qualitative method provided in-sights as well as recommendations for action from the clinical environment, which are reflected in the professional reality of the interviewees. Results: From the perspective of the interviewees, findings and recommendations for action on protection and prevention options could be analysed at an individual strategic and structural level The Management Board should be committed to a zero-tolerance strategy and appropriate institutional prevention strategies. Especially personnel-responsible managers of the clinics/departments/institutes have the responsibility in the case of incidents of sexual harassment in the case of intervention. Managers serve as role models for a respectful and appreciative working atmosphere and should reflect the diversity of employees. Both professions cite intervention and relief techniques for self-protection in Patient_innen and family settings. At nuisance events at the horizontal level, situational strategies from over-ignored to direct response of practitioners were applied. Conclusion: The results presented show that due to the high prevalence of sexual harassment in the clinical environment, the need for protection and prevention measures is essential at all levels of the company. In order to protect sexual harassment, combinations of individualised interventions and in-depth prevention options were mentioned in the organisational structures. A culturally specific company agreement that is customary to the company provides a necessary basis for proactive handling of institutional prevention events.Einführung: Die Universitätsmedizin in Deutschland ist aufgrund von komplexen Abläufen sowie der unterschiedlichen Machtbefugnisse der Statusgruppen und deren Berufssozialisation ein stark hierarchisch reglementiertes System. Aus der limitierten internationalen Datenlage lässt sich schlussfolgern, dass Hierarchie, Machtverhältnis-se, Stressbelastung und Unternehmenskultur in der Medizin und Pflege eine erhebliche Rolle spielen. Sexuelle Belästigung im Kontext von Macht und (Geschlechter-) Ungleichverteilung ist hierarchischen Strukturen inhärent, welches durch die hohe Prävalenz in Kliniken internationalen/nationalen Studien belegt wird. Daher sind Schutz- und Präventionskonzepte für die Beschäftigten im Klinikambiente unerlässlich, bis dato wurde die Thematik international/national nur limitiert erforscht. Methodik: In Rahmen der dargestellten WPP-Studie zur Erforschung von sexueller Belästigung im klinischen Ambiente wurden Daten zur a) Inzidenz b) Prävention c) Implementierung generiert, um dem multifraktionellen Phänomen umfassend zu begegnen. Im qualitativen Studienteil wurden Schutz- und Präventionsstrategien anhand von semistrukturierten Leitfadeninterviews mit 15 Ärztinnen und 15 Pflegekräften unter-sucht. Die qualitative Methode lieferte dabei Erkenntnisse sowie Handlungsempfehlungen aus dem klinischen Umfeld, die sich an der beruflichen Realität der Interviewten abbilden. Die Auswertung des transkribierten Interviewmaterials erfolgte mit der strukturierten Inhaltsanalyse nach Philipp Mayring. Das zentrale Vorgehen bildet dabei die Analyse anhand der deduktiven und induktiven Kategorienbildung. Ergebnisse: Aus der Perspektive der Interviewten konnten Erkenntnisse und Hand-lungsempfehlungen zum Schutz und Präventionsoptionen auf individueller strategischer und struktureller Ebene analysiert werden. Beide Berufsgruppen nennen Interventions- und Entlastungstechniken zum Selbstschutz in Patient_innen- und Angehörigensettings. Auf Belästigungsereignisse auf horizontaler Ebene werden situativ Strategien von Überhören bis direktes Ansprechen der Ausübenden angewandt. Die Berufsgruppen benennen die Null-Toleranz-Strategie des Management-Boards mit entspre¬chenden institutionellen Präventionsstrategien zur Unterstützung der Strategie. Personalverantwortliche Führungskräfte der Kliniken/Abteilungen/Institute haben eine Vorbildfunktion im Interventionsgeschehen sowie für eine respektvolle und wertschätzende Arbeitsatmosphäre und sollen der Diversität der Beschäftigten gerecht werden. Schlussfolgerungen: Die dargestellten Ergebnisse zeigen auf, dass aufgrund der hohen Prävalenz von sexueller Belästigung im klinischen Umfeld die Notwendigkeit von Schutz- und Präventionsmaßnahmen, auf allen Unternehmensebenen unerlässlich sind. Zum Schutz vor sexueller Belästigung wurden Kombinationen von individualisierten Interventionen sowie in die Organisationsstrukturen eingehende Präventionsoptionen genannt. Kulturspezifische, dem Unternehmen angepasste Maßnahmen stellen dabei eine notwendige Grundlage zum proaktiven Umgang im institutionellen Präventionsgeschehen dar

ATP-Binding Cassette Systems of Brucella

Brucellosis is a prevalent zoonotic disease and is endemic in the Middle East, South America, and other areas of the world. In this study, complete inventories of putative functional ABC systems of five Brucella species have been compiled and compared. ABC systems of Brucella melitensis 16M, Brucella abortus 9-941, Brucella canis RM6/66, Brucella suis 1330, and Brucella ovis 63/290 were identified and aligned. High numbers of ABC systems, particularly nutrient importers, were found in all Brucella species. However, differences in the total numbers of ABC systems were identified (B. melitensis, 79; B. suis, 72; B. abortus 64; B. canis, 74; B. ovis, 59) as well as specific differences in the functional ABC systems of the Brucella species. Since B. ovis is not known to cause human brucellosis, functional ABC systems absent in the B. ovis genome may represent virulence factors in human brucellosis

Analysis of effects in wheat of high temperature on grain filling attributes estimated from mathematical models of grain filling

Compared with growth at 20/15 xC (day/night), exposure of wheat (Triticum aestivum L.) plants to moderately high temperature (30/25 xC) significantly decreased grain weight through shortening the duration of grain filling, combined with small (or no) positive increases in the rate of grain filling. Several mathematical models of grain filling were assessed for their suitability as means of analysing these effects of temperature. The ordinary logistic model was found to be the most appropriate model and was used for the analysis of grain filling responses in four cultivars differing in their responses. Genotypic variation in response to temperature was observed for both rate and duration of grain filling, but the variation for the duration of grain filling among cultivars was small at the higher temperature. Significant correlation was found between single grain weight with the rate, but not with the duration, of grain filling at high temperature, which indicated an important role for synthetic processes involved in grain filling in the temperature sensitivity of wheat cultivars. As they are independent traits, both rate and duration are required selection criteria for the improvement of heat tolerance. Responses of one attribute estimated from the logistic model, the inflection point of the course of grain filling, may give insight into a temperature response that is distinguishable from that associated with the duration of grain filling. The inflection point appears to be worth including as a criterion in selecting for high temperature tolerance in wheat.M. Zahedi and C. F. Jenne