Effect of isoproterenol (ISO) on rat heart,liver, kidney,and muscle tissue levels of zinc,copper, and magnesium

X-ray fluorescence and atomic absorption spectrometry were used to measure the concentrations of zinc, copper, and magnesium in the heart, liver, skeletal muscle, and kidney following isoproterenol-induced myocardial necrosis in male albino rats. Serum activities of lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and glutamic oxaloacetic transaminase (SGOT) were also measured. There was depletion of myocardial zinc, copper, and magnesium on d 1, followed by an uptake of all these elements on d 2. The liver showed a significant uptake of magnesium, along with depletion of copper. There was no change in the kidney and skeletal muscle concentrations of these elements. Possible explanations for the observed changes and their therapeutic significance are presented.     

Null Mutations in LTBP2 Cause Primary Congenital Glaucoma

Primary congenital glaucoma (PCG) is an autosomal-recessive condition characterized by high intraocular pressure (IOP), usually within the first year of life, which potentially could lead to optic nerve damage, globe enlargement, and permanent loss of vision. To date, PCG has been linked to three loci: 2p21 (GLC3A), for which the responsible gene is CYP1B1, and 1p36 (GLC3B) and 14q24 (GLC3C), for which the genes remain to be identified. Here we report that null mutations in LTBP2 cause PCG in four consanguineous families from Pakistan and in patients of Gypsy ethnicity. LTBP2 maps to chromosome 14q24.3 but is around 1.3 Mb proximal to the documented GLC3C locus. Therefore, it remains to be determined whether LTBP2 is the GLC3C gene or whether a second adjacent gene is also implicated in PCG. LTBP2 is the largest member of the latent transforming growth factor (TGF)-beta binding protein family, which are extracellular matrix proteins with multidomain structure. It has homology to fibrillins and may have roles in cell adhesion and as a structural component of microfibrils. We confirmed localization of LTBP2 in the anterior segment of the eye, at the ciliary body, and particularly the ciliary process. These findings reveal that LTBP2 is essential for normal development of the anterior chamber of the eye, where it may have a structural role in maintaining ciliary muscle tone.     

Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice

Cone-rod dystrophy (CRD) is an inherited progressive retinal dystrophy affecting the function of cone and rod photoreceptors. By autozygosity mapping, we identified null mutations in the ADAM metallopeptidase domain 9 (ADAM9) gene in four consanguineous families with recessively inherited early-onset CRD. We also found reduced photoreceptor responses in Adam9 knockout mice, previously reported to be asymptomatic. In 12-month-old knockout mice, photoreceptors appear normal, but the apical processes of the retinal pigment epithelium (RPE) cells are disorganized and contact between photoreceptor outer segments (POSs) and the RPE apical surface is compromised. In 20-month-old mice, there is clear evidence of progressive retinal degeneration with disorganized POS and thinning of the outer nuclear layer (ONL) in addition to the anomaly at the POS-RPE junction. RPE basal deposits and macrophages were also apparent in older mice. These findings therefore not only identify ADAM9 as a CRD gene but also identify a form of pathology wherein retinal disease first manifests at the POS-RPE junction.     

Eradications as reverse invasions: lessons from Pacific rat (Rattus exulans) removals on New Zealand islands

Eradications of kiore or Pacific rats (Rattus exulans) from islands around New Zealand have been followed by responses from resident species of coastal plants, invertebrates, reptiles and seabirds. These responses are compared with an invasion by ship rats (Rattus rattus), which devastated populations of invertebrates, birds and bats. Post-eradication responses only approximate the effects of invasions because recovery is limited to the residual pool of native species. Greater effects of kiore are indicated by adding incompatible species confined to rat-free locations. The extended list includes at least 15 species of invertebrates, two species of frogs, tuatara (Sphenodon punctatus), 11 species of lizards and 9 species of seabirds. The analyses indicate direct and indirect effects of kiore similar to those reported after ship rat invasions. This is despite indications from the literature that kiore are the least damaging of the three commensal rat species.     

Outcome of Tuberculosis Treatment in Patients with Diabetes Mellitus Treated in the Revised National Tuberculosis Control Programme in Malappuram District,Kerala, India

Settings

Kerala State, India has reported the greatest dual burden of Tuberculosis (TB) and Diabetes Mellitus (DM). Malappuram district in Kerala has monitored and recorded DM status and its control from 2010 under Revised National Tuberculosis Control Program (RNTCP).

Objectives

To assess, under programme conditions, comprehensiveness of recording DM status among TB cases and the TB treatment outcomes among DM patients (disaggregated by glycemic control) and compare with-non DM patients.

Design

This retrospective record review included 3,116TB patients from April 2010 to September 2011.DM was defined as per international guidelines and TB treatment outcomes were categorized as favourable(cured and treatment completed) and unfavourable(death, default, failure and transfer out). Relative Risk (RR) and 95% confidence intervals(CI) were calculated to assess the risk of unfavourable outcomes.

Results

DM status was recorded in 90% of TB cases and 667 (24%) had DM. 17% of DM patients and 23% of patients with unknown DM status had unfavourable outcomes but this difference was not statistically significant. Unadjusted RR for poor glycemic control or unknown control status for unfavourable outcome were (2.00; 95% CI 0.97–4.13) and (2.14; 95% CI 1.11–4.13).

Conclusion

This study could not confirm an adverse association between DM or its control during treatment and the course of response to TB treatment.DM screening in TB cases and recording of DM care needs to be improved to enable more conclusive evidence.     

Three new genera of Leptophlebiidae (Ephemeroptera) from New Zealand

Abstract

Three new genera—Austroclima, Mauiulus, and Cryophlebia—are established for species of Leptophlebiidae from New Zealand. The following new combinations are included: Austroclima sepia (Phillips) and Cryophlebia aucklandensis (Peters). Atalophlebioides sepia is redescribed as Austroclima sepia and a neotype is designated. Two new species, Austroclima jollyae and Mauiulus luma, are described. All life stages are described, and the relationships of each genus are discussed. Keys are given to male and female imagos, subimagos, and nymphs of each species, and to all New Zealand genera with species previously placed in Atalophlebioides.     

A revision of genus Atalophlebioides (Ephemeroptera: Leptophlebiidae)

Abstract

Atalophlebioides Phillips is redescribed as a monotypic genus endemic to New Zealand. All life stages of A. cromwelli (Phillips) are described, and a lectotype is designated. The relationships of the genus and the ecology of A. cromwelli are discussed.     

New genera and species of Leptophlebiidae (Ephemeroptera) from New Zealand

Abstract

New genera Isothraulus, Arachnocolus, and Penniketellus are established for three species of leptophlebiid mayfly from New Zealand. Each genus is monotypic and endemic to New Zealand. Isothraulus and Arachnocolus are known only from the northern North Island, and Penniketellus is known only from the Arthur's Pass area of the central South Island. The male and female imago, nymph, and egg of Isothraulus abditus n.sp., the male imago, male subimago, and nymph of Arachnocolus phillipsi n.sp., and the male and female imago, female subimago, and egg of Penniketellus insolitus n.sp. are described. The relationships of each genus and the ecology of nymphs of each species are discussed.     

Function of UreB in Klebsiella aerogenes urease

Urease from Klebsiella aerogenes is composed of three subunits (UreA-UreB-UreC) that assemble into a (UreABC)(3) quaternary structure. UreC harbors the dinuclear nickel active site, whereas the functions of UreA and UreB remain unknown. UreD and UreF accessory proteins previously were suggested to reposition UreB and increase the level of exposure of the nascent urease active site, thus facilitating metallocenter assembly. In this study, cells were engineered to separately produce (UreAC)(3) or UreB, and the purified proteins were characterized. Monomeric UreB spontaneously binds to the trimeric heterodimer of UreA and UreC to form (UreABC*)(3) apoprotein, as shown by gel filtration chromatography, integration of electrophoretic gel band intensities, and mass spectrometry. Similar to the authentic urease apoprotein, the active enzyme is produced by incubation of (UreABC*)(3) with Ni(2+) and bicarbonate. Conversely, UreBΔ1-19, lacking the 19-residue potential hinge and tether to UreC, does not form a complex with (UreAC)(3) and yields negligible levels of the active enzyme when incubated under activation conditions with (UreAC)(3). Comparison of activities and nickel contents for (UreAC)(3), (UreABC*)(3), and (UreABC)(3) samples treated with Ni(2+) and bicarbonate and then desalted indicates that UreB facilitates efficient incorporation of the metal into the active site and protects the bound metal from chelation. Amylose resin pull-down studies reveal that MBP-UreD (a fusion of maltose binding protein with UreD) forms complexes with (UreABC)(3), (UreAC)(3), and UreB in vivo, but not in vitro. By contrast, MBP-UreD does not form an in vivo complex with UreBΔ1-19. The soluble MBP-UreD-UreF-UreG complex binds in vitro to (UreABC)(3), but not to (UreAC)(3) or UreB. Together, these data demonstrate that UreB facilitates the interaction of urease with accessory proteins during metallocenter assembly, with the N-terminal hinge and tether region being specifically required for this process. In addition to its role in urease activation, UreB enhances the stability of UreC against proteolytic cleavage.