Socio-Demographic and Clinical Differences in Subjects with Tuberculosis with and without Diabetes Mellitus in Brazil – A Multivariate Analysis

Background

Several studies have evaluated the relationship between diabetes mellitus (DM) and tuberculosis (TB), but the nature of this relationship is not fully understood. TB incidence may be influenced by immunosuppression from DM, but this association may be confounded by other clinical and socioeconomic factors. We aimed to assess socio-demographic and clinical differences in TB patients with and without DM.

Methods

Using the Brazilian national surveillance system (SINAN), we compared 1,797 subjects with TB and DM with 29,275 subjects diagnosed with TB only in 2009. We performed multivariate analysis to identify factors associated with the presence of DM among TB patients.

Results

Subjects with TB – DM were older; have initial positive sputum smear test (OR = 1.42, 95% CI 1.26–1.60), and were more likely to die from TB (OR = 1.44, 95% CI 1.03–2.01). They were less likely to have been institutionalized [in prison, shelter, orphanage, psychiatric hospital (OR = 0.74, 95% CI 0.60–0.93)]; developed extra pulmonary TB (OR = 0.62, 95% CI 0.51–0.75) and to return to TB treatment after abandonment (OR = 0.66, 95% CI 0.51–0.86).

Conclusions

Prevalence of NCD continues to rise in developing countries, especially with the rise of elderly population, the prevention and treatment of infectious diseases will be urgent. DM and TB represent a critical intersection between communicable and non-communicable diseases in these countries and the effect of DM on TB incidence and outcomes provide numerous opportunities for collaboration and management of these complex diseases in the national public health programs.     

INTRACELLULAR DISTRIBUTION OF CALCIUM IN DEVELOPING BREAST MUSCLE OF NORMAL AND DYSTROPHIC CHICKENS

To follow the intracellular distribution of calcium in the breast muscles of developing chickens, Ca⁴⁵ was injected into the albumen of predeveloped eggs. Since the embryos were grown in a radioactive medium, a complete exchange of the isotope for its non-radioactive counterpart in muscles was accomplished. Subcellular particulates of the muscle cells were separated by the method of differential centrifugation. Analysis of the separated fractions showed that in the muscles of the 13-day embryo, when the nuclear-myofibrillar ratio is high, 65 per cent of the muscle calcium is in the nuclei. With the increased synthesis of myofibrils, the nuclear-myofibrillar ratio decreases with a concomitant fall in radioactivity. Thus, calcium was not associated with the developing myofibrils. At the time of hatching, when myofibrils perform physiological work, the highest level of calcium is in the mitochondria. This suggests that the mitochondria play a key role in the physiological activities of calcium in the cell. The microsomal fraction reaches a maximal level of calcium when the adult composition of muscle is attained. Results of investigations on dystrophic muscles show changes in the calcium distribution of the fractions as early as the 3rd week of embryonic development, which are interpreted to indicate an alteration in the protein metabolism of the cell, or an early destruction of muscle tissue. Further, alterations in the calcium content of fractions which seem to regulate the movements of this ion in the cell are discussed. A new technique for homogenizing tissues from embryos of different ages is presented.     

Synthesis of Replicative Form Deoxyribonucleic Acid and Messenger Ribonucleic Acid by Gene IV Mutants of Bacteriophage S13

Gene IV mutants of bacteriophage S13 are known to be blocked in infectious replicative form (RF) DNA synthesis, producing only a small fraction of the RF formed by wild-type phage. This investigation shows that gene IV mutants form only parental RF and are blocked in the synthesis of any progeny RF, either infectious or noninfectious. This was determined by density labeling of RF in cells treated with mitomycin C to suppress host deoxyribonucleic acid (DNA) synthesis. RF synthesis was also studied in untreated cells, using methylated albumin columns to separate RF from host DNA. In this case it was also found that synthesis of progeny RF by gene IV mutants is negligible. It has been found by DNA-ribonucleic acid (RNA) hybridization experiments that gene IV mutants form at least as much or more messenger RNA than wild-type phage. Therefore, parental RF alone can form messenger RNA in appreciable amounts.     

3-Alkynyl selenophene protects against carbon-tetrachloride-induced and 2-nitropropane-induced hepatic damage in rats

The aim of this study was to investigate the protective effect of 3-alkynyl selenophene (3-ASP) on acute liver injury induced by carbon tetrachloride (CCl₄) and 2-nitropropane (2-NP) in rats. On the first day of treatment, the animals received 3-ASP (25 mg/kg, p.o.). On the second day, the rats received CCl₄ (1 mg/kg, i.p.) or 2-NP (100 mg/kg, p.o.). Twenty-four hours after CCl₄ or 2-NP administration, the animals were euthanized, and their plasma and liver were removed for biochemical and histological analyses. The histological analysis revealed extensive injury in the liver of CCl₄-exposed and 2-NP-exposed rats, which was attenuated by 3-ASP. 3-ASP significantly attenuated (1) the increase in plasmatic aspartate and alanine aminotransferase activities and lipid peroxidation levels induced by CCl₄ and 2-NP; (2) the inhibition of δ-aminolevulinic dehydratase activity caused by 2-NP; and (3) the decrease in ascorbic acid (AA) levels and catalase (CAT) activity caused by CCl₄. AA levels and CAT activity remained unaltered in the liver of rats exposed to 2-NP. The protective effect of 3-ASP on acute liver injury induced by CCl₄ and 2-NP in rats was demonstrated.     

Cdk-counteracting phosphatases unlock mitotic exit

Entry into mitosis of the eukaryotic cell cycle is driven by rising cyclin-dependent kinase (Cdk) activity. During exit from mitosis, Cdk activity must again decline. Cdk downregulation by itself, however, is not able to guide mitotic exit, if not a phosphatase reverses mitotic Cdk phosphorylation events. In budding yeast, this role is played by the Cdc14 phosphatase. We are gaining an increasingly detailed picture of its regulation during anaphase, and of the way it orchestrates ordered progression through mitosis. Much less is known about protein dephosphorylation during mitotic exit in organisms other than budding yeast, but evidence is now mounting for crucial contributions of regulated phosphatases also in metazoan cells.     

Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast

After anaphase, the high mitotic cyclin-dependent kinase (Cdk) activity is downregulated to promote exit from mitosis. To this end, in the budding yeast S. cerevisiae, the Cdk counteracting phosphatase Cdc14 is activated. In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1. During anaphase, Cdk- and Polo-dependent phosphorylation of Net1 is thought to release active Cdc14. How Net1 is phosphorylated specifically in anaphase, when mitotic kinase activity starts to decline, has remained unexplained. Here, we show that PP2A(Cdc55) phosphatase keeps Net1 underphosphorylated in metaphase. The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and downregulates PP2A(Cdc55), thereby facilitating Cdk-dependent Net1 phosphorylation. PP2A(Cdc55) downregulation also promotes phosphorylation of Bfa1, contributing to activation of the "mitotic exit network" that sustains Cdc14 as Cdk activity declines. These findings allow us to present a new quantitative model for mitotic exit in budding yeast.