Selection of oral agents in the management of type 2 diabetes

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The effect of the introduction of a standard monitoring protocol on the investigations performed on the metabolic control of type 2 diabetes at Addington Hospital Medical Outpatients Department, Durban, South Africa

Background: A comprehensive approach to the control of type 2 diabetes is required to reduce mortality and morbidity. To improve diabetes management, in 2005 a protocol for the monitoring and management of type 2 diabetes, aligned to the 2003 Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) guidelines, was introduced atAddington Hospital Medical Outpatients Department, Durban, South Africa.Method: Data were collected from 120 randomly selected patients with type 2 diabetes. The number of glycated haemoglobin (HbA1c) and lipid estimations, blood pressure (BP) measurements and body mass indices (BMIs) recorded in 2005 was compared with those recorded in 2008 and 2009. The mean levels of these parameters and the number of patients reaching goal in 2008 were compared with the figures for 2009.Results: In 2005, 18.8% of patients had HbA1c levels measured compared with 82.9% in 2009 (P < 0.01). The mean HbA1c was 6.9% (± 1.9) in 2008 and 6.4% (± 2.0) in 2009 (P = 0.1). BP and BMI was measured in over 93% of patients in 2005, 2008 and 2009. BP goals were attained by 21% of patients in 2008 and 30% in 2009 (P = 0.65). The mean BMI in 2008was 29.4 kg/m2 (24% achieved goal), and in 2009 it was 28.6kg/m2 (29% achieved goal; P = 0.267). Lipid estimations rose significantly from 26% in 2005 to 73% in 2009 (P < 0.01). There was no improvement in the number of patients reaching target lipid levels between 2008 and 2009.Conclusion: The monitoring protocol improved adherence to the SEMDSA 2003 guidelines from 2005 to 2009. Overall glycaemic control was within target, but attainment of most nonglycaemic goals was suboptimal and did not improve over the study period

Prevalence of low serum testosterone levels among men with type 2 diabetes mellitus attending two outpatient diabetes clinics in KwaZulu-Natal Province, South Africa

Background. The reported prevalence of low testosterone among men with type 2 diabetes mellitus (T2DM) is high. However, there is a dearth of information on the prevalence of androgen deficiency symptoms and low serum testosterone levels in men with T2DM from sub-Saharan Africa. Scanty data are available from Nigeria, Ghana and South Africa (SA).Objectives. To determine the prevalence of low serum testosterone and associated risk factors and the prevalence of androgen deficiency symptoms in men with T2DM.Methods. In a cross-sectional observational study, androgen deficiency symptoms in men with T2DM attending two outpatient diabetes clinics in Durban, KwaZulu-Natal Province, SA, were assessed using the Ageing Males’ Symptoms Scale (AMS) questionnaire and direct enquiry. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), luteinising hormone (LH), fructosamine, serum lipids and glycated haemoglobin (HbA1c) were measured and free testosterone (FT) was calculated. TT, SHBG and FT levels were measured in control subjects with no history of diabetes.Results. There were 148 men with T2DM in the study group and 50 control subjects in the control group. In the study group, the majority were black Africans (58.8%); Indians (39.2%) and whites (2.0%) constituted the remainder. The mean (standard deviation (SD)) age was 57.5 (11.2) years, the mean duration of diabetes 11.4 (8.9) years and the mean HbA1c 8.6% (1.9%). Of the study group, 85.8% had metabolic syndrome. Mean TT, SHBG and FT and median LH (interquartile range) in the study group were within normal ranges. However, mean (SD) serum TT and FT were lower in the study group than in the control subjects (14.5 (5.8) v. 18.8 (7.2) nmol/L; p<0.001 and 265.9 (90.4) v. 351.7 (127.3) pmol/L; p<0.001, respectively). The prevalence of low serum total testosterone (LSTT) and low serum free testosterone (LSFT) in the study group was 35.8% and 16.2%, respectively. The prevalence of androgen deficiency symptoms using the AMS questionnaire was 74.5% and correlated poorly with LSTT or LSFT. In multivariate analysis, LSFT was significantly associated with age (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.02 - 1.218; p=0.043) and waist circumference (WC) (OR 1.033, 95% CI 0.999 - 1.068; p=0.059). LSTT was associated with body mass index (BMI) only (OR 1.138, 95% CI 1.063 - 1.218; p<0.0001). TT correlated inversely with BMI, WC and the number of metabolic syndrome criteria. FT correlated inversely with BMI, WC and WHR.Conclusions. There was a high prevalence of LSTT, LSFT and androgen deficiency symptoms in this study. Serum TT and FT were lower in men with T2DM than in control subjects. Risk factors associated with LSFT or LSTT included higher BMI and WC and older age. The AMS score was a poor predictor of low testosterone. More research is required locally before any screening policy can be recommended.

A virus-inactivating system from tobacco leaves

SUMMARY: Purified preparations of the Rothamsted tobacco necrosis virus made by sedimenting the virus from freshly expressed sap lose infectivity slowly at O6 and rapidly at 18°. Stable infective preparations can be made by ultracentrifugation provided the sap is first frozen or allowed to age; unstable preparations can be stabilized by prolonged centrifugation at 8000 g, or by incubation with citrate and azide. Stable virus preparations lose their infectivity when exposed to the material that sediments from leaf sap centrifuged at 4000–8000 g. This inactivation demands air and is prevented by the presence of azide, but when the sedimented material is kept in air at 0° for some hours a low-molecular weight substance separates from it. and this inactivates the virus whether or not air or azide are present. The material sedimented from the sap of uninfected tobacco leaves, or leaves infected with tobacco mosaic virus, inactivates virus less readily than does material from leaves infected with tobacco necrosis or tobacco ringspot virus. The sediments inactivate tobaceo ringspot but not tobacco mosaic virus. The nature of the inactivating substance made by the sediments is unknown, but aldehydes and derivatives of ascorbic acid have comparable effects. Inactivated virus preparations are still serologically active and resemble active ones in all other properties studied

Some factors affecting the activation of virus preparations made from tobacco leaves infected with a tobacco necrosis virus

SUMMARY: Preparations of the Rothamsted tobacco necrosis virus were made by the ultracentrifugation of sap from infected tobacco leaves after a preliminary concentration by freezing. Not all the anomalous nucleoprotein in these preparations was infective, and the products were fractionated by differential ultracentrifugation at lower speeds and by precipitation at pH 4 in the presence of sedimentable protein from uninfected leaves. The more readily sedimentable and precipitable material carried with it most infectivity, whereas the other material had the greater sero-logical activity. Preparations made quickly from freshly expressed sap were less infective than those made from sap that had been frozen or allowed to age for a few days. The extent of the activation produced by these treatments depended on the physiological condition of the infected leaves. As much virus could be extracted from the leaf residues as occurred in the sap. The infectivity of this residual virus depended on the medium used for its extraction. It is suggested that much of the infectivity of this virus in sap is acquired during or after extraction from the leaf, but the relationship between the particles with different sizes and properties remains uncertain

Activity of fragmented and reassembled tobacco mosaic virus

SUMMARY: Studies of the products obtained when tobacco Mosaic virus (TMV) is disrupted with alkali or phenol suggest that immunological specificity is primarily an attribute of the protein and infectivity of the nucleic acid. Although exposing the much of the nucleoprotein sedimented when preparations are ultracentrifuged at pH 6 is not infective. The unsedimented protein fragments are inhibitors of infection; from such unsedimentable material, which at 5 g./l. produced no lesion when inoculated to Nicotiana glutinosa, some infective nucleoprotein could sometimes be separated by precipitation with ammonium sulphate, followed by ultracentrifugation. The infectivity of fragmented TMV is ephemeral, but it is stabilized when the fragments are reunited. Nucleic acid preparations made by phenol are quickly inactivated by ribonucleases from pancreas or leaves; pancreatic ribonuclease also inactivates alkali-made fragments, but the infectivity of these is stabilized by leaf ribonuclease. Phenol-made preparations are much less infective per unit of phosphorus than intact TMV, but measurements of the relative infectivities of two kinds of inocula are complicated because the two respond differently to dilution and they are not equally able to infect N, glutinosa leaves in differently to dilution and Although urea does not inactivate phenol-made preparations, physilogical states, exposing TMV to urea has little or no infectivity. The possibility that infective TMV can be reassembled in vitro from previously non-infective components cannot be excluded, but all the results that could be interpreted as suggesting this are also interpretable in other ways, either by the removal of inhibitions of infection or by the stabilization of infective fragments that otherwise would have become inactive before testing. &nbsp

Observations on the anomalous proteins occurring in extracts from plant infected with strains of tobacco mosaic virus

When extracts from plants infected with various strains of tobacco mosaic virus were ultracentrifuged, the non-infective supernatant fluids still contained 0·5-5% of the protein serologically related to the viruses. The small, mostly spherical, particles aggregated to form short rods as the antigen was progressively purified by precipitation with acid or salts. It formed long rods when heated in pH 5·5 buffer or when incubated with trypsin. As the particles increased in length, their serological behaviour in precipitation tests changed from ‘somatic’ to ‘flagellar’ type. Purified preparations of the unsedimented antigen from plants infected with either of two virus strains contained 0·1-0·2% phosphorus, seemingly in the form of a ribose nucleic acid. No evidence was obtained that the preparations were mixtures containing some particles with the 0·5% phosphorus characteristic of infective virus and some particles of protein free from nucleic acid. One virus strain produced a higher ratio than the others of unsedimented to sedimented antigen. The amount of unsedimented antigen was correlated with the total content of anomalous protein when the protein was increasing rapidly, but later it fluctuated unpredictably. No conditions were found that consistently favoured its accumulation, but when plants systemically infected with the type strain were kept at 36°, the total amount of antigen decreased, while the amount unsedimented sometimes increased. The proportion of the total antigen now obtained as poorly infective nucleoprotein is much less than 10 years ago, when a third of it sedimented in the ultracentrifuge but failed to compact into a pellet. Now the uncompacted sediment, with all the host plants and virus strains used, contains only a trivial part of the total antigen. The virus released into sap when leaves are minced is, weight for weight, more infective than the virus that remains in the leaf residues until it is released by fine grinding

The infectivity and inactivation of nucleic acid preparations from tobacco mosaic virus

The infectivity of nucleic acid preparations made by disrupting tobacco mosaic virus with phenol was increased, relative to that of intact virus, by keeping test plants in darkness or at 37° for some time before they were inoculated. The differences in susceptibility to infection of leaves in different physiological states was too great to be explained by differences in the ability of leaf extracts to inactivate nucleic acid preparations in vitro. The spontaneous inactivation of the preparations in vitro was not prevented by inhibitors of ribonucleases and most additions to the preparations increased the rate of inactivation. Not all the inactivations are readily explicable on the assumption that the minimal infective unit is a pure nucleic acid built up solely from nucleotides. Leaf sap and saliva are reasonably assumed to inactivate because they contain ribonuclease; also, inactivations by formaldehyde phenylglyoxal, and thiaminase in the presence of thiamine, may well reflect reactions with known components of nucleic acids. However, it is less easy to invoke such actions to explain the inactivation by spermine, ‘interferon’, some oxidizing agents, leaf mitochondria in the presence of some other substances, and the greater rate of inactivation in vacuo than in air. Although nucleic acid seems essential for infectivity, it seems prudent to suspend judgement about the precise chemical identity of the minimal infective unit