Tricyclic antidepressives - A possible mode of action

No Abstract

The dormant blood microbiome in chronic, inflammatory diseases

Blood in healthy organisms is seen as a ‘sterile’ environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. ‘Non-culturability’, reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as ‘dysbiosis’). Another source is microbes translocated from the oral cavity. ‘Dysbiosis’ is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term ‘atopobiosis’ for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines.Biotechnology and Biological Sciences Research Council (grant BB/L025752/1) as well as the National Research Foundation (NRF) of South Africa.http://femsre.oxfordjournals.orghb201

Latitudinal gradients of galactic cosmic rays during the 2007 solar minimum

Ulysses, launched in 1990 October in the maximum phase of solar cycle 22, completed its third out-of-ecliptic orbit in 2008 February. This provides a unique opportunity to study the propagation of cosmic rays over a wide range of heliographic latitudes during different levels of solar activity and different polarities in the inner heliosphere. Comparison of the first and second fast latitude scans from 1994 to 1995 and from 2000 to 2001 confirmed the expectation of positive latitudinal gradients at solar minimum versus an isotropic Galactic cosmic ray distribution at solar maximum. During the second scan in mid-2000, the solar magnetic field reversed its global polarity. From 2007 to 2008, Ulysses made its third fast latitude scan during the declining phase of solar cycle 23. Therefore, the solar activity is comparable in 2007-2008 to that from 1994 to 1995, but the magnetic polarity is opposite. Thus, one would expect to compare positive with negative latitudinal gradients during these two periods for protons and electrons, respectively. In contrast, our analysis of data from the Kiel Electron Telescope aboard Ulysses results in no significant latitudinal gradients for protons. However, the electrons show, as expected, a positive latitudinal gradient of ~0.2% per degree. Although our result is surprising, the nearly isotropic distribution of protons in 2007-2008 is consistent with an isotropic distribution of electrons from 1994 to 1995

Modelling cosmic ray intensities along the Ulysses trajectory

Time dependent cosmic ray modulation in the inner heliosphere is studied by comparing results from a 2-D, time-dependent cosmic ray transport model with Ulysses observations. A compound approach, which combines the effects of the global changes in the heliospheric magnetic field magnitude with drifts to establish a realistic time-dependence, in the diffusion and drift coefficients, are used. We show that this model results in realistic cosmic ray modulation from the Ulysses launch (1990) until recently (2004) when compared to 2.5-GV electron and proton and 1.2-GV electron and Helium observations from this spacecraft. This approach is also applied to compute radial gradients present in 2.5-GV cosmic ray electron and protons in the inner heliosphere. The observed latitude dependence for both positive and negative charged particles during both the fast latitude scan periods, corresponding to different solar activity conditions, could also be realistically computed. For this an additional reduction in particle drifts (compared to diffusion) toward solar maximum is needed. This results in a realistic charge-sign dependent modulation at solar maximum and the model is also applied to predict charge-sign dependent modulation up to the next expected solar minimum

Attempts to transmit Anaplasma marginale with Hippobosca rufipes and Stomoxys calcitrans

Three attempts to transmit anaplasmosis with field collections of Hippobosca rufipes were unsuccessful, despite the fact that the flies had been fed initially on splenectomized cattle acutely infected with Anaplasma marginale. However, 1 out of the 3 attempts, made concurrently with the others, to transmit this organism with Stomoxys calcitrans was successful. The prepatent period was 27 days.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Humalog Mix25 improves 24-hour plasma glucose profiles compared with the human insulin mixture 30/70 in patients with type 2 diabetes mellitus

Objective. To compare the effects of Humalog Mix25 (Humalog Mix75/25 in the USA) (Mix25) and human insulin 30/70 (30/70) on the 24-hour inpatient plasma glucose (PG) profile in patients with type 2 diabetes mellitus (T2DM). Design. A randomised, open-label, 8-week crossover study. Study insulins were injected twice daily, 5 minutes before breakfast and dinner. Setting. Four-week outpatient (dose-adjustment) treatment phase, and 3-day inpatient (test) phase. Patients. Twenty-five insulin-treated patients with T2DM (ages 40 - 66 years), mean (± standard error of the mean) (SEM) HbA1c 7.7% ± 0.23%, and body mass index (BMI) 29.3 ± 0.83 kg/m2. Outcome measures. 24-hour PG profiles, PG excursions after meals, PG area under the curve (AUC), and 30-day hypoglycaemia rate. Results. The 2-hour PG excursions following breakfast (5.5 ± 0.34 v. 7.2 ± 0.34 mmol/l, p = 0.002) and dinner (2.4 ± 0.27 v. 3.4 ± 0.27 mmol/l, p = 0.018) were smaller with Mix25 than with 30/70. PG AUC between breakfast and lunch was smaller with Mix25 than with 30/70 (77.6 ± 3.8 v. 89.5 ± 4.3 mmol/h/ml, p = 0.001). PG AUC between lunch and dinner, dinner and bedtime, and bedtime and breakfast did not differ between treatments. Pre-meal and nocturnal PG were comparable. The postprandial insulin requirement for lunch meals was supplied equally by the two insulin treatments. The thirty-day hypoglycaemia rate was low (Mix25 0.049 ± 0.018 v. 30/70 0.100 ± 0.018 episodes/patient/30 days, p = 0.586) for both treatments. Conclusion. In patients with T2DM, Mix25 improved the 24-hour PG profile with lower postprandial PG excursions than with human insulin 30/70. (South African Medical Journal: 2003 93(3): 219-223