Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy

Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy. To determine the effect of chronic exercise training on renal function in animals with moderate renal insufficiency, rats with 75% renal ablation were either exercise trained by swimming for two months or remained sedentary. Glomerular filtration rate was significantly higher in trained (1.89 ± 0.07 ml/min) than in sedentary rats (1.52 ± 0.11 ml/min). No change was observed in renal blood flow or the degree of hypertension. Proteinuria was reduced in trained (13.6 ± 4.9 mg/24 hr) compared to sedentary animals (33.5 ± 9.2 mg/24 hr). The degree of glomerulosclerosis was much less prominent in trained animals. Plasma, low-density lipoprotein cholesterol-levels and total triglycerides were reduced in trained compared to sedentary rats. This study suggests that chronic exercise training ameliorates the progression of renal disease and improves plasma lipids in rats with moderate renal insufficiency. The mechanism for this improvement in renal function appears to be independent of the influence of systemic blood pressure

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

On Asymmetric Collisions with Large Disruption Parameters

Collisions between a weak electron bunch and a strong positron bunch are studied within a flat beam model. Electrons are tracked through the transverse space charge field of the positron bunch, and it is shown that positrons in a storage ring may remain stable after asymmetric collisions with a weak electron bunch in spite of large values of the electron disruption parameter. The plasma oscillations that effect collisions with large disruption parameters may be suppressed by properly matching the electrons

Tumor Necrosis Factor Alpha Stimulates Killing of Mycobacterium tuberculosis by Human Neutrophils

The ability of human neutrophils to aid in defense against pulmonary infection with Mycobacterium tuberculosis is controversial. In this study, we have shown that neutrophils respond to and phagocytose M. tuberculosis in human lesions. Neutrophils from healthy individuals were able to kill significant fractions of an inoculum of M. tuberculosis within 1 h of phagocytosis, and this ability was enhanced by tumor necrosis factor alpha but not by gamma interferon. The mycobactericidal mechanism was nonoxidative, as inhibitors of reactive oxygen or reactive nitrogen intermediates did not interfere with killing. However, the mycobactericidal mechanism was associated with increased exposure of intracellular M. tuberculosis to neutrophil defensins. In vitro, human neutrophil peptides 1 to 3 were not able to kill the bacilli even at much higher levels. These studies support the concept that human neutrophils are directly involved in defense against infection with M. tuberculosis

The Potential Advantages of Nanoparticle Drug Delivery Systems in Chemotherapy of Tuberculosis

Nanoparticle-based drug delivery systems have considerable potential for treatment of tuberculosis (TB). The important technological advantages of nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation. Nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix. These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency, and may resolve the problem of nonadherence to prescribed therapy, which is one of the major obstacles in the control of TB epidemics. This article highlights some of the issues of nanotechnology relevant to the anti-TB drugs

Renal Siderosis in Donor Allograft: Pathologic and Clinical Sequelae.

Transplantation of a cadaver kidney with marked siderosis and its outcome has not been reported. Increasing use of marginal kidneys has become common practice to expand the donor pool to meet the growing demand and will lead to increased recognition of kidney disease in cadaver donors with an unknown effect on graft outcome. This is a case report of a recipient of a cadaver kidney with marked siderosis monitored by surveillance biopsies and evaluated by clinico-pathological correlation. The recipient continued to have transplant kidney function, and a surveillance biopsy shows the natural course of the pathologic resolution of renal siderosis