Fibrosis human studies

To reduce mortality, administration of an aldosterone antagonist, either eplerenone or spironolactone, should be considered within the first 2 weeks following MI in all patients who are already receiving an ACE inhibitor (or ARB) and have an EF of equal to or less than 40% and either heart failure symptoms or diagnosis of diabetes mellitus.3 Aldosterone plays an important role in heart failure and in MI because it promotes vascular and myocardial fibrosis, endothelial dysfunction, hypertension, left ventricular hypertrophy, sodium retention, potassium and magnesium loss, and arrhythmias. Aldosterone antagonists have been shown in experimental and human studies to attenuate these adverse effects.70 Spironolactone decreases all-cause mortality in patients with stable, severe heart failure.71... 

Madri, J. A., and H. Furthmayr (1980). Collagen polymorphism in the lung an immunohemical study of pulmonary fibrosis. Human Pathol. 11 353-366. 

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

No studies were located on the effects of cyanide on the adrenal gland in humans. However, effects on the adrenal gland, including swelling, hemorrhage, and fibrosis, were observed in dogs fed cassava, as well as in dogs fed rice with sodium cyanide added (Kamalu 1993). 

Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans after inhalation exposure to bromomethane, but several studies in mice and rats indicate that the heart is susceptible to injury. Effects which have been reported at exposure levels of 90-160 ppm include cardiomyopathy (Eustis et al. 1988), myocardial degeneration and cardiac thrombi (Reuzel et al. 1987) and fibrosis (Kato et al. 1988). 

Other Systemic Effects. Adrenal fibrosis with lipid accumulation was reported in one study in mice, but these effects have not been observed in humans known to be exposed to heptachlor and have not been verified in other species. There has been no measurement of adrenal hormone in exposed humans or animals. Body weight changes have, in general, been accompanied by a decrease in food consumption, due possibly to taste aversion. 

In addition to other models [153], tubulointerstitial inflammation and fibrosis can be obtained by ureter obstruction. The inflammation develops very rapidly and is severe. The model is a good reflection of ureter obstruction in humans. However, a serious drawback in using this model for tubular drug delivery studies is the fact that glomerular filtration is absent. 

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