Osmolar effect

Production of urine of varying concentrations. In order to regulate plasma volume and osmolarity effectively, the kidneys must be able to alter the volume and concentration of the urine that is eliminated. Accordingly, the concentration of urine may be varied over a very wide range depending upon the body s level of hydration. The most dilute urine produced by the kidneys is 65 to 70 mOsm/1 (when the body is overhydrated) and the most concentrated urine is 1200 mOsm/1 (when the body is dehydrated). (Recall that plasma osmolarity is 290 to 300 mOsm/1.)... 

Osmolar effects lead to cell lysis as we can demonstrate in epithelial (ARPE19) and mesenchymal... 

DNA damage (UDS) (3 tests selected that are acceptable by regulatory authorities) (w+ only at high doses possible pH or osmolarity effect) ... 

Vasopressin is a peptide hormone produced by the hypothalamus and secreted by the posterior pituitary in response to stimulation. Normal stimuli for vasopressin release are hyperosmolarity and hypovolemia, with thresholds for secretion of greater than 280 mOsm/kg and greater than 20% plasma volume depletion. A number of other stimuli, such as pain, nausea, epinephrine, and numerous drugs, induce release of vasopressin. Vasopressin release is inhibited by volume expansion, ethanol, and norepinephrine. The physiological effect of vasopressin is to promote free water clearence by altering the permeability of the renal collecting duct to water. In addition, it has a direct vasoconstrictor effect. Consequently, vasopressin results in water retention and volume restoration. In patients with septic shock, vasopressin is appropriately secreted in response to hypovolemia and to elevated serum osmolarity (R14). 

Antidiuretic hormone promotes the reabsorption of water from the tubules of the kidney, or antidiuresis. Specifically, it acts on the collecting ducts and increases the number of water channels, which increases the diffusion coefficient for water. This results in the body s conservation of water and the production of a low volume of concentrated urine. The reabsorbed water affects plasma osmolarity and blood volume. This effect of ADH on the kidney occurs at relatively low concentrations. At higher concentrations, ADH causes constriction of arterioles, which serves to increase blood pressure. Antidiuretic hormone secretion is regulated by several factors ... 

Diuretics are drugs that cause an increase in urine output. It is important to note that, except for the osmotic diuretics, these drugs typically enhance the excretion of solute and water. Therefore, the net effect of most diuretics is to decrease plasma volume, but cause little change in plasma osmolarity. Five classes of diuretics and their major sites of action are ... 

Osmotic diuretics such as mannitol act on the proximal tubule and, in particular, the descending limb of the Loop of Henle — portions of the tubule permeable to water. These drugs are freely filtered at the glomerulus, but not reabsorbed therefore, the drug remains in the tubular filtrate, increasing the osmolarity of this fluid. This increase in osmolarity keeps the water within the tubule, causing water diuresis. Because they primarily affect water and not sodium, the net effect is a reduction in total body water content more than cation content. Osmotic diuretics are poorly absorbed and must be administered intravenously. These drugs may be used to treat patients in acute renal failure and with dialysis disequilibrium syndrome. The latter disorder is caused by the excessively rapid removal of solutes from the extracellular fluid by hemodialysis. 

The osmoreceptors of the hypothalamus monitor the osmolarity of extracellular fluid. These receptors are stimulated primarily by an increase in plasma osmolarity they then provide excitatory inputs to the thirst center and the ADH-secreting cells in the hypothalamus. The stimulation of the thirst center leads to increased fluid intake. The stimulation of the ADH-secreting cells leads to release of ADH from the neurohypophysis and, ultimately, an increase in reabsorption of water from the kidneys and a decrease in urine output. These effects increase the water content of the body and dilute the plasma back toward normal. Plasma osmolarity is the major stimulus for thirst and ADH secretion two additional stimuli include ... 

Modifying the properties of plant culture media, including increasing the osmolarity, reducing the effective concentration of selected heavy metals and altering the pH, has resulted in enhanced foreign protein accumulation or stability in some systems. 

The answer is c (HardmanT pp 695-697.) Mannitol increases serum osmolarity and therefore pulls water out of cells, cerebrospinal fluid (C5F), and aqueous humor. This effect can be useful in the treatment of elevated intraocular or intracranial pressure. However, by expanding the intravascular volume, mannitol can exacerbate CHF... 

The fed and fasted state may also have significant effects on the absorption or solubility of a compound. Compositions of media that simulate the fed and fasted states can be found in the literature (19) (see also Chapter 5). These media reflect changes in the pH, bile concentrations, and osmolarity after meal intake and therefore have a different composition than that of typical compendial media. They are primarily used to establish in vitro-in vivo correlations during formulation development and to assess potential food effects and are not intended for quality control purposes. For quality control purposes, the substitution of natural surfactants (bile components) with appropriate synthetic surfactants is permitted and encouraged because of the expense of the natural substances and the labor-intensive preparation of the biorelevant media. 

Osmolarity of perfusate solution The buffer osmolarity should be standardised to facilitate estimation of Peff values. Generally adjusted to physiological conditions of 290 mOsm/kg. (70 mM phosphate buffer) with 5.4 mM potassium chloride, 48 mM sodium chloride, 35 mM mannitol, and 10 mM D-glucose. Lane et al. [131] demonstrated the effect of hypersomolar perfusion on Tapp of ibuprofen in the in situ rat gut technique. Hypersomolar solutions tended to decrease Peff values, attributable to a reversed solvent drag effect. 

While there are limitations associated with the use of an in vitro permeability model for assessing the transport of compounds across the buccal mucosa, it can still be useful in assessing and comparing the permeability of compounds under different conditions, such as pH, temperature, and osmolarity, which provide valuable information on the mechanisms involved in drug transport. Additionally, the preliminary effects of potential chemical penetration enhancers or formulation excipients may be assessed, and these may provide a substantial rationale for subsequently assessing the effect of these agents in man. 

Cidal effects can be a result of the disruption of the cell wall or membrane. Cell lysis may occur when water diffuses into the high-osmolarity bacterial cytosol through the antibiotic-induced holes in the membrane, causing the bacteria to swell and burst. Cidal effects also can occur as a consequence of inhibition of bacterial DNA replication or transcription. 

A toxicity that is unique to cyclophosphamide and ifosfamide is cystitis. Dysuria and decreased urinary frequency are the most common symptoms. Rarely, fibrosis and a permanently decreased bladder capacity may ensue. The risk of development of carcinoma of the bladder also is increased. Large intravenous doses have resulted in impairment of renal water excretion, hyponatremia, and increased urine osmolarity and have been associated with hemorrhagic subendocardial necrosis, arrhythmias, and congestive heart failure. Interstitial pulmonary fibrosis may also result from chronic treatment. Other effects of chronic drug treatment include infertility, amenorrhea, and possible mutagenesis and carcinogenesis. 

In the situation where the effect of filtration - that is, water movement across the membrane due to the difference in hydrostatic pressure and/or osmolarity - can be neglected, the overall resistance for mass transfer in hemodialyzers with flat membranes is given as... 

Osmolarity is the physical result of the dissociation of substances in fluids. It can be measured by freeze point depression. The effects of osmolar changes are mostly seen on sanipermeable manbranes as known from almost aU manbranes of living tissues. The known effects on erythrocytes such as the formation of blown-up sphero-cytes in hypoosmolar conditions and shrinkage in hyperosmolar conditions are transferable to aU other cells. 

To have insight into these mechanisms, we have performed and published several experiments on diffusion of corrosive, rinsing with different osmolar solutions to check the influence of osmolar conditioning of the cornea [8]. Further, we have tried to evaluate the diffusion of corrosive throughout the cornea [9]. In the latest experiments being published under www.acto.de, we present the effect of fluids of different osmolarities and their action on cells. Unpublished data give insight into... 

The effects of osmolarity on cells are well known from physiology. Semipermeable membranes allow a water flux depending on the number of solved ions. Therefore, a cell with its own tissue osmolarity of about... 

Higher osmolarities in early rinsing have effect on the integrity of cells and stabilize the cellular bodies against the water influx. This concept is realized by Diphoterine of 820 mOsmol. 

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