Proteins excreted

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers decrease protein excretion and are the drugs of choice for hypertension in patients with CKD. 

The presence of protein in the urine is a marker of glomerular and tubular dysfunction and is recognized as an independent risk factor for the progression of CKD.8 Furthermore, the degree of proteinuria correlates with the risk for progression of CKD. An increase of 1 g of protein excretion per day is associated with a five-fold increase in the risk of progression of CKD, regardless of the cause of CKD.9 The mechanisms by which proteinuria potentiates CKD are discussed later. Microalbuminuria is also linked with vascular injury and increased cardiovascular mortality.10... 

The primary marker of structural kidney damage is proteinuria, even in patients with normal GFR. Clinically significant proteinuria is defined as urinary protein excretion greater than 300 mg/day or greater than 20 mcg/minute in a timed urine collection. Significant proteinuria can also be determined by a spot urine dipstick greater than 30 mg/dL or... 

The nondihydropyridine calcium channel blockers have been shown to also decrease protein excretion in patients with diabetes,20 but the reduction in proteinuria appears to be related to the reductions in blood pressure. The maximal effect of nondihydropyridine calcium channel blockers on proteinuria is seen with a blood pressure reduction to less than 130/80 mm Hg and no additional benefit is seen with increased doses. Dihydropyridine calcium channel blockers, however, do not have the same effects on protein excretion, and may actually worsen protein excretion.17... 

Proteinuria Abnormally high amount of protein in the urine. Proteinuria is defined as urinary protein excretion of greater than 150 mg per day. 

Foster, N. and Lee, D.L. (1996) A vasoactive intestinal polypeptide-like protein excreted/secreted by Nippostrongylus brasiliensis and its effect on contraction of uninfected rat intestine. Parasitology 112, 97-104. 

Male rats are sensitive to renal tubular nephropathy after exposure to hexachloroethane. The lesions observed are characteristic of hyaline droplet nephropathy. They are most likely the result of hexachloroethane or one of its metabolites binding to the excretory protein 2p-globulin, altering its kidney transport, and leading to the formation of hyaline droplets. This protein is synthesized by male rats and accounts for 26% of their urinary protein excretion (Olson et al. 1990). It is not excreted in female rats except in minimal quantities. Since some effects are also seen in kidneys of female rats and in male and female mice that do not synthesize 2p-globulin, hexachloroethane must also have milder adverse effects on the kidney through a different mechanism. 

Aminoaciduria, proteinuria and morphological kidney lesions can be induced in rats with a single [420] dose of NiCl2 (2-5 mg Ni/kg intraperitoneally). Amino-acid protein excretions consistently returned to normal by day 5 after exposure. 

As angiotensin-converting enzyme inhibitors influence protein excretion in renal disease, Gansevoort et al. (G2) and Keilani et al. (K10) investigated serum Lp(a) concentrations in patients treated with Lisinopril resp. fosinopril and detected a reduction. 

Angiotensin-converting enzyme (ACE) inhibitors such as captopril exert a long-term reno-protective effect. Among other effects, they lower systemic blood pressure and renal plasma flow and effectively reduce urinary protein excretion. Renal delivery of ACE-inhibitors may increase this efficacy and reduce extra-renal side-effects. Renal targeting of an ACE-in-hibitor can also be useful in clarifying the contribution of local ACE inhibition to these reno-protective effects. 

The Russian literature indicates that rats exposed 4 hours/day to 1 mg/m for 11 months showed no outward indications of toxicity, but there was decreased diuresis, as well as some protein excretion in the urine. MCT penetrated the tails of rats and caused death. 

Keilani T, Danesh FR, Schlueter WA, Molteni A, Batile D. A sub-depressor low dose of ramipril lowers urinary protein excretion without increasing plasma potassium. Am J Kidney Dis 1999 33 450-7. 

Pharmacokinetics Rapidly absorbed following PO administration. Does not appear to bind to plasma protein. Excreted rapidly in urine, mostly unchanged. Half-life 2 hr. 

Pharmacokinetics Almost completely absorbed following PO administration. Absorption is reduced to 43% in congestive heart failure (CHF) patients. Not firmly bound to serum protein. Excreted in urine. Half-life 25 hr. 

Paroxetine is readily absorbed from the GIT with peak plasma concentration occurring within about five hours. It is widely distributed throughout body tissues and is about 95% bound to plasma proteins. Excretion is via the urine and the faeces, mainly as metabolites. 

While the initial goal of the discovery process is to express and purify the recombinant protein, without regard to cost and as quickly as possible, ultimately the production of a recombinant protein must be optimized to ensure that it can be produced at a reasonable cost. In most cases expression systems used to produce small quantities of recombinant protein for preliminary evaluation are not suitable to produce large quantities. Therefore, the gene inserted in the initial expression vectors must be systematically modified and recloned into vectors that can produce (1) a high yield of expressed protein, (2) stable host cell transfections, and (3) protein excretion. 

Disposition Aldesleukin is primarily eliminated by metabolism in the kidney. It is cleared from the circulation by both glomerular filtration and peritubular extraction with little or no bioactive protein excreted in the urine. 

Sotalol is well absorbed orally with bioavailability of approximately 100%. It is not metabolized in the liver and is not bound to plasma proteins. Excretion is predominantly by the kidneys in the unchanged form with a half-life of approximately 12 hours. Because of its relatively simple pharmacokinetics, solatol exhibits few direct drug interactions. Its most significant cardiac adverse effect is an extension of its pharmacologic action a dose-related incidence of torsade de pointes that approaches 6% at the highest recommended daily dose. Patients with overt heart failure may experience further depression of left ventricular function during treatment with sotalol. 

Prednisolone can cause an abrupt rise in proteinuria in patients with nephrotic syndrome. A placebo-controlled study in 26 patients aged 18-68 years with nephrotic syndrome has clarified the mechanisms responsible for this (163). Systemic and renal hemodynamics and urinary protein excretion were measured after prednisolone (125 mg or 150 mg when body weight exceeded 75 kg) and after placebo. Prednisolone increased proteinuria by changing the size-selective barrier of the glomerular capillaries. Neither the renin-angiotensin axis nor prostaglandins were involved in these effects of prednisolone on proteinuria. 

Fig. 5. A cell line selected for phosphate starvation resistance was con-stitutively induced for the excretion of APase into the medium. Three-day-old tomato cells selected for phosphate starvation resistance (PSR) and unselected cells (L. esculentum cv. VF36) were grown under Pi-sufficient conditions. Proteins excreted by the cells were separated by SDS-PAGE and immunoblotted with AP3 antiserum from which the Xylose-binding component had been removed via stem bromalin treatment (Goldstein, 1991). The selected cells showed constitutive excretion of high levels of APase protein based on the large signal obtained from the immunoblot. Measurement of enzyme activity gave a similar result (not shown).

Fig. 6. Under severe starvation conditions the epsi-APase and several other excreted proteins were present in the medium at very high levels relative to unstressed controls. Proteins excreted by cells growing 8 days -Pi or +Pi were separated via SDS-PAGE and immunoblotted using AP3 (A) or silver stained to show total protein (B). The psi enhancement of the epsi-APase (53.6 kDa) was clearly shown. The apparent molecular masses of several proteins selected for further study are indicated. Significant psi enhancement was shown for several of these proteins (Goldstein et al., 1989b).

D3. Dantal, J., Bigot, E., Bogers, W., Testa, A., Kriaa, F., Jacques, Y., Hurault de Ligny, B., Niaudet, P., Charpentier, B., and Soulillou, J. P., Effect of plasma protein adsorption on protein excretion in kidney-transplant recipients with recurrent nephrotic syndrome. N. Engl. J. Med. 330, 7-14 (1994). 

Unless M protein concentrations exceed 60 g/L, patients with multiple myeloma do not develop hyperviscosity syndrome. Despite the presence of plasma cells in bone marrow exceeding 10% and the presence of M protein exceeding 25 g/L, nearly 15% of patients with multiple myeloma are asymptomatic. However, asymptomatic patients presenting with IgA myeloma protein and M protein concentrations exceeding 30 g/L and Bence Jones-protein excretion in excess of 50 mg/day in presence of a lytic bone lesion can progress to multiple myeloma earlier than other, asymptomatic patients (Wl). 

Cell adhesion on a nonfunctional scaffold is mediated dominantly by nonspecific, entropically favored adsorption of a layer of cell adhesion proteins, excreted by the cell itself [61]. In order to obtain and retain the native function of these proteins, attempts are being made to tune the hydrophilicity or hydrophobicity of the scaffold surfaces [62], Different methods of surface activation are commonly applied, e.g., blending, copolymerization, plasma treatment, etching, radiation, chemical surface modification, coatings, and combinations of those. 

Salmonella in the gut lumen can induce a host inflammatory response mediated by several proteins excreted from the bacterial cytoplasm through Salmonella TTSS-1. These virulence factors may play a role in the influx of neutrophils into the intestine and the resulting inflammation that leads to diarrhea and other symptoms (Norris et al., 1998) (Fig. 5.1). Inflammation is an important component of innate immunity that plays a role in recruiting host immune cells to damaged tissue or invading microbes. Interaction with components of the innate immune system initiates a cascade of events that can lead to elimination of the microbe (Singh et al., 2009). 

---