Skin and Muscle

The natural polymers known as proteins make up about 15% by mass of our bodies. They serve many functions. Fibrous proteins are the main components of hair, muscle, and skin. Other proteins found in body fluids transport oxygen, fats, and other substances needed for metabolism. Still others, such as insulin and vasopressin, are hormones. Enzymes, which catalyze reactions in the body, are chiefly protein. 

Treated rats had 1000 mg/kg FW liver (vs. 4.7 in controls) lowered hemoglobin, hematocrit, and red cell counts mean survival time of 67 days hepatic and renal histopathology Dose-time-dependent increase in copper concentrations in liver, spleen, and lung little accumulation in muscle and skin. Reduced growth at 2.5 and 3.75 mg/kg BW daily reduced survival at 3.75 mg/kg BW. Maximum copper concentrations recorded, in mg/kg FW (vs. saline controls,) were 710 in liver (<5), 212 in kidney (<10), 7 in lung (<1.5), 27 in spleen (<2.0) 6 in bone (<2.0) and 2.2 in testes (<1.6) Increased serum ceruloplasmin and white blood cell number... 

Cardiac index and blood pressure must be sufficient to ensure adequate organ perfusion, as assessed by alert mental status, creatinine clearance sufficient to prevent metabolic azotemic complications, hepatic function adequate to maintain synthetic and excretory functions, a stable heart rate and rhythm, absence of ongoing myocardial ischemia or infarction, skeletal muscle and skin blood flow sufficient to prevent ischemic injury, and normal arterial pH (7.34 to 7.47) with a normal serum lactate concentration. These goals are most often achieved with a cardiac index greater than 2.2 L/min/m2, a mean arterial blood pressure greater than 60 mm Hg, and PAOP of 25 mm Hg or greater. 

Adult tissue-specific stem cells are present in other self-renewable organs, including the liver, pancreas, skeletal muscle, and skin. The heart, which until very recently was considered a terminally differentiated, postmitotic organ with a finite store of myocytes established at birth, may now be added to this list. It has recently been observed that hematopoietic stem cells (HSCs) can transdifferentiate into car-diomyocytes [33, 34] and that stem cells reside in the heart [35]. These resident cardiac stem cells (CSCs)... 

The rate at which an equilibrium concentration of a drug is reached in the extracellular fluid of a particular tissue will depend on the tissue s perfusion rate the greater the blood flow the more rapid the distribution of the drug from the plasma into the interstitial fluid. Thus, a drug will appear in the interstitial fluid of liver, kidney, and brain more rapidly than it will in muscle and skin (Table 3.2). The pharmacokinetic concept of volume of distribution (a derived parameter that relates the amount of drug in the body to the plasma concentration) is discussed more fully in Chapter 5. 

Hydralazine produces widespread but apparently not uniform vasodilation that is, vascular resistance is decreased more in cerebral, coronary, renal, and splanchnic beds than in skeletal muscle and skin. Renal blood flow and ultimately glomerular filtration rate may be slightly increased after acute treatment with hydralazine. However, after several days of therapy, the renal blood flow is usually no different from that before drug use. 

Amino Acids and Proteins. Proteins are the molecules that perform the functions of life. They can be enzymes that catalyze biological reactions, or they can be the receptor site on a membrane that binds a specific substance. Proteins are important parts of both bones—the so-called hard biologies—and the soft biologies such as muscle and skin. Any discussion of the structure of living organisms must begin with the structure of proteins. 

Isoprenaline stimulates pi and 32 adrenoceptors (pi>32) resulting in increased myocardial contractility and reduced peripheral vascular resistance. It does not act on a adrenoceptors. Cardiac output increases partly due to reduced afterload and an increase in heart rate. There is a diversion of blood to non-essential tissues, e.g. skeletal muscle and skin. Because of the decrease in peripheral vascular resistance arterial blood pressure and coronary perfusion pressure may decrease, which may predispose to myocardial ischaemia. 

Residue depletion studies with piglets orally dosed with 30 mg spectinomycin/kg bw/day for 5 consecutive days showed that the average concentrations of the parent drug in liver, kidney, muscle, and skin/fat were 1030, 7700, less than 300, and less than 394 ppb, respectively, at 3 days, and less than 198, 500, 300, and 26 ppb, respectively, at 14 days postdosing. Broilers given water dosed at 50 mg spectinomycin/kg bw/day for 5 consecutive days were not found to contain detectable spectinomycin concentrations (limit of detection 500 ppb for liver and kidney and 250 ppb for muscle and skin/fat) in any edible tissue even only 1 day after the last dose. 

Residue depletion studies in swine given an infeed medication of 75 mg thiophanate/kg bw/day showed mean thiophanate concentrations in liver, kidney, muscle, and skin/fat of 5550, 6600, 2600, and 16,200 ppb, respectively, at 1 day after dosing, and 180, 100, less than 100, and 250 ppb, respectively, at 3 days after dosing. However, residue concentrations were below 100 ppb in all tissues at 7 day withdrawal. 

Proteins are useful for their energy content, just as starches, sugars, and fats are, but perhaps the greatest importance of proteins lies with how our bodies use them for building such structures as enzymes, bones, muscles, and skin. 

Sweat loss of up to 21/h is common, rising to 3 l/li in hot and humid conditions. Loss of significant amounts of water reduces plasma volume. This impairs the delivery of blood to muscles and skin, eventually leading to loss of temperature control and heat exhaustion. When dehydration reaches 2% of body weight performance is impaired at 5% work capacity falls by about 30% (Saltin and Costill, 1988). Water is also lost in respiration but this is of less significance than sweating during strenuous activity. 

Large-scale deletions, insertions, and tandem duplications of mtDNA are usually not found in blood cells, and the proportions of mtDNA with point mutations in blood cells are generally lower than those in muscle of patients with mitochondrial disease (PI, W5). Thus, the absence of mtDNA mutation in blood samples cannot be used to exclude mitochondrial disease (L7, PI). On the other hand, higher levels of mutant mtDNA are usually found in postmitotic tissues such as cardiac and skeletal muscles and skin tissue of patients. Large-scale deletions or point mutations of mtDNA are generally detectable in muscle biopsies of about 70% of patients with mitochondrial disease (L7, PI). Some of these patients are affected by mutations in nuclear DNA. Other, unknown mutations in mtDNA or nuclear DNA are present in the rest of the patients. 

O Farrell, S., Dietary polyunsaturated fatty acids and oxidation damage to heart, skeletal muscle and skin, PhD Thesis, University of Liverpool, 1994. 

Clozapine-induced myokymia (weakness and reduced muscle tone, with undulating movements of the muscle and skin, accompanied by involuntary repetitive firing of grouped motor unit action potentials) has been reported (196). 

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