Metabolic emergencies

Studies of canavanine interaction with the tobacco hornworm and J-. miTior also revealed the marked ability of canavanine.to inhibit whole organism incorporation of [ Hjthymidine and uridine into trichloroacetic acid-precipitated materials. When canavanine is provided simultaneously with the appropriate radio-labeled precursor, ample evidence for curtailed nucleic acid metabolism emerges but protein synthesis is unaffected (Table I, exp. I). In experiment II, canavanine is allowed to assimilate... 

Acute tumor lysis syndrome is a life-threatening metabolic emergency that results from rapid massive necrosis of tumor cells. There have been repeated reports of an acute tumor lysis syndrome when glucocorticoids are administered in patients with pre-existing lymphoid tumors (129). 

Several aspects of Schwann cell metabolism emerge as potential points of vulnerability to toxicants. The Schwann cell perikaryon (cell body) supports an enormous peripheral structure, the myelin sheath, which, if unwrapped, would dwarf the body of the Schwann cell (see Figure 30.4). Thus, as in the case of axonal transport in neurons, there may be specialized processes involved in supporting the topologically distant myelin. Furthermore, myelin has a specialized lipid and protein composition and a relatively rigid and ordered structure as compared to other membranes. Metabolic perturbations that potentially cause alterations in the composition of lipids and proteins assembled to form this membrane may cause destabilization and collapse of the myelin membrane. In this context, myelin might be much more vulnerable than plasma membranes of other cells. 

Since the SUMO pathway affects multiple pathways ranging from transcription, DNA repair, and intracellular trafficking over cell signaling and cell cycle control to basic metabolism, it is not suiprising that links to diseases and viral assaults are emerging. However, the field is not yet at a stage sufficiently developed for pharmacological intervention. Below we will describe selected examples for links of the SUMO pathway to diseases and viral functions. 

The dramatic decrease in the morbidity and mortality of HIV-infected individnals in the last decade, due to the wide use of HAART, has been somewhat tempered by the emergence of mid-long term toxicities. A characteristic body fat redistribntion and metabolic changes, inclnding dyslipidemia and insnlin resistance, are amongst the most prevalent and worrisome consequences (Carr et al. 2003). As HIV-infected individnals have increasing life expectancies, the risk for cardiovascnlar complications has emerged as an important canse of morbidity and mortality and preventive measnres should be considered to minimize their impact (Weber et al. 2006). 

As stated in section 5.1.1, some bacteria derive energy from food sources without the use of oxygen, whereas others are able to use this gas. The pathway of oxygen utilization itself is also a stepwise series of reactions and thus the overall picture emerges of cellular metabolism characterized by multistep reactions. 

The metabolic potential of yeasts has attracted attention in different contexts, and it has emerged that in contrast to many fnngi, they are able to bring about fission of aromatic rings. Some examples that illnstrate the varions possibilities are given below ... 

A contrasting pathway was found for the metabolism of 2-fluoro-4-nitrobenzoate by Nocardia erythropolis that does not involve loss of fluorine concomitant with decarboxylation (Cain et al. 1968). The pathway (Figure 9.30) therefore differs from what has subsequently emerged as the principal pathway for metabolism of nonhydroxylated 2-halogenated benzoates. 

Sulfonylurea herbicides are generally applied to crops as an early post-emergent herbicide. Crops that are tolerant to these herbicides quickly metabolize them to innocuous compounds. At maturity, residues of the parent compound in food and feed commodities are nondetectable. Metabolites are not considered to be of concern, and their levels are usually nondetectable also. For this reason, the residue definition only includes the parent compound. Tolerances [or maximum residue limits (MRLs)] are based on the LOQ of the method submitted for enforcement purposes and usually range from 0.01 to 0.05 mg kg (ppm) for food items and up to O.lmgkg" for feed items. There is no practical need for residue methods for animal tissues or animal-derived products such as milk, meat, and eggs. Sulfonylurea herbicides are not found in animal feed items, as mentioned above. Furthermore, sulfonylurea herbicides intentionally dosed to rats and goats are mostly excreted in the urine and feces, and the traces that are absorbed are rapidly metabolized to nontoxic compounds. For this reason, no descriptions of methods for animal-derived matrices are given here. 

Sulfentrazone is a broad-spectrum, pre-emergent herbicide that provides good control over broadleaf weeds, grasses and sedges in crops and turf. The metabolism of sulfentrazone in animals and plants is similar. The major plant metabolite of sulfentrazone is 3-hydroxymethyl sulfentrazone (HMS). The soybean tolerance of 0.05 mg kg includes residues of sulfentrazone plus its major metabolite, HMS. The rotational crop tolerance includes residues of sulfentrazone and its major metabolites, HMS and... 

It is critical to differentiate acute and chronic respiratory acidosis, as the acute form is often a medical emergency that requires intubation and mechanical ventilation, whereas the chronic form is typically a stable condition. The blood gases in Case Study 2 came from a patient with advanced emphysema who is a "C02 retainer" due to ineffective ventilation. Because this patient s disease is chronic, the elevated PaC02 developed very slowly and allowed for metabolic compensation. 

Disulfiram works by irreversibly blocking the enzyme aldehyde dehydrogenase, a step in the metabolism of alcohol, resulting in increased blood levels of the toxic metabolite acetaldehyde. As levels of acetaldehyde increase, the patient experiences decreased blood pressure, increased heart rate, chest pain, palpitations, dizziness, flushing, sweating, weakness, nausea and vomiting, headache, shortness of breath, blurred vision, and syncope. These effects are commonly referred to as the disulfiram-ethanol reaction. Their severity increases with the amount of alcohol that is consumed, and they may warrant emergency treatment. Disulfiram is contraindicated in patients who have cardiovascular or cerebrovascular disease, because the hypotensive effects of the disulfiram-alcohol reaction could be fatal in such patients or in combination with antihypertensive medications. Disulfiram is relatively contraindicated in patients with diabetes, hypothyroidism, epilepsy, liver disease, and kidney disease as well as impulsively suicidal patients. 

A 70-year-old man presents to the emergency department because of diffuse abdominal pain and nonbloody diarrhea. One day earlier he had been discharged from the hospital, where he had received ceftriaxone and levofloxacin for 7 days for an upper respiratory infection. Soon after going home, he passed numerous liquid brown stools. A few hours later, the patient became disoriented, and an ambulance was called. His medical history is unremarkable. Laboratory values White blood cell count 50,000 cells/mm3, hematocrit 43%, sodium 125 mmol/L, potassium 5.6 mmol/L, C02 14 mmol/L, and metabolic acidosis. An abdominal radiograph series show no evidence of obstruction. The patient was admitted to the hospital. 

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