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V. Finley, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.
Professor, University of Arizona College of Medicine – Tucson
Spectrophotometric assays exploit the ability of a substrate or product to absorb light. In each case, the rate of change in optical density at 340 nm will be proportionate to the quantity of enzyme present. Many Enzymes Are Assayed by Coupling to a Dehydrogenase the assay of enzymes whose reactions are not accompanied by a change in absorbance or fluorescence is generally more difficult. In some instances, the product or remaining substrate can be transformed into a more readily detected compound. In other instances, the reaction product may have to be separated from unreacted substrate prior to measurement. An alternative strategy is to devise a synthetic substrate whose product absorbs light or fluoresces. For example, p-nitrophenyl phosphate is an artificial substrate for certain phosphatases and for chymotrypsin that does not absorb visible light. However, following hydrolysis, the resulting p-nitrophenylate anion absorbs light at 419 nm. Typically, a dehydrogenase whose substrate is the product of the enzyme of interest is added in catalytic excess. Enzymes Assist Diagnosis of Myocardial Infarction An enzyme useful for diagnostic enzymology should be relatively specific for the tissue or organ under study, should appear in the plasma or other fluid at a time useful for diagnosis (the "diagnostic window"), and should be amenable to automated assay. Enzymes that only appear in the plasma 12 h or more following injury are thus of limited utility. Tissue-specific expression of the H and M genes determines the relative proportions of each subunit in different tissues. Pattern A is serum from a patient with a myocardial infarct; B is normal serum; and C is serum from a patient with liver disease. Immunological measurement of plasma levels of cardiac troponins I and T provide sensitive and specific indicators of damage to heart muscle. The search for additional markers for heart disease, such as ischemia modified albumin, and the simultaneous assessment of a spectrum of diagnostic markers via proteomics, continues to be an active area of clinical research. Enzymes also can be employed in the clinical laboratory as tools for determining the concentration of critical metabolites. For example, glucose oxidase is frequently utilized to measure plasma glucose concentration. Enzymes are employed with increasing frequency as tools for the treatment of injury and disease. The isolation of an individual enzyme, particularly one present in low concentration, from among the thousands of proteins present in a cell can be extremely difficult. If the gene for the enzyme of interest has been cloned, it generally is possible to produce large quantities of its encoded protein in Escherichia coli or yeast. However, not all animal proteins can be expressed in active form in microbial cells, nor do microbes perform certain posttranslational processing tasks. For these reasons, a gene may be expressed in cultured animal cell systems employing the baculovirus expression vector to transform cultured insect cells. The gene of interest is linked to an oligonucleotide sequence that encodes a carboxyl or amino terminal extension to the encoded protein. The resulting modified protein, termed a fusion protein, contains a domain tailored to interact with a specific affinity support. One popular approach is to attach an oligonucleotide that encodes six consecutive histidine residues. The expressed "His tag" protein binds to chromatographic supports that contain an immobilized divalent metal ion such as Ni2+. Fusion proteins also often encode a cleavage site for a highly specific protease such as thrombin in the region that links the two portions of the protein. Specific proteases can then remove affinity "tags" and generate the native enzyme. Site-Directed Mutagenesis Provides Mechanistic Insights Once the ability to express a protein from its cloned gene has been established, it is possible to employ site-directed mutagenesis to change specific aminoacyl residues by altering their codons. Used in combination with kinetic analyses and x-ray crystallography, this approach facilitates identification of the specific roles of given aminoacyl residues in substrate binding and catalysis. For example, the inference that a particular aminoacyl residue functions as a general acid can be tested by replacing it with an aminoacyl residue incapable of donating a proton.
Schweintang (Bladderwrack). Tadalafilum.
- Are there safety concerns?
- Dosing considerations for Bladderwrack.
- What is Bladderwrack?
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- Are there any interactions with medications?
- Thyroid problems including an over-sized thyroid gland (goiter), iodine deficiency, obesity, arthritis, achy joints (rheumatism), hardening of the arteries (arteriosclerosis), digestive problems, "blood cleansing," constipation, and other conditions.
Source: http://www.rxlist.com/script/main/art.asp?articlekey=96710
The ureters run directly inferior to the uterine arteries before feeding into the bladder. It is the most common cancer in adult males and the second most common cause of death due to cancer in adult males. This condition is more common in African-American men and is usually asymptomatic until advanced. Prostate cancer can invade locally or spread via the lymphatics or bloodstream to bone, lung, and liver. This patient has a history of physical labor and may have sought medical care for back pain earlier in life. Given his current symptoms of weight loss, fatigue, and trouble urinating, he most likely has prostate cancer that has metastasized to bone, not simply a back problem. Lack of primary care can be a risk factor for prostate cancer, but in this patient it is not the most important risk factor. Smoking is a risk factor for prostate carcinoma, but it is not the most important risk factor. However, the arrest of blood vessel growth is not known to be inhibited directly by human papillomavirus. Mitogenic signal transduction is commonly increased by oncogenes, such as myc, src, or bcr-abl. Additionally, the lack of aldosterone leads to salt wasting, which can present with hypovolemia and hypotension. Instead, it can result in hypertension because the deficient enzyme allows an accumulation of an aldosterone precursor (11-deoxycorticosterone) that acts as a mineralocorticoid to cause salt retention and hypervolemia. This enzyme has a role in the conversion of progesterone and progenolone to precursors that will go on to form cortisol, testosterone, and estrogen. The intermediates that build up will produce an excessive amount of aldosterone, resulting in hypertension and hypokalemia. At puberty these patients may suddenly experience virilization of the external organs due to the increase in testosterone. Complete androgen insensitivity is a result of a mutation in the androgen receptor gene. They typically present as normal-appearing girls, with normal breast development and body habitus, who consult their physician when they do not begin menstruation. These patients typically have decreased or absent axillary and pubic hair and are taller than average. The increased risk in obese patients is from increased aromatization in peripheral tissues, resulting in higher levels of circulating estrogen. Endometrial tissue is estrogen sensitive, and higher levels of circulating estrogen lead to increased glandular proliferation and increased risk for dysplastic transformation. Because weight is one of the modifiable risk factors for endometrial cancer, lowering the body mass index in patients at risk for developing endometrial cancer is a good method of primary prevention. Alcoholism has little relation to endometrial cancer, but is strongly associated with chronic pancreatitis, pancreatic adenocarcinoma, and cirrhosis of the liver. Smoking is also a risk factor for these condi- tions, but tobacco use is actually protective against endometrial cancer to a certain extent. Early sexual activity has little relation to endometrial cancer but is a major risk factor for cervical cancer. Other risk factors for cervical cancer include multiple sex partners, human papillomavirus infection, coinfection with other sexually transmitted diseases, smoking, and low socioeconomic status. Multiparity protects against endometrial cancer, because it gives the endometrium a "resting period" in which it is not actively proliferating through the menstrual cycle. By the same logic, menopause occurring at or after 53 years of age would put the patient at increased risk because of an increased amount of endometrial active proliferation. Although progesterone has a protective effect, estrogenprogesterone synthetic birth control products have not shown any benefit in reducing the incidence of endometrial cancer.
Inability to recall important personal information, usually subsequent to severe trauma or stress. May be accompanied by dissociative fugue (abrupt travel or wandering during a period of dissociative amnesia, associated with traumatic circumstances). Dissociative amnesia Dissociative disorders Dissociative identity disorder Depersonalization/ derealization disorder Formerly known as multiple personality disorder. Delirium "Waxing and waning" level of consciousness with acute onset; rapid in attention span and level of arousal. Characterized by disorganized thinking, hallucinations (often visual), illusions, misperceptions, disturbance in sleepwake cycle, cognitive dysfunction. Most common presentation of altered mental status in inpatient setting, especially in the intensive care unit and with prolonged hospital stays. Characterized by memory deficits, apraxia, aphasia, agnosia, loss of abstract thought, behavioral/personality changes, impaired judgment. A patient with dementia can develop delirium (eg, patient with Alzheimer disease who develops pneumonia is at risk for delirium). Reversible causes: hypothyroidism, depression, vitamin deficiency (B1, B3, B12), normal pressure hydrocephalus, neurosyphilis. In elderly patients, depression and hypothyroidism may present like dementia (pseudodementia). Psychosis Delusions Distorted perception of reality characterized by delusions, hallucinations, and/or disorganized thought/speech. Types include erotomanic, grandiose, jealous, persecutory, somatic, mixed, and unspecified. Speech may be incoherent ("word salad"), tangential, or derailed ("loose associations"). Perceptions in the absence of external stimuli (eg, seeing a light that is not actually present). Types include: Visual-more commonly a feature of medical illness (eg, drug intoxication) than psychiatric illness. Auditory-more commonly a feature of psychiatric illness (eg, schizophrenia) than medical illness. Olfactory-often occur as an aura of temporal lobe epilepsy (eg, burning rubber) and in brain tumors. Tactile-common in alcohol withdrawal and stimulant use (eg, cocaine, amphetamines), delusional parasitosis, "cocaine crawlies. Negative symptoms (affective flattening, avolition, anhedonia, asociality, alogia) Brief psychotic disorder-lasting < 1 month, usually stress related. Schizoaffective disorder-Meets criteria for schizophrenia in addition to major mood disorder (major depressive or bipolar). To differentiate from a major mood disorder with psychotic features, patient must have > 2 weeks of hallucinations or delusions without major mood episode. Presents earlier in men (late teens to early 20s vs late 20s to early 30s in women). Negative symptoms often persist after treatment, despite resolution of positive symptoms. Functioning otherwise not impaired (eg, a woman who genuinely believes she is married to a celebrity when, in fact, she is not). Mood disorder Characterized by an abnormal range of moods or internal emotional states and loss of control over them. Severity of moods causes distress and impairment in social and occupational functioning. Includes major depressive disorder, bipolar disorder, dysthymic disorder, and cyclothymic disorder. Episodic superimposed psychotic features (delusions or hallucinations) may be present.
Diseases
- Hypomandibular faciocranial dysostosis
- Marchiafava Micheli disease
- Pancreatic lipomatosis duodenal stenosis
- Polyposis skin pigmentation alopecia fingernail changes
- Nystagmus
- Pycnodysostosis
- Chromosome 17 ring
- Cerebro oculo dento auriculo skeletal syndrome
- Orstavik Lindemann Solberg syndrome
- Hypoplastic left heart syndrome
Infants may initially become constipated and then develop generalized muscle weakness ("floppy baby"). The organism is spread through the ingestion of contaminated canned or bottled food. IgA protease is produced by some bacteria so they can cleave secretory IgA and colonize mucosal areas; Neisseria gonorrhoeae, Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae are the most well known. Exotoxin A is produced by Pseudomonas aeruginosa as well as some Streptococcus species. However, none of these organisms produce the symptoms seen in this case or is transmitted by honey ingestion. Lecithinase is produced by Clostridium perfringens and is responsible for the development of gas gangrene, cellulitis, and diarrhea. Lipopolysaccharide, also called endotoxin, is produced by gramnegative bacteria and Listeria. These organisms are found in soil in dry areas of the southwestern United States, Mexico, and Central and South America. About 60% of these infections cause no symptoms, and in the remaining 40% of cases, the symptoms can range from mild to severe. Severe forms of the infection can present with bloodtinged sputum, loss of appetite, weight loss, a painful red rash on the legs, and change in mental status. Treatment with amphotericin B or fluconazole is usually required only in severe, disseminated disease. In a patient with fever, chills, and flu-like symptoms who has recently returned from Namibia, there is concern for infection by Plasmodium species, which cause malaria. The time course and pattern of symptoms depend on the Plasmodium species with which the patient is infected. Treatment is tailored to the geographic area of infection and the Plasmodium species involved; agents include chloroquine, hydroxychloroquine, and atovaquone-proguanil. Sickness after travel to the Mississippi and Ohio River valleys is suggestive of histoplasmosis. Although histoplasmosis typically does not present symptomatically, some patients experience a flu-like illness with fever, cough, headaches, and myalgias. On microscopy, histoplasmosis appears as spherules filled with endospores, as opposed to the hyphae and spherules observed in the sputum of those with coccidiomycosis. A wound while gardening, such as a thorn prick, can cause inoculation with Sporothrix schenckii. This fungus can be found in various environments, including sphagnum moss, decaying vegetation, hay, and soil. When S schenckii is introduced into the skin, it causes a local pustule or ulcer with nodules along the draining lymphatics (ascending lymphangitis). If the mother becomes infected during pregnancy, the pathogens can cross the placenta and infect the fetus. The virus crosses the placenta in the first trimester and causes congenital abnormalities that range from deafness to cataracts to cardiovascular abnormalities. Because blood is shunted, there is a widening of pulse pressure (the difference between systolic and diastolic). Herpes simplex virus type 2 is also one of the most common causes of neonatal encephalitis. The class triad of symptoms that develop include chorioretinitis, hydrocephalus, and intracranial calcifications. This type of indolent lymphoma is believed to be associated with infection by the organism Helicobacter pylori. Eradication of the infection with antibiotics and proton-pump inhibitors is often sufficient to cause regression of the lymphoma.
