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By N. Jensgar. Alvernia College.

Take the point in which 50% of the active site of the enzyme will be saturated by substrate buy viagra super active 100 mg with visa erectile dysfunction drugs and glaucoma, Assume that at ½ Vmax-50% of the active site of enzyme becomes saturated discount viagra super active 50mg on line erectile dysfunction without drugs. Therefore: 11 Vo = ½ Vmax, at 50% saturation ½ Vmax = Vmax[S] Km + [S] 2[S] = Km + [S] Km= [S] Figure: Relationship between [S] and Km Characteristics of Km Km- can defined as the concentration of the substrate at which a given enzyme yields one-half its max. Small Km - A numerically small (Low) km reflects a high affinity of the enzyme for substrate because a low conc of substrate is needed to half saturate the enzyme- that is reach a velocity of ½ Vmax. High Km - A numerically large (high) Km reflects a low affinity of enzyme for substrate b/c a high conc of substrate is needed to half saturate the enzyme. Relationship of Velocity to Enzyme Concentration The rate of the reaction is directly proportional to enzyme concentration at all substrate concentration. For example, if the enzyme concentration halved, the initial rate of the reaction (Vo) is reduced to one half that of the original. Effect of Enzyme concentration on enzymatic reaction Order of Reaction When [S] is much less than Km, the velocity of the reaction is roughly proportional to the substrate concentration. The rate of reaction is then independent of substrate concentration and said to be zero order with respect to substrate concentration. Enzyme Inhibition Any substance that can diminish the velocity of an enzyme-catalyzed reaction is called an inhibitor and the process is known as inhibition. Example: Inhibition of triose phosphate dehydrogenate by iodo acetate which block the activity of the enzyme. In competitive inhibition the inhibitor and substrate compete for the same active site on the enzyme as a result of similarity in structure. A classical example is Malonate that competes with succinate and inhibits the action of succinate dehydrogenase to produce fumarate in the Krebs cycle. The enzyme can be also inhibited by oxalate and glutarate because of the similarity of this substance with succinate Eg. This competition blocks the conversion of these precursors, and of hypoxanthine and xanthine, to uric acid and result in lower serum urate levels. A Lineweaver-Burk Plot An alternative linear transformation of the Michaelis-Menten equation is the Eadie-Hofstee transformation: v/[S] = -v [1/Km] + [Vmax/Km] and when v/[S] is plotted on the y-axis versus v on the x-axis, the result is a linear plot with a slope of -1/Km and the value Vmax/Km as the intercept on the y- axis and Vmax as the intercept on the x-axis. Both the Lineweaver-Burk and Eadie-Hofstee transformation of the Michaelis-Menton equation are useful in the analysis of enzyme inhibition. Since most clinical drug therapy is based on inhibiting the activity of enzymes, analysis of enzyme reactions using the tools described above has been fundamental to the modern design of pharmaceuticals 15 Effect of Competitive inhibitors 1. This means that in the presence of a competitive inhibitor more substrate is needed to achieve ½ Vmax. Figure: Competitive inhibition Non-Competitive Inhibition In non-competitive inhibition the inhibitor binds at different site rather than the substrate-binding site. When the inhibitor binds at this site there will be a change in conformation of the enzyme molecules, which leads to the reversible inactivation of the catalytic site. Figure: Uncompetitive inhibition 17 Regulation of enzyme activity There are several means by which the activity of a particular enzyme is specifically regulated. Irreversible covalent Activation / Zymogen activation Some enzymes are secreted in an inactive form called Proenzymes or zymogens. Reversible Covalent Modification By addition of or removal of phosphate or adenylate, certain enzymes are reversibly activated and inactivated as per the requirement. Allosteric Modulation In addition to simple enzymes that interact only with substrates and inhibitors, there is a class of enzymes that bind small, physiologically important molecules and modulate activity in ways other than those described above. These are known as allosteric enzymes; the small regulatory molecules to which they bind are known as effectors. Allosteric effectors bring about catalytic modification by binding to the enzyme at distinct allosteric sites, well removed from the catalytic site, and causing conformational changes that are transmitted through the bulk of the protein to the catalytically active site(s). Feedback inhibition In allosteric regulation in which end products inhibit the activity of the enzyme is called” feedback inhibition”. Feedback regulation generally occurs at the earliest functionally irreversible step unique in the biosynthetic pathway. Enzymes those have function in plasma) For example: - the liver secretes zymogens of the enzymes involved in blood coagulation. In healthy individuals the levels of these enzymes are fairly constant and represent steady state in which the rate of release from cells into the plasma is balanced by an equal rate or removal from the plasma. Many diseases that cause tissue damage result in an increased release of intracellular enzymes into the plasma. The activities of many of these enzymes are routinely 19 determined for diagnostic purposes in diseases of the heart, liver, skeletal muscle, and other tissues.

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If it is not focused clearly purchase 50mg viagra super active with amex impotence research, rotate lenses into the aperture with your index finger until the optic disc is clearly visible as possible discount viagra super active 25mg on line erectile dysfunction test yourself. The hyperopic, or far- sighted, eye requires more‘’ plus’’(black numbers)sphere for clear focus; the myopic, or near-sighted, eye requires ‘’ minus’’(red numbers) sphere for clear focus. Now examine the disc for clarity of outline, color, elevating and condition of the vessels. To locate the macula, focus on the disc, then move the light approximately 2 disc diameters temporally. You may also have the patient look at the light of the ophthalmoscope, which will automatically place the macula in full view. The red-free filter facilitates viewing of the center of the macula, or the fovea. To examine the left eye, repeat the procedure outlined above except that you hold the ophthalmoscope in the left hand, stand at the patient’s left side and use your left eye. If the patient has a refractive error, try dialing up plus or minus lenses in the ophthalmoscope to bring the fundus into focus. It is difficult to see the fundus clearly so use a strong minus lens in the ophthalmoscope. Seat the baby on his mother’s lap, so that her hands restrain his arms and steady his head 2. Wrap the baby in a sheet or blanket, with his head on the examiners lap, and continue what you are going to do 3. In very difficult cases, it may be necessary to apply a drop of local anesthetic, and use a speculum to hold open the eyelids. Intra ocular pressure ƒ Should be measured in any patient with suspected glaucoma. Ahmed 5- Albert and Jakoboiec Principle and practice of ophthalmology 6- Up to date - (C) 2001 - www. At the end of the course the students are expected to have adequate knowledge about eyelid and lacrimal apparatus disease; the diagnosis and management of such diseases. Internal Hordeolum • a small abscess collection in the Meibomian glands • Caused by staphylococcus Symptoms pain, redness, swelling within eye lid Signs tender, inflamed mass within the eye lid. Treatment _ Hot compress _ Topical antibiotics _ If the above treatment fails, referral for. External Hordeolum /stye/ ¾ An acute staphylococcal infection of a lash follicle and its associated gland of zeis or moll. Chalazion - A chronic lipogranulomatous inflammatory lesion caused by blockage of meibomian gland orifices and stagnation of sebaceous secretion - Patient with acne roscea or seborrheic dermatitis are at increased risk of Chalazion formation which may be multiple or recurrent. Symptom ¾ Painless nodule within the eye lid Sign ƒ Non tender, firm, roundish mass within the eye lid. Molluscum contagiosum - Uncommon skin infection caused by a poxvirus - It is common in children and immunocompromized patient. Sign ¾ Single or multiple ¾ Pale, waxy ¾ Umblicated nodules ¾ If the nodule is located on the lid margin it may give rise to ipsilateral chronic follicular conjunctivitis and occasionally a superficial keratitis Treatment ¾ Expression ¾ Shaving and excision ¾ Destruction of the lesion by cauterization, cryotherapy E. Blepharitis ¾ a general term for inflammation of the eyelid ¾ Can be associated with conjunctivitis There are two main types of blepharitis 1. Entropion - Means the eyelids turn in wards then the eyelashes rub and damage the globe Treatment - Referral for surgical correction C. It can cause ambylopia if it is unilateral Treatment - Referral for surgical correction 31 3. Treatment - Hot compression - Systemic antibiotic -Incision and abscess drainage may be required Complication - Preseptal cellulitis - Orbital cellulitis Chronic dacryocystitis Symptoms - Tearing - Swelling over the medial aspect of the eye - Mucoid or purulent discharge with pressure on the lacrimal sac area. Preseptal cellulitis Definition: it is infection of the tissues anterior to the orbital septum Symptom - No visual reduction - Mild periorbital pain - Localized eyelid redness and swelling Sign - V/A is normal - Tender and hot eyelid - Ocular motility is normal Treatment - Ciprofloxacillin 500mg po bid for seven days. Orbital cellulitis An infection of orbital tissue posterior to the orbital septum. Symptom -Pain -Proptosis -Fever - Limited ocular movement -Visual reduction 33 Sign - V/A is reduced -Tender eye - Reduced to absent ocular motility Treatment It is an ophthalmic emergency that needs admission; intravenous antibiotics and close follow up. Ahmed 4 - Albert and Jacoboiec Principle And Practice Of Ophthalmology 5 - Up to date - (C) 2001 - www.

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Even the types of food and supplies you can buy on your trip may not be the same as those you get at home cheap 100 mg viagra super active fast delivery erectile dysfunction treatment old age. Before you travel generic viagra super active 25mg without prescription erectile dysfunction drugs used, work with your health care provider to plan your timing for medicine, food, and activity. Plan ahead for trips: ■ Keep snacks with you that could be used to prevent—or treat—low blood glucose. Keep medicines in the original pharmacy container with the printed label that clearly identifes the medicine. If you’re traveling in a different time zone, you may need to change your timing of food, medicine, and activity. It’s also a good idea to get your doctor to write a prescription for you to get insulin or supplies if needed. Your diabetes educator or other health care provider may be able to help you think of ways to deal with these problems. In support groups, people who have just found out they have diabetes can learn from people who have lived with it for a long time. They can also talk about how they take care of their health, how they prepare food, and how they get physical activity. Ask your health care team about support groups for people with diabetes and their families and friends. If there is not a support group in your area, you may want to call a diabetes organization (see the list on pages 127–129) It can help to talk with other people who about start- have problems like your own. Research shows that keeping your blood glucose level closer to normal can prevent or delay the onset of diabetic eye disease. Signs of Diabetic Eye Disease Since diabetic eye disease may be developing even when your sight is good, regular dilated eye exams are important for fnding problems early. If your blood pressure is higher than 130/80, ask your health care provider how to keep your blood pressure at a healthy level. Ask your health care provider to help you fnd an eye doctor who cares for people Get a complete eye exam each year. If you haven’t already had a complete eye exam, you should have one now if any of these conditions apply to you: ■ You’ve had type 1 diabetes for 5 or more years. Discuss Your Physical Activity Plan If you have diabetic eye disease, talk with your health care provider about the kind Think of a way to remind of physical activity that is yourself to get an eye best for you. An operation called a vitrectomy may help those who have lost their sight from bleeding in the back of the eye. If your sight is poor, an eye doctor who is an expert in low vision may be able to give you glasses or other devices that can help you use your limited vision more fully. You may want to ask your health care provider about support groups and job training for people with poor vision. A recent study shows that controlling your blood glucose can prevent or delay the onset of kidney disease. When the kidneys fail, a person has to have his or her blood fltered through a machine (a treatment called dialysis) several times a week or has to get a kidney transplant. If the tests show microalbumin in the urine or if your Work with your health care kidney function isn’t provider to prevent or treat normal, you’ll need to kidney problems. Protecting Your Kidneys Keep Your Blood Glucose Under Control High blood glucose can damage your kidneys as time goes by. Know the Effects of Some Medicines and X-Ray Dyes If you have kidney disease, ask your health care provider about the possible effects that some medicines and X-ray dyes can have on your kidneys. You’re more likely to have heart and blood vessel problems if you smoke cigarettes, have high blood pressure, or have too much cholesterol or other fats in your blood. Talk with your health care team about what you can do to lower your risk for heart and blood vessel problems. Signs of Heart and Blood Vessel Problems If you feel dizzy, have sudden loss of sight, slur your speech, or feel numb or weak in one arm or leg, you may be having serious heart and blood vessel  problems.

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World Health Organization discount viagra super active 25 mg overnight delivery zma impotence, Guidelines for the surveillance of drug resistance in tuberculosis discount 25mg viagra super active erectile dysfunction drugs cost. Use of thiacetazone, thiophen-2-carboxylic acid hydrazide, and triphenyltetrazolium chloride. Chou, Modeling the emergence of the “hot zones’” tuberculosis and the amplification dynamics of drug resistance. Yip, Surveillance of Mycobacterium tuberculosis drug resistance in Hong Kong, 1986–1999, after the implementation of directly observed treatment. Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. If you wish to reuse material from this work that is attributed to a third party, such as tables, fgures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third-party-owned component in the work rests solely with the user. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. However, the published material is being distributed without warranty of any kind, either expressed or implied. Hazim Antonette Remonte, Andrew Siroka, Karin Stenberg, Mukund Timimi led and organized all aspects of data management. Daniela Cirillo, Jonathan Daniels, Claudia Denkinger, Barbara Many people contributed to the analyses, preparation of Laughon, Diana Rozendaal, Mel Spigelman and Jennifer fgures and tables, and writing required for the main chapters Woolley for their reviews of Chapter 8. Production of the report was also supported by monitoring and evaluation unit for impeccable administrative the governments of Japan and the Republic of Korea. We also thank Sue Hobbs for we thank in particular Edith Alarcon, Mohamed Abdul Aziz, her outstanding work on the design and layout of this report. Samiha Baghdadi, Masoud Dara, Mirtha Del Granado, Her contribution, as always, was very highly appreciated. As in previous years, South Africa holds have been completed in seven countries: Ghana, Kenya, accounted for the largest share of the total (41%), followed Myanmar, the Philippines, Republic of Moldova, Timor Leste by Mozambique, Zimbabwe and Malawi. This year, a second page has been introduced to been provided from domestic sources, and this remains the each profle. Ensure inclusive and equitable quality education and promote lifelong learning opportunities for all Goal 5. Promote sustained, inclusive and sustainable economic growth, full and productive employment and decent work for all Goal 9. Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation Goal 10. Conserve and sustainably use the oceans, seas and marine resources for sustainable development Goal 15. Protect, restore and promote sustainable use of terrestrial ecosystems, sustainably manage forests, combat desertifcation, and halt and reverse land degradation and halt biodiversity loss Goal 16. Promote peaceful and inclusive societies for sustainable development, provide access to justice for all and build efective, accountable and inclusive institutions at all levels Goal 17. Strengthen the means of implementation and revitalize the Global Partnership for Sustainable Development a Acknowledging that the United Nations Framework Convention on Climate Change is the primary international, intergovernmental forum for negotiating the global response to climate change. Depending on the subheading of “Data, monitoring and accountability”, the indicator, examples include disaggregation by age, which specifcally refer to disaggregated data and mechanisms sex, location and economic status (e. Some indicators also given to the importance of death registration within national give particular attention to specifc subpopulations, such as vital registration systems for accurate tracking of causes of death (this is Part b of Indicator 17. Universal health coverage policy, and regulatory frameworks for case notifcation, vital registration, quality and rational use of medicines, and infection control D. Defnitions and reporting framework for The 10 components of the three pillars are shown in tuberculosis – 2013 revision (updated December 2014) Box 2.

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There is secondary nail thickening buy viagra super active 50 mg impotence questions, ridging generic 100 mg viagra super active fast delivery impotence exercise, discoloration, and occasional nail loss in chronic cases. Physical examination reveals a diffuse erythema and white patches that appear on the surfaces of the buccal mucosa, throat, tongue, and gums. The presence of retrosternal pain, epigastric pain, nausea, and vomiting may suggest esophageal candidiasis Vulvovaginal candidiasis: This is the second most common cause of vaginitis. A patch resembling thrush appears on the glans and may spread to the thighs, gluteal folds, buttocks, and scrotum. Treatment Candida intertrigo - Topical azoles and polyenes, including clotrimazole, miconazole, and nystatin, are effective. Paronychia - the most important intervention is drainage followed by oral antifungal therapy with either ketoconazole, fluconazole or itraconazole. Single daily dose of itraconazole taken for 3-6 months or a pulsed-dose regimen that requires a slightly higher dose daily for 7 days, followed by 3 weeks off therapy. Vulvovaginal candidiasis – Azole suppository or pessaries , in resistant case systemic therapy for 10 days. Warts Warts or verrucae are benign growths on the skin or mucous membranes that cause cosmetic problems as well as pain and discomfort. The incubation period of a wart is 2 to 9 months during which time an excessive proliferation of skin growth slowly develops. Common warts, especially in children, do not necessarily need to be treated, because they exhibit a high rate of spontaneous remission. Treatment ™ Salicylic acid 25% ointment twice daily followed by cutting or scraping ™ Preparation of salicylic acid 5-20% and lactic acid 5-20 in collodion are easier to use ™ Electrodessication and curettage ™ Freezing with liquid nitrogen if available. Protect the skin around the wart with Vaseline apply the podophyllin with a match stick carefully on the top of the war and wash after 6 hours. Molluscum contagiosum Molluscum contagiosum is a viral infection of the skin that causes discrete papules that may be mistaken for warts. The rash of molluscum contagiosum is characterized by discrete, 2 to 5 mm papules that are flesh- colored (skin color) and dome-shaped with a central umbilication (depressed centre). Cryosurgery - Using liquid nitrogen to freeze the lesion Salicylic Acid (Compound W) - A solution applied to the lesion with or without tape occlusion 3. Pathogenesis of herpes simplex virus 30 Primary infection Latency Transmission can occur in all stages; more at the primary Reactivation stage What causes latency? Herpetic Whithlow Infection of pulp of fingertips, it could appear after touching a primary lesion of ones owns lesion or that of others. Lesions are bilateral and symmetrical, inguinal lymph nodes may be enlarged, fever and flu like symptom may be there. Manifestations: Skin vesicles, Encephalitis, Hepatitis, Pneumonia, Coagulopathy Mortality rate (M/R) >50% in ideal setting. Scabies Definition: - scabies is one of the commonest intensely pruritic, highly contagious infectious conditions of the skin caused by a mite Sarcoptis scabei and transmitted by close personal and sexual contacts 34 Historically It has been recognized as a disease for over 2500 years. In 1687 Francesco Redi identified Sarcoptes scabei Scabies is one of the first diseases with a known cause. Romans used the term to describe any pruritic skin disease; so, it has been known as the great imitator Etiologic agent Sarcoptes scabei var. Epidemiology 9 Commoner in children and adolescents 9 It is a disease of disadvantaged community 9 Epidemic occurs during wars and social upheavals 9 Endemic in many developing countries Transmission Pathogenesis Female and male make mating on the surface of the skin. The male mite dies and the gravid female mite burrows into the epidermis lays up to 3 eggs per day for the duration of her 30-60 day lifetime. It starts on the wrist, finger webs and on the medial sides of fingers, the flexor aspect of 35 the wrist, the elbows and the anterior axillary folds, the genitalia and inner thighs and the gluteal folds More disseminated presentation in infants and toddlers. Scabies in infants and young children 9 Distribution and morphology:- generalized 9 The face the scalp, palms an soles are affected 9 Papules, vesicle and pustules 9 Secondary eczematization and impetiginazation are common Crusted (Norwegian) scabies In 1848, Danielssen and Boeck described a highly contagious variant of scabies occurring in immunocompromised patients, elderly or mentally incompetent patients. In Norwegian scabies, pruritus may not be there (in about 50% of the cases do not itch) It is psoriasiform and generalized with nail changes and scalp involvement Skin becomes thickened and involves all part of skin including face, palms and sales.

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