ENZYMES

INTRODUCTION: In our daily life we have things that aid in smooth running of the others let’s say; in a motor engine you put oil to lubricate the engine.  In sauce, we put cooking oil to make it delicious.  On tea, we put sugar to make it sweet.  In the human body systems the enzymes act like sugar in tea, oil in an engine or cooking oil in sauce.   Enzymes are biocatalysts and protein in nature.  Life is possible due to the co-ordination of numerous metabolic reactions inside the cells.  Proteins can be hydrolyzed with hydrochloric acid by boiling for a very long time; but inside the body, with the help of enzymes, proteolysis takes place within a short time at body temperature.  Enzyme catalysis is very rapid; usually 1 molecule of an enzyme can act upon about 1000 molecules of the substrate per minute.  Lack of enzymes will lead to block in metabolic pathways causing inborn errors of metabolism.  The substance, upon which an enzyme acts, is called the substrate.  The enzyme will convert the substrate into the product or products.

CHARACTERISTICS OF ENZYMES:  Almost all enzymes are proteins.  Enzymes follow the physical and chemical reactions of proteins.  They are heat labile.  They are water-soluble.  They can be precipitated by protein precipitating reagents including ammonium sulfate or trichloroacetic acid.  They contain 16% weight as nitrogen.

CLASSIFICATION OF ENZYMES:  When early workers isolated certain enzymes, whimsical names were given.  Some of these, such as Pepsin, Trypsin, Chymotrypsin, and many others are still used.  Later, it was agreed to call the enzymes by adding the suffix "-ase" to the substrate.  Thus in that respect, enzyme Lactase acts on the substrate lactose, and the products glucose and galactose are formed.  Enzymes that hydrolyse starch (amylose) are termed as amylases; those that dehydrogenate the substrates are called dehydrogenases.  These are known as the trivial names of the enzymes.  

OXIDOREDUCTASES:  Transfer of hydrogen or addition of oxygen; e.g. Lactate dehydrogenase (NAD); Glucose-6-phosphate dehydrogenase (NADP); Succinate dehydrogenase (FAD); di-oxygenases.  

TRANSFERASES: Transfer of groups other than hydrogen.  Example, Aminotransferase. (Subclass: Kinase, transfer of phosphoryl group from ATP; e.g. Hexokinase).  

HYDROLASES: Cleave bond and add water; e.g. Acetyl choline esterase; Trypsin.  

LYASES: Cleave without adding water, e.g. Aldolase; HMG CoA lyase; ATP Citrate lyase. (Subclass: Hydratase;add water to a double bond).  

ISOMERASES: Intramolecular transfers. They include racemases and epimerases. Example, Triose phosphate isomerase.  

LIGASES: ATP dependent condensation of two molecules, e.g. Acetyl CoA carboxylase; Glutamine synthetase; PRPP synthetase.

RELATED;

1.  INSULIN  

2.  GLUCAGON

3.  BIOCHEMISTRY
[REFERENCES]

ANTIMICROBIAL DRUG RESISTANCE

 

OBJECTIVES OF THIS ARTICLE:  By the end of this article, the reader will be able to;

1.  Understand the reason some microbes don't die from commonly used antibiotics.

2.  Identify the reasons microbes become resistant to drugs

3.  Predict the possible consequences of irrational drug used especially antibiotics.

INTRODUCTION:  The drugs that are used to treat microbes are termed antibiotics and they are of different classes, types and with varying duration of action and dosage regimens.  With the introduction of antimicrobial agents, it was thought that soon mankind would get rid of the infectious diseases.  But this was not to be.  One of the major factor contributing to the persistence of infectious diseases has been the tremendous capacity of the microorganisms for circumventing the action of inhibitory drugs.  This ability has also offered a serious threat to the future usefulness of present day chemotherapeutic agents.  The basis of drug resistant strains could be genetic or non-genetic.  [ANTIMICROBIAL AGENTS]

ORIGIN OF DRUG RESISTANT STRAINS:  The drug resistant strains arise either by mutation and selection or by genetic exchange in which a sensitive organism receives the genetic material or part of DNA, from the resistant organism and the part of DNA carries with it the information of mode of inducing resistance against one or multiple antimicrobial agents.  The drug resistance can arise by random mutation and when with it the organism becomes resistant to a drug, the application of that drug shall select out the resistant organisms and let them multiply.  [STRUCTURE OF DNA]

TRANSMISSIBLE (INFECTIOUS) DRUG RESISTANCE:  Apart from chromosomal resistance, extrachromosomal material which is called as plasmid (or episome) is also capable of conferring resistance to antibiotics.  There is adequate evidence to suggest that transfer of resistance can occur within the intestinal tract of human beings as well as the animals.

BIOCHEMICAL MECHANISMS OF DRUG RESISTANCE:  The biochemical changes which are seen in bacteria which have become resistant due to mutation are:  

(1)            Increased synthesis of drug antagonist Decreased permeability to drug  

(2)            Increased destruction of inhibitor  

(3)            Induction of different relative affinity of substrate and antagonist. The mechanism of drug resistance induced by plasmids is different than what is seen in mutated organism.

RELATED;

1.  BETA LACTAMASE INHIBITORS

2.  DYNAMICS OF DRUGS AND THE HUMAN BODY

3.  PHARMACOLOGY AND THERAPEUTICS

[REFERENCES]

DETERMINANTS OF PATHOGENICITY FOR CLOSTRIDIUM TETANI

Introduction:  Tetanus toxin is one of the most poisonous substances known and for technical reasons, there is no in vitro test to detect its activity.  Toxicity is observed by assaying the toxin in experimental animals.  There are two products liberated by C.tetani and one is a classical neurotoxin known as tetanospasmin while the other is a haemolysin known as tetanolysin.  The haemolysin is heat labile and inactivated by oxygen.  It is liberated by those strains which do not produce neurotoxin.

Kinetics of the toxin:  The toxin is relatively heat labile being destroyed at 65°C in 5 minutes however, it is stable in dry state.  It is not absorbed from the gastrointestinal tract and may be inactivated by gastric juice meaning that there are no receptors for it in the GIT lumen, and the chemical makeup of the toxin cannot withstand acidic pH.  Treatment of  this toxin with formaldehyde results in polymerization of toxin and results into formation of a product (toxoid) which is non-toxic but antigenic.  This is one basis for prevention of tetanus, where the polymer is formed between formaldehyde and tetanus toxoid.

Mode of action of the toxin:  The molecular basis for the action of tetanospasmin is not clearly known. The site of action is the nerve endings that are high in toxin fixing capacity.  The toxin specifically affects the synaptic junction of nerves by preventing the inhibition or erasing of nerve impulses once they have crossed the synaptic junctions.  In this case, the nerve continues to send impulses, a condition that results in spasmodic contraction (tetany) of the involved muscles.  

Symptoms of toxicity by clostridium tetani:  Early symptoms are muscle stiffness with the muscles of the jaw often developing spasms first.  This condition gives the disease its common name of lockjaw.   As the disease progresses, spasms develop in other muscles.  The spasms may be brief but can occur frequently and cause great pain and exhaustion.  Respiratory complications are many and death rate is high, especially in young children and elderly persons.

RELATED;

1.  CLOSTRIDIUM SPP

REFERENCES

 

HAEMOPHILUS INFLUENZAE

INTRODUCTION: Hemophilic bacteria are so designated because they require growth factors contained in blood. The most important human pathogen in this genus is H. influenzae. Other Haemophilus species either infect only animals or are found in the normal human mucosal flora. Normal flora

These latter include H. parainfluenzae, H. hemolyticus, H. segnis, H. aphrophilus, and H. paraphrophilus. These species can cause infections on occasion.

MORPHOLOGY AND CULTURE: Haemophilus are small compared to other bacteria, often encapsulated, non-motile, Gram-negative rods. H. influenzae is a facultative anaerobe requiring growth factors X and V in its culture medium. The X factor is hemin, required by the bacteria to synthesize enzymes containing heme including; cytochromes, catalase, and oxidases. The X factor requirement is greatly reduced in anaerobic culturing. The V factor was identified as NAD or NADP. A standard blood agar plate does not contain sufficient free V factor. Some bacteria, in particular Staphylococcus aureus, produce excess NAD and even secrete this coenzyme into the medium. That is why H. influenzae can proliferate in the immediate vicinity of S. aureus colonies. In medical microbiology, this is known as the satellite phenomenon. The medium normally used to culture H. influenzae is chocolate agar containing sufficient amounts of the X and V factors.

PATHOGENESIS AND CLINICAL PICTURES: H. influenzae is a mucosal parasite of the upper respiratory tract present in 30–50% of healthy persons. The strains usually found are nonencapsulated and therefore hardly virulent. The capsule protects the cells from phagocytosis and is thus the primary determinant of pathogenicity.  Pathogenicityof microbes

Others include the affinity of H. influenzae to respiratory tract mucosa and meninges and production of an IgA1 protease. H. influenzae infections are seen frequently in children aged from six months to four years of age due to the low levels of anticapsule antibodies in this age group. Maternal antibodies still protect children during the first months of life. The body has built up a sufficient store of antibodies by the age of four. Any list of potential clinical developments must begin with meningitis, followed by epiglottitis, pneumonia, empyema, septic arthritis, osteomyelitis, pericarditis, cellulitis, otitis media, and sinusitis.

Haemophilus infections in adults are usually secondary complications of severe primary illnesses or the result of compromised immune defenses. The most frequent complication is an acute exacerbation of chronic bronchitis. Pneumonias caused by H. influenzae are also observed, often as superinfections following viral influenza. In immunocompromised adults, even the nonencapsulated strains can cause infections of the upper and lower respiratory tract.

DIAGNOSIS: The method of choice is identification of the pathogen in cerebrospinal fluid, blood, pus, or purulent sputum using microscopy and culture assays. Satelliting on blood agar is an indication of a V factor requirement. An X factor requirement is confirmed most readily by the porphyrin test, with a negative result in the presence of H. influenzae.

THERAPY: In view of the increasing number of betalactamase-producing H. influenzae strains observed in recent years, penicillinase-stable betalactam antibiotics should be used to treat these infections. The likelihood that a strain produces betalactamase is 5–30% in most countries. 4-quinolones are an alternative to betalactams that should not, however, be used in children. The agent of choice in meningitis is ceftriaxone.

RELATED;

1.  STREPTOCOCCUS  

2.  TREPONEMA PALLIDUM

3.  MEDICAL MICROBIOLOGY

REFERENCES

DRUG DISTRIBUTION

Introduction: Distribution involves the transport of drugs throughout the body. The simplest factor determining distribution is the amount of blood flow to body tissues. The heart, liver, kidneys, and brain receive the most blood supply. Skin, bone, and adipose tissue receive a lower blood supply; therefore, it is more difficult to deliver high concentrations of drugs to these areas. The physical properties of the drug greatly influence how it moves throughout the body after administration. Drug administration techniques

Drug solubility in lipids:  Lipid solubility is an important characteristic, because it determines how quickly a drug is absorbed, mixes within the bloodstream, crosses membranes, and becomes localized in body tissues. Lipid-soluble agents are not limited by the barriers that normally stop water-soluble drugs; thus, they are more completely distributed to body tissues. Some tissues have the ability to accumulate and store drugs after absorption. The bone marrow, teeth, eyes, and adipose tissue have an especially high affinity, or attraction, for certain medications. Examples of agents that are attracted to adipose tissue are thiopental, diazepam, and lipid-soluble vitamins. 

Tetracycline binds to calcium salts and accumulates in the bones and teeth. Once stored in tissues, drugs may remain in the body for many months and are released very slowly back to the circulation. 

Extent of drug distribution:  Not all drug molecules in the plasma will reach their target cells, because many drugs bind reversibly to plasma proteins, particularly albumin, to form drug–protein complexes. Drug–protein complexes are too large to cross capillary membranes; thus, the drug is not available for distribution to body tissues. Drugs bound to proteins circulate in the plasma until they are released or displaced from the drug–protein complex. 

Only unbound (free) drugs can reach their target cells or be excreted by the kidneys. Some drugs, such as the anticoagulant warfarin, are highly bound; 99% of the drug in the plasma is bound in drug–protein complexes and is unavailable to reach target cells. Drugs and other chemicals compete with one another for plasma protein–binding sites, and some agents have a greater affinity for these binding sites than other agents. 

Effect of drugs and food:  Drug–drug and drug–food interactions may occur when one drug displaces another from plasma proteins. The displaced medication can immediately reach high levels in the bloodstream and produce adverse effects. Drugs such as aspirin or valproates, for example, displace Coumadin from the drug–protein complex, thus raising blood levels of free Coumadin and dramatically enhancing the risk of hemorrhage. Most drug guides give the percentage of medication bound to plasma proteins; when giving multiple drugs that are highly bound, the nurse should monitor the patient closely for adverse effects.

RELATED;

1.  SOLUBILITY OF MEDICAL COMPOUNDS

2.  DYNAMICS OF DRUGS AND THE HUMAN BODY

3.  PHARMACODYNAMICS

4.  DIAZEPAM

5.  PLASMA PROTEINS

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THE ORAL ROUTE OF DRUG ADMINISTARTION

THE ORAL ROUTE OF DRUG ADMINISTARTION:  The oral route is the most commonly used route of drug administration in both conscious patients and children.  This is when you take the drug via the mouth and swallow it with aid of clean drinking water.  The drug then will be taken to the stomach and then to the other parts of the Gastrointestinal Tract also sometimes known as alimentary canal.  It is mainly used in conscious patients and when eating and swallowing functions normally, or when the patient can listen to commands.  Drugs that are taken via this route goes all the way to the intestines via the stomach, and some get absorbed into the circulatory system while others may remain and work within the gastrointestinal tract like in case of deworming tablets.  For other drugs such as Mebendazole and Albendazole, the effects may be localised in the GIT and less or non of it may be absorbed into the systemic circulation.  This allows them to act up on the intended microbial infestations within the intestines and also helps in minimizing possible side effects.

REASONS FOR USING THE ORAL ROUTE:  There several reasons why drugs are given via this route and this article, let us look at one by one but before we continue, if you have not been following us, click here to read more about the routes of drug administration, and here to read about dynamics of drugs in the human body.

1.  The fast pass metabolism of drugs:  Among most of the drugs we take, there is always a requirement of the drug to pass through the liver first, and then back to the gastrointestinal tract for reabsorption.  This is known as the fast pass effect and the GIT is the best route for such metabolism.  In this case, it is the requirement for the liver to break down part of the drug or conjugate it.

2.  Moderation of bioavailability:  Not all the quantity of the drug is required to directly enter the circulation in most cases.  Sometimes some drugs may be very toxic and the oral route allows some of the drug to be absorbed slowly and takes sometime before it reaches the systemic circulation.

3.  Non invasive:  The oral route does not require sophisticated procedures on the human body and therefore the patient will not be exposed to introduction of microbial pathogens in blood.  This is not so, especially with other routes of drug administration where there is a requirement for use of injections.

DISADVANTAGES OF USING THE ORAL ROUTE:  Like any other medical procedure, the oral route has setbacks over which the patient may suffer several consequences and below are some of the most common errors.

1.  Unpredictable bioavailability:  When drugs pass through the gastrointestinal tract, they are exposed to various enzyme systems and they are partly metabolized by the liver enzymes.  Also, some foods that we take may hinder proper absorption of some drugs.

2.  Induction of Nausea and vomiting:  The oral route of drug administration is one of the most triggers of nausea and vomiting and almost more than 90% of the drugs taken via this route, have a potential to induce vomiting.  This is because the vomiting center in the brain has some receptors in the gastrointestinal tract.

RELATED;

1.  FUNCTIONS OF THE LIVER

2.  BIOAVAILABILITY

3.  THE INTRAVENOUS ROUTE

4.  PHARMACOLOGY AND MEDICATIONS

BURNING AND IMAGE MANAGEMENT SOFTWARE DOWNLOADS

BURNING AND DISC MANAGEMENT SOFTWARES:  On this page, get access to some of most dependable burning and image managing software.  These software can be used to burn disc images, create bootable flash discs and converting different media files to various formats.

1.  Ashampoo burning studio 2010 + serial key 

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4.  Express burn setup  

5.  Windows DVD maker:  Windows DVD marker is a basic movie marker software based on windows 7, with easy to use interface that can be used to create slideshows and compiling movies for DVD burning.

RELATED;

1.  ULTIMATE WINDOWS SOFTWARE DOWNLOADS

2.  SOFTWARE DOWNLOAD LINKS

HOW TO WRITE A RESEARCH REPORT

HOW TO WRITE A RESEARCH REPORT:  Submission of a research report, is a requirement in partial fulfilment for the award of degrees and diplomas in different medical specialties and institutions.  A research report is the final workout of the medical research project.  Now we are taking it that you already finished collecting, analyzing and presenting data, and that data is now compiled, ready to be put in the report. At this point, I am also assuming that you have liaised with your supervisor who have fully accepted your research methodology and data analysis techniques, and given you a go a head with the next step of your research project.  We have already discussed much about the research methodology and the roles of a research supervisor in a research project as you can read about them in the links below;

1.  Roles of a research supervisor

2.  The research methodology

We have already seen that we had three chapters in the research proposal, and now, we are adding more three chapters to make it to six chapters in the research report.  So at this point, we are looking at Chapter one, Chapter two, Chapter three, four, five and six.  If you have not been following us, follow the link below for the component of a research proposal.

Components of a research proposal 

In this article, we are looking at the steps taken and component of a medical research report.  As we have had Chapter one, two and three in the proposal, they will remain in the report and the only change that we are putting in is that now we have finished doing all we promised in the proposal.  And so, we shall be addressing all we did in a past tense.  Let's take an example if one said in methodology "I will use village health team members from all the parishes selected"  The statement will now be;  "I used village health team members from all the parishes I had selected".

RELATED;

1.  DATA ANALYSIS

2.  COMPONENTS OF A RESEARCH REPORT

3.  HOW TO WRITE A RESEARCH PROPOSAL

REFERENCES

GINSENG AND CARDIOVASCULAR DISEASE

INTRODUCTION: Ginseng is one of the oldest known herbal remedies. Panax ginseng is distributed throughout China, Korea, and Siberia, whereas Panax quinquefolius is native to Canada and the United States. There are differences in chemical composition between the two species of ginseng; American ginseng is not considered equivalent to Siberian ginseng. The plant’s popularity has led to its extinction from certain regions, and much of the commercial ginseng is now grown commercially. Ginseng has been used for centuries to promote general wellness, boost immune function, increase mental performance, and reduce fatigue. Immunity: Mental conditions

There are some claims that the herb lowers blood glucose in patients with type 2 diabetes and can help in the management of erectile dysfunction. Diabetes: Electiledysfunction drugs

Ginseng is thought to have calcium channel antagonist actions. The herb may improve blood flow to the heart in times of low oxygen supply, such as with myocardial ischemia.

RELATED;

1.  GARLIC FOR CARDIOVASCULAR CONDITIONS  

2.  HEART FAILURE

3.  CARNITINE AND MANAGEMENT OF HEART DISEASES

REFERENCES

OBESITY

INTRODUCTION: Morbid obesity is the term applied to people whose body weigh more than twice their ideal body weight, or those whose body mass index (BMI) exceeds 30 kg/m2. BMI is the patient’s weight in Kgs divided by the patient’s height in metres squared. Patients with morbid obesity are at higher risk for health complications, such as diabetes, heart disease, stroke, hypertension, gallbladder disease, osteoarthritis, sleep apnea and other breathing problems. Diabetes: Stroke: Hypertension

Such patients are also prone to some forms of cancer including but not limited to; uterine, breast, colorectal, kidney, and gallbladder neoplasms. They frequently suffer from low self-esteem, impaired body image, and depression.

MEDICAL MANAGEMENT: A weight loss diet in conjunction with behavioral modification and exercise is usually unsuccessful.

Pharmacologic Management:  Sibutramine HCl decreases appetite by inhibiting the reuptake of serotonin and norepinephrine. Orlistat reduces caloric intake by inhibiting digestion of triglycerides. multivitamin is usually recommended. Rimonabant blocks the cannabinoid-1 receptor that is thought to play an important role in some aspects of human metabolism, including obesity.

SURGICAL MANAGEMENT: Bariatric surgery (surgery for morbid obesity) includes gastric restriction procedures such as gastric bypass and vertical banded gastroplasty (performed laparoscopically or by open surgical technique). Body contouring after weight loss involves lipoplasty to remove fat deposits or a panniculectomy to remove excess abdominal skinfolds.

RELATED;

1.  METABOLISM AND METABOLIC DISORDERS

REFERENCES

ANDROID FLASH TOOLS

 

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1.  ANDROID-WINDOWS CONNECTIVITY

2.  FULL LIST OF FASTBBOOT COMMANDS

3.  MEGA MOVER EMPIRE TRENDS

WINDOWS ACTIVATOR

 

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1)  Make sure you are offline, so disconnect your PC from any kind of internet supply.

2)  Temporarily turned off your antivirus installed on your PC.  In case you are using windows 10 and higher, temporarily turn off Windows defender as well.  There is a video demonstration on that following the link below.

How to temporarily turn off Windows defender

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Winrar for windows 10 x64

You can as well download it from the official site basing on the type of OS you are running.  After downloading Winrar, download the activator from the link provided below and go a head to actvate your windows.  After unzipping the download, you will notice there is a setup in the folder just run the installer and the steps will be automatic and simple.  Then after restart your PC and then you can switch back your antivirus software once you note your Windows are now activated.

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RELATED;

1.  WINDOWS SOFTWARE DOWNLOADS

2.  ULTIMATE SOFTWARE DOWNLOADS

3.  WINDOWS-ANDROID CONNECTIVITY

4.  MEGA MOVER EMPIRE ON YOUTUBE

PROTEIN–ENERGY MALNUTRITION [PEM]

Introduction:  It is the most widespread nutritional problem in developing countries; predominantly affecting children.  The prevalence rate varies from 20-50% in different areas depending on socioeconomic status and level of education and awareness.

Spectrum of the condition:  At one end of the spectrum of malnutrition is marasmus, which results from a continued severe deficiency of both dietary energy and proteins (primary calorie inadequacy and secondary protein deficiency).  At the other end of the spectrum is kwashiorkor, where isolated deficiency of proteins along with adequate calorie intake is seen.  A classification by WHO is based on body weight as a percentage of standard body weight.

Manifestations:  The hallmarks of kwashiorkor are hypoalbuminemia, which stands for lower than recommended plasma proteins specifically Albumin.  Albumin values less than 2 g/dl is a biochemical marker in cases of kwashiorkor.  There is also poor wound healing and edema.  In marasmus, this may not be so low.  However, IgG increases due to associated infections.  Fatty liver is seen in some cases of kwashiorkor, but not in marasmus.  Fatty liver is due to decreased lipoprotein synthesis.  Glucose tolerance is often normal, but hypoglycemia may be seen in marasmic children.  Hypokalemia and dehydration may be seen when there is diarrhea.  Hypomagnesemia is a usual finding.

Treatment of Protein Energy Malnutrition:  Optimal response is observed with diets providing 150-200 kcal/kg body weight and 3-4 g of protein/kg body weight. A mixture of three parts of vegetable proteins (Bengal gram or peanuts) and one part of milk protein is found to be very effective.  It is monitored by disappearance of edema, rise in serum albumin level and gain in weight.

Sequelae of Protein Calorie Malnutrition:  Severe malnutrition in early life can lead to permanent and irreversible physical and functional deficits.  Severe persistent malnutrition may have deleterious effects on the intellectual capacity in later life.  There may not be any sequelae where the moderate and mild forms are corrected in time.  Since the children of today are the force of tomorrow, a nationwide effort is to be made to eradicate childhood malnutrition.

RELATED;

1.  METABOLISM AND METABOLIC DISORDERS

2.  PROTEINS

3.  METABOLISM AND HOMEOSTASIS

4.  BIOCHEMISTRY

REFERENCES