Natural Whitening Agents

The male eyes never fail to spot a beautiful woman. Men admire beauty in women. Female beauty lies in fair skin, beautiful hair, slim figure, and higher than average stature. Beauty matters most for men. The cosmetic industry has moved into screening for natural sources of ingredients that can make human skin appear fairer. 

The melanin production system (melanogenesis) is buried under the skin, in the dermis. So topical agents will suffice to give fair skin. If black skin can turn to white, there is no stopping at what the cosmetic industry can do for the skin. The core of looking fair or white is the melanin pathway. Knowing how it is constructed and how it functions, gives the researcher a good feel at what to target when making cosmetic products. Tyrosinase is the enzyme responsible for making our skin dark and very dark. Without tyrosinase, we are albinos. So tyrosinase inhibitors are what we are looking for in natural sources. We are looking for regulators or inhibitors of melanin production.

Superoxide dismutase (SOD) is another enzyme that reduce melanin production caused by UV radiation. This is important for people who live in the mountains and have high exposure to UV radiation and thefore develop dark skin.

Chronic UV exposure denatures collagen and elastic fibers in the dermis and induces wrinkles in human skin. In the process of photoaging of human skin, neutrophils play an important role. They infiltrate the skin and release active enzymes such as human leukocyte elastase (HLE), which cleaves the helix structure of type I collagen and then degrades elastic fibers in human skin. Therefore, HLE inhibitors may be useful ingredients for prevention of skin wrinkles.

The ancient Chinese have tabulated over 200 herbal formulas which can make the women's face beautiful. 

Plants from the genus Umbelliferae, Ericaceae, Rubiaceae, Piperaceae and Rutaceae have been screened by Japanese researchers.

Things to look for in herbal extracts (leaves, roots, rhizomes, seeds, stems, fruits, barks, etc):

1. tyrosinase inhibitory activity 
2. anti-oxidant activity 
3. HLE inhibitory activity

Source:

InTech-Melanin_hyperpigmentation_inhibitors_from_natural_resources.pdf

skin-whitening-herbs

papaya soaps

good skin

funny pics

Polyol pathway in diabetic nephropathy

Aldose reductase (polyol formation) pathway

1. The polyol pathway involves two enzymatic reactions.
2. The first is the reduction of glucose to sorbitol by the action of aldose reductase.
3. The second is the oxidation of sorbitol to fructose by the action of sorbitol dehydrogenase. 
4. In the aldose reductase reaction, NADPH is oxidised to NADP+ as glucose is converted to sorbitol.
5. NADP+ is converted back to NADPH by the pentose phosphate pathway (PPP).
6. PPP contributes to the triose phosphate pool.
7. In the sorbitol dehydrogenase reaction, NAD+ is reduced to NADH as sorbitol is reduced to fructose. 
8. High NADH:NAD+ ratio inhibits formation of 1,3-BPG (or 1,3-DPG).
9. http://en.wikipedia.org/wiki/Polyol_pathway
10. Also called the sorbitol-aldose reductase pathway.

Complications of diabetes: Diabetic nephropathy 

1. The polyol pathway appears to be implicated in diabetic complications, especially in microvascular damage to the retina, kidney, and nerves.
2. In diabetic renal complications, hyperglycemia may cause damage at a cellular level in both glomerular and tubular locations, often preceding overt dysfunction.
3. Sorbitol cannot cross cell membranes, and, when it accumulates, it produces osmotic stresses on cells by drawing water into the insulin-independent tissues, resulting in oedematous tissues.

Aldose reductase and the role of the polyol pathway in diabetic nephropathy

A possible cause of hyperfiltration and glomerular dysfunction in diabetes is: aldose reductase-induced use of nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) drives the pentose phosphate pathway, which culminates in a protein kinase C–induced increase in glomerular prostaglandin production and loss of mesangial cell contractility.

In diabetes, hyperglycemia-induced renal polyol pathway activity does not occur in isolation but instead in tandem with oxidative changes and the production of reactive dicarbonyls and ,-unsaturated aldehydes. Aldose reductase may detoxify these compounds.

In renal mesangial and proximal tubule cells, the accumulation of sorbitol can be demonstrated by elevated glucose concentrations; its accumulation has been proposed as a mechanism for altered cellular myoinositol level and reduced Na+/K+-ATPase activity, each with a potentially detrimental effect in diabetes. However, in the cells of the inner medulla, sorbitol may function, together with betaine and glycerophosphorylcholine, as part of the organic osmolyte defense against extracellular solute fluctuations.

Fructose

Fructose, the second product of polyol pathway is increased several fold in tissues with an activated polyol pathway and can contribute to nonenzymic fructosylation of proteins and provide 3-deoxyglucosone, the precursor to advanced glycation end products (AGEs).

After formation of polyol pathway products, important alterations in the ratio of reduced pyridine nucleotides result from flux through the polyol pathway.

Sorbitol

Reduction of glucose to sorbitol uses NADPH and oxidation of sorbitol increases NADH with a resultant rapid change in the cytoplasmic redox state. Decreased NADPH (altered cytosolic ratio of NADPH:NADP+) may compromise reduction of glutathione in oxidatively stressed cells. Increased formation of NADH, following oxidation of sorbitol to fructose, favors a condition of hyperglycemia-induced pseudohypoxia in diabetic tissue whereby abnormalities accompanying the increase in the ratio of NADH:NAD+, without a decrease in pO2, bear close parallels to the effects of true hypoxia on vascular function.

NADPH:NADP+ ratio; NADH:NAD+ ratio; PPP

Increased use of NADPH by activity of aldose reductase could alter cellular metabolism in several ways, consequent in part on the stimulation provided to the pentose phosphate pathway. As the oxidative reactions of the pentose phosphate pathway are inhibited by NADPH, its consumption in aldose reductase–activated conversions provides the conditions for a constant throughput of glucose to provide pentose phosphate pathway intermediates. Flux through the pentose phosphate pathway may be favored further if an increased NADH:NAD+ ratio inhibits the NAD+-requiring enzyme glyceraldehyde-3-phosphate dehydrogenase, preventing 1,3-bisphosphoglycerate formation from glyceraldehyde-3-phosphate in glycolysis.

Diagram

These pathways are summarized in Figure 1. In part, activation of the pentose phosphate pathway supplies the increased requirements for ribose 5-phosphate and NADPH for biosynthetic reactions occurring with renal hypertrophy in experimental diabetes.

Polyol pathway in hyperglycaemia

The effect of the polyol pathway on pyridine nucleotide flux and metabolism of glucose. The metabolism of glucose to sorbitol and fructose in the polyol pathway by aldose reductase (AR) and sorbitol dehydrogenase (SDH), respectively, alters cytosolic pyridine nucleotides to provide an increased ratio of NADP+/NADPH and NADH/NAD+. Utilization of NADPH provides conditions for sustained action of the pentose phosphate pathway (PPP) whereas use of NAD+ may inhibit formation of 1, 3 bisphosphoglycerate (1,3 BPG) from glyceraldehyde-3-phosphate resulting in an increased triose phosphate pool. HK, hexokinase.

Source:
Kidney International. Direct Effects Of High Glucose. Available at: http://www.nature.com/ki/journal/v58/n77s/fig_tab/4491969f1.html#figure-title (Accessed 30 May 2013)

Citation:
Marjorie Dunlop. Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney International (2000) 58, S3–S12; doi:10.1046/j.1523-1755.2000.07702.x

Correspondence:
Marjorie Dunlop, Ph.D., University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia. E-mail: m.dunlop@medicine.unimelb.edu.au

Fasting

Fasting is important in medicine and medical teaching. Fasting is different from non fasting. The blood contents are different when we fast. Why?

To answer the question, we first need to know which pathways are active during fasting, then we can try and answer "Why".

What pathways are active during fasting?

1. Glycogenolysis (this happens initially because glycogen stores are very limited)
2. Protein breakdown (from the skeletal muscles that help us move)
3. Fat mobilisation (after day 3 of fasting)
4. Beta-oxidation (when the fatty acids enter liver mitochondria, to yield acetyl CoA)
5. TCA cycle (to yield NADH and FADH2)
6. Oxidative phosphorylation (ETC process, to yield ATP)

Explanation:

1. Blood glucose is reduced during fasting. So alternative sources of energy need to be sought or found by the body. Remember, our body is "intelligent" - it knows where to look for energy sources, without complaining to us.
2. Glycogen is broken down to yield glucose (refer to glycogenolysis lecture notes).
3. Blood amino acids maybe initially increased and then reduced during fasting. The body has to use its protein stores first, i.e., mainly using our muscles - our biceps, triceps, etc. When our muscles are broken down to yield amino acids, we feel weak as we lose muscle (which is protein) and usually we cannot be as strong and energetic when we fast as our muscles are partially used to supply us energy.
4. Blood fatty acids are elevated during fasting as fat mobilisation occurs. That means the body tries to breakdown its fat stores (from adipose tissues), leading to high fatty acids in the blood. These fatty acids are hydrophobic molecules (do not mix with water) and travel by way of albumin (transporter molecule) to the liver, where they undergo beta-oxidation. Refer to beta-oxidation lecture notes. Beta-oxidation has 4 steps and yield acetyl CoA (which is a 2C unit), which enters TCA cycle, and the products (NADH, FADH2) enter ETC, to yield ATP by oxidative phosphorylation. ATP is the energy we get and during fasting, it is derived from mobilised fats. This source of energy is good starting on day 3 onward, that's when fats are mobilised, till we end fasting, usually one month as in Ramadan fasting. Fat stores are the last to be used, and only after day 3 do we start using fats. So if we fast less than 3 days, fat stores are not used, and we don't hope to lose weight or fat by fasting less than 3 days. How is fat mobilised? Refer to your lipid mobilisation lecture notes. There is a hormone called HSL (hormone sensitive lipase) that is activated by cyclic AMP (c-AMP). HSL acts on TG and breaks it down to DG and further to MG and lastly to glycerol (G) and free fatty acid (FFA). So HSL is a fat buster and breaks down fat step-by-step (i.e., stepwise, like a cascade).

External links:

https://www.youtube.com/watch?v=h2CT4Y13kaU

Acromegaly: Signs and Symptoms - Skin tags

http://en.wikipedia.org/wiki/Acromegaly
http://en.wikipedia.org/wiki/Acrochordon

Skin Tags

An acrochordon (plural acrochorda, and also known as a (cutaneous) skin tag, or fibroepithelial polyp) is a small benign tumor that forms primarily in areas where the skin forms creases, such as the neck, armpit, and groin. They may also occur on the face, usually on the eyelids.

Acromegaly: Glucose Suppression Test

Glucose Suppression Test - for Growth Hormone secretory dynamics
http://ccpd.ucsf.edu/oral_glucose.shtml

Indication:

1. The oral glucose tolerance test is used for the diagnosis of acromegaly and to determine remission after surgery.
2. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of carbohydrate metabolism.

Interpretation:

1. In normal individuals, hyperglycemia suppresses growth hormone secretion.
2. In normal individuals, glucose suppresses below 2 ng/ml after ingesting 100g of glucola.
3. More sensitive assays require a growth hormone level below 1 ng/ml to rule out acromegaly.

Caution:
False positive results can occur in patients with diabetes mellitus, anorexia, liver failure, tall adolescents and individuals with growth hormone resistance disorders.
External links
http://en.wikipedia.org/wiki/Acromegaly

USM New Medical Students Interview 10-11 May 2013

The new medical students interview was held on 10 & 11 May 2013 at BPSP, USM in Kubang Kerian, Kelantan. It rained heavily at night after the first interview. May is a rainy season in Kelantan. There were altogether 526 interviewees.

This is feedback from the chief secretariat that organised the interview for the new medical students:

Bagi pihak urusetia Pengambilan Pelajar PPSP sesi 2013/2014, saya mengucapkan setinggi-tinggi penghargaan kepada semua penemuduga yang telah mengambil bahagian dalam proses temuduga yang telah berlangsung pada 10 dan 11hb Mei lepas.

Kami amat menghargai komitmen yang telah ditunjukkan termasuk beberapa penemuduga yang telah secara sukarela membantu pada hari kedua.

Saya juga mengucapkan setinggi-tinggi penghargaan kepada semua ahli urusetia yang telah menjayakan proses tersebut.

Seramai 526 calon telah berjaya ditemuduga.

Dr. Ahmad Fuad bin Abdul Rahim
Jabatan Pendidikan Perubatan
Pusat Pengajian Sains Perubatan
Universiti Sains Malaysia Kubang Kerian

Our medical school can only accept 150 students. The lecture halls also fit that many. When we divide 150 students into small groups, we get 15 groups of 10 students for small group discussion (SGD). In my department, we are left with 8 lecturers (from initial 12) since many have retired or moved elsewhere. So two SGD groups will need to break up and the students have to seek other groups to join for SGD. It becomes messy and students end up unhappy. Lecturers also become unhappy as a 'small group' is now a 'big group'. Sometimes lecturers have other commitments and the SGD groups have to be combined and taken as a big class lecture-discussion by one or two lecturers who are around.

Lipid Metabolism - Fatty acid synthesis

I have covered lipid metabolism and fatty acid synthesis. I mentioned the following statements:

Recall

1. Fatty acid synthesis occurs in the cytosol (as opposed to nucleus or mitochondria).
2. Acetyl CoA carboxylase (ACC) is a part of the large multienzyme fatty acid synthase complex.
3. ACC is responsible for producing malonyl CoA, the first step in fatty acid synthesis. 
4. Fatty acid synthesis requires 2 things - acetyl CoA and NADPH.
5. Where do acetyl CoA and NADPH come from?
6. Acetyl CoA comes from the Kreb cycle, from the mitochondrial matrix
7. NADPH comes from the pentose phosphate pathway (PPP).
8. Acetyl CoA needs to exit the mitochondria and enter into the cytosol, where fatty acid synthesis can then occur.
9. More two-carbon (2C or C2) units are added in subsequent steps, till the fatty acyl chain has 16 carbons (16C), which is palmitic acid (C16:0). Palmitic acid has no carbon double bonds (C=C) because it is a saturated fatty acid. Only palmitic acid is formed.

Reading

Please read this scientific journal article at NIH Public Access:
Michael J. MacDonald, Agnieszka Dobrzyn, James Ntambi, and Scott W. Stoker
Arch Biochem Biophys. 2008 February 15; 470(2): 153–162.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453002/pdf/nihms40601.pdf

Pancreatic beta cell mitochondria convert insulin secretagogues into products that support insulin exocytosis. We explored the idea that lipids are some of these products formed from acyl group transfer out of mitochondria to the cytosol, the site of lipid synthesis. There are two isoforms of acetyl-CoA carboxylase, the enzyme that forms malonyl-CoA from which C2 units for lipid synthesis are formed. We found that ACC1, the isoform seen in lipogenic tissues, is the only isoform present in human and rat pancreatic islets [...]. Inhibitors of ACC and fatty acid synthase inhibited insulin release in islets [...]. Carbon from glucose and pyruvate were rapidly incorporated into many lipid classes in INS-1 cells. Glucose and other insulin secretagogues acutely increased many lipids with C14-C24 chains including individual cholesterol esters, phospholipids and fatty acids. Many phosphatidylcholines and phosphatidylserines were increased and many phosphatidylinositols and several phosphatidylethanolamines were decreased. The results suggest that lipid remodeling and rapid lipogenesis from secretagogue carbon support insulin secretion.- MacDonald et al, ABB 2008, 470(2):153-162.

Further study notes

1. There are 2 isoforms of ACC.
2. Lipogenic tissues contain ACC1 isoform.
3. ACC1 is found in human and rat pancreatic islets.
4. Inhibitors of ACC and fatty acid synthase inhibited insulin release in pancreatic islets.
5. Glycolysis: each glucose molecule has 6 carbons; each pyruvate molecule has 3 carbons.
6. Carbon (C) from glucose and pyruvate were rapidly incorporated into many lipid classes.
7. Glucose and other insulin secretagogues increased C14-C24 lipid chains in 3 lipid classes - cholesteryl esters, phospholipids and fatty acids.
8. Comparing the 4 phospholipids (PLs) classes, many phosphatidylcholines (PCs) and phosphatidylserines (PSs) were increased and many phosphatidylinositols (PIs) and several phosphatidylethanolamines (PEs) were decreased.
9. Triglyceride (TG) synthesis shares the same pathway (at some point) with phospholipid synthesis.
10. Diphosphatidate can go to form either TG or PL. 

Further questions

1. Where are the other fatty acids (C14, C12, C10, C8, C4) formed?
2. Are any of them important?