Peristalis Movement

Peristalis Movement is a reflex response that is initiated when the gut wall is stretched by the contents of the lumen
A contractile ring appears around the gut and then moves forward
Peristalsis is an inherent property of many syncytial smooth muscle tubes;
The usual stimulus for intestinal peristalsis is distention of the gut.

BIOSYNTHESIS of Catecholamines

Overview
- biosynthesis of catecholamines is done in 3 (4) steps

TYROSINE
      | tyrosine hydroxylase
DOPA
      | DOPA decarboxylase
DOPAMINE
      | dopamine beta-hydroxylase
NORADRENALINE
      | phenylethanolamide N-methyltransferase (“PNMT”)
ADRENALINE
- , thus there are 3 (4) enzymes involved in catecholamine biosynthesis

ENZYME NAME

DESCRIPTION



TYROSINE HYDROXYLASE

- the rate-limiting step
- located in the cytoplasm of sympathetic postsynaptic neurons

DOPA DECARBOXYLASE

DOPAMINE BETA-HYDROXYLASE
PNMT

- general enzyme located in the cytoplasm of most cells
- catalyses decarboxylation of aromatic amino acids
- located in the synaptic vesicles of postsynaptic sympathetic nerve terminals
- located in the a-cells of the adrenal medulla

Relevant Drugs
- 3 types

DRUG NAME

DESCRIPTION



ALPHA-METHYLTYROSINE

METHYLDOPA

General information
- a tyrosine hydroxylase inhibitor
- inhibits tyrosine hydroxylase, thus causing inhibition of catecholamine synthesis
Clinical use
- treatment of pheochromocytoma (a catecholamine-
producing adrenal medullary tumor)
Side effects
- hypotension (due to vasodilation)
- drowsiness
General information
- a central DOPA decarboxylase inhibitor (may cross the blood-brain barrier)
- alternate substrate for DOPA decarboxylase , thus displacing DOPA from the active site of DOPA decarboxylase and following inhibition of catecholamine synthesis
- is converted by DOPA decarboxylase to methylnoradrenalin (a selective alpha-2 agonist, see 19)
Clinical use
- treatment of hypertension during pregnancy (by
inhibition of the sympathetic nuclei of the brainstem)
Side effects
- same as alpha-methyltyrosine (see above)

CARBIDOPA
- impotency
- hypersensitivity reactions
General information
- a peripheral DOPA decarboxylase inhibitor (may not
pass the blood-brain barrier)
Clinical use
- treatment of parkinson’s disease (by inhibition of the
use of DOPA for catecholamine synthesis in
peripheral neurons, thus freeing it for restorement of
 the dopaminergic pathways of the brain
 

Japan’s Earth Quake and Tsunami is the costliest Natural disaster!!!

The Japanese government on Wednesday estimated the direct damage from a deadly earthquake and tsunami that struck the country's northeast this month at as much as $310 billion, making it the world's expensive natural disaster.

The first official damage estimates will serve to map out disaster relief plans and emergency budgets to fund recovery costs.

Tokyo said the estimate covered damage to roads, homes, factories and other infrastructure, and eclipses the losses incurred by other natural disasters such as the 1995 Kobe quake and Hurricane Katrina in 2005.

The figure could go even higher, as the estimate does not include losses in economic activity from planned power outages or the broader impact of a crisis at a stricken nuclear power plant in Fukushima, which economists say pose the biggest risks to the economy.

"The impact from the planned power outages is likely to be significant," Fumihira Nishizaki, director of macroeconomic analysis at the Cabinet Office told reporters.

The upper end of the 16-25 trillion yen ($197-308 billion) estimate range would amount to about 6 percent of Japan's gross domestic product.

"This quake will cause the condition of Japan's economy and output to be severe," Bank of Japan Governor Masaaki Shirakawa told a parliamentary committee.

Speaking separately, central bank board member Ryuzo Miyao repeated the bank's pledge to take appropriate policy action if needed to support the world's third-largest economy.

"We need to be mindful that the quake's negative impact on the economy, at least on the supply side, may be bigger than the Kobe quake 16 years ago, and be prolonged," he added.

In its initial response to the disaster, the central bank doubled the funds earmarked for purchases of a range of assets and started pumping record amounts of cash into the money market to prevent it from seizing up.

It later followed up by joining forces with other G7 central banks in a rare coordinated move to keep a rallying yen from inflicting further damage to the economy.

Introduction to GI physiology

Lies in the wall of the gut, beginning in the esophagus and extending all the way to the anus.

no of neurons in this enteric system is almost exactly equal to the no in the entire spinal cord (100 million)

The enteric nervous system is composed mainly of two plexuses

myenteric plexus or Auerbach’s plexus, and the submucosal plexus or Meissner’s plexus, that lies in the submucosa.

Myenteric plexus

consists mostly of a linear chain of many interconnecting neurons.

is concerned mainly with controlling muscle activity along the length of the gut

Stimulation of the plexus causes

↑ed tonic contraction, or “tone,” of the gut wall,

↑ed intensity of the rhythmical contractions,

slightly ↑ed rate of the rhythm of contraction, and 

↑ed velocity of conduction of excitatory waves along the gut wall, causing more rapid movement of the gut peristaltic waves.

Submucous

the submucous plexus innervates the glandular epithelium, intestinal endocrine cells, and submucosal blood vessels.

primarily involved in the control of intestinal secretion

neurotransmitters: acetylcholine, the amines norepinephrine and serotonin, the amino acid GABA, the purine ATP, the gases NO and CO, and many different peptides and polypeptides.

The parasympathetic supply to the gut is divided into cranial and sacral divisions

cranial fibers provide extensive innervation to the esophagus, stomach, and pancreas and somewhat less to the intestines

Sacral division innervates the distal half of the large intestine and all the way to the anus.

parasympathetic cholinergic activity generally increases the activity of intestinal smooth muscle

Teej Festival of nepali hindu women where song and dance is essential!!!!!!!!!

Teej (Nepali: तीज) also known as Haritalika  Teej is a fasting festival for Hindu women. It takes place in 3rd day of Shukla Paksha in Bhadrapada or Bhadra month of  Nepali calendar and Hindu calendar, normally falls in the month of August or early September. Dedicated to the Goddess Parvati, commemorating her union with Lord Shiva, the festival is celebrated for marital bliss, well-being of spouse and children and purification of own body and soul. The festival is a three-day-long celebration that combines sumptuous feasts as well as rigid fasting. Teej have other importance as women create  new songs about recent happening and  throw shutire over  males specially who dominate over their husband and daughter in laws.

Preparations for the festival begin well in advance. Fabric stores, sarees and suit outlets are stocked with the bridal red color fabric. Women spend most of the time shopping when Teej is near. Women mainly shops for golden ornaments, new clothes specially red one, bangles etc. Teej gives women an opportunity to dress like the newly wed. They worship the epitome of divine marriage - Lord Shiva and Goddess Parvati, for longevity and prosperity for their husband and family.

 Teej in Nepal is celebrated in three days. The first day of Teej is called Dar Khane Din. On this day the women, both married and unmarried, gathered together in a place and dance in special folk songs called teej song and eat delicious foods. In remote areas the married women goes at her mother’s place and dance and eat there.

     The second or the fasting day of the Teej festival is dedicated to pujas and prayers. The holy Pashupatinath temple is thronged by women in red sarees to offer prayers to Lord Shiva. Women gather in the temple and circumambulate the Lingam (phallic symbol of the Lord) adorned with flowers, sweets and coins. The beautifully decorated idols of Shiva and Parvati are offered fruits and flowers to seek blessings of the divine spirits. Lighting of an oil lamp is very important part of the puja ceremony. It is said that the oil lamp should be kept lit all night to avoid bad omen.   

The third day of the Teej Festival is called Rishi Panchami. On this day, the seven sages of the Hindu pantheon are worshiped by women in a belief that it will cleanse all sins of the previous year. Womenfolk take a holy bath with red mud found on the roots of the sacred Datiwan bush, along with its leaves. After three hours of rigorous cleansing, they come out purified and absolved from all sins. After this they sit in a semicircle while a priest sitting in the middle chants devotional prayers.

Gluconeogenesis

Substrate  for  gluconeogenesis  :
pyruvate
Lactate
Glycerol
Propionate
Glucogenic  aminoacids


Tissue  location :
Mainly  in  the  liver
Lesser  extent  in  renal  cortex

Intracellular  location :
  - partly  mitochondrial
  -  partly  cytsolic

Significance  of  gluconeogenesis :

  - maintains  blood  glucose  level

 -  Clears  up  the metabolites  like  lactate, glycerol etc.

Gluconeogenesis  from glucogenic aminoacids

The Cori Cycle  (Lactic acid cycle)

Treatment of peptic ulcer

Gastric/duodenal

• Mucosal defensive factors- mucus, mucosal blood blow, formation of HCO- 3 and PGE  2   & PGI2
• Aggressive factors- acid, pepsin, NSAIDs, H. pylori
• 
  
• Physiology of HCl secretion
• Gastric parietal cells have receptors for gastrin (from antral G cells), histamine (from ECL cells), acetylcholine ( from vagal efferents) and prostaglandin (PGE2 & PGI2- from gastric mucosa)
• Enterochomaffin-like cells histamine
• 
  
• 
  
• Stimulation of H2 receptors by histamine activation of adenyl cyclase  increase in cAMP activation of protein kinases stimulates H+ secretion from H+  /K+ ATPase (proton pump- final step) into the canalicular surface, H+ combines with Cl to form HCl  gastric lumen
• 
  
• Activation of M3 by Ach and gastrin receptors activation of phoshpolipase C IP3-DAG increase in cytosolic Ca++  activation of protein Kinases stimulation of  H+ secretion from H+  /K+ ATPase (proton pump) 
• 
  
• Stimulation of PG receptor by PGE2  inhibits cAMP in parietal cells and Gastrin release from antral cells decrease in HCl secretion
• 
  
• PGE2 also increases mucosal blood flow and mucus and HCO3 secretion cytoprotective effect
• 
  
• So, H2 antagonists, proton pump inhibitors, anticholinergics, HCl neutralizing agents and H Pylori inhibiting agents are the anti-ulcer drugs
• Also, ulcer protective and ulcer healing agents

Classification

I. Drugs which reduce gastric acid secretion

A. H2 receptor antagonists (H2antihistaminics) -cimetidine, ranitidine, famotidine, roxatadine, loxatadine

B. Proton pump inhibitors- omeprazole, lansoprazole, pantoprazole, rabeprazole

C. Anticholinergics- propanthelin, pirenzepine, telezepine

D. Prostaglandin analogs- misoprostol (PGE1), enprostil (PGE2), rioprostil (PGE1)

II. drugs which neutralize gastric acid (antacids)

A. systemic- sodium carbonate

B. non-systemic aluminium hydroxide, aluminium phosphate, magnesium trisilicate, megaldrate, magnesium hydroxide, calcium carbonate

III. Ulcer protective- sucralfate, colloidal bismuth subcitrate

IV. Ulcer healing drugs- carbenexolone sodium

V. Anti H pylori drugs (used in combination)

 amoxicillin, clarithromycin, metronidazole, tinidazole, tetracycline 

I. Drugs which reduce gastric acid secretion

A. H2 antagonists

MOA-  block H2 histaminic receptors  in gastric parietal cells ↓ HCl secretion

Cimetidine

ADR- 

Headache, GI upset

Antiandrogenic effect (displaces dihydrotestosterone from the receptor), ↑prolactin gynecomastia, loss of libido, impotence, decrease in sperm count

•Inhibits cytochrome P450– inhibits the metabolism of theophylline, sulfonul ureas, warfarin, mexiletineà toxicity

•Bolus IV injection à histamine releaseà bradycardia, arrhythmias and cardiac arrest

•CNS effects- hallucinations, delirium, convulsion and coma

Uses-

Duodenal ulcer – 400mg bid, or 800 mg hs for 8 weeks

Gastric ulcer

Stress ulcer and gastritis

Zollinger –Ellison syndrome (gastric hypersecretory state)

Dietary & mucosal proteins are also adsorbed to this coat which form another layer & provides further resistance to the  ulcer base so that aggressive factors (acid, pepsin) don’t come in contact with the ulcer base

Also increases mucosal PGE2 synthesis and HCO3 formation
Stimulates epithelial & fibroblast growth factor promotes healing

Caesarean delivery (C-section)

Functioning of Nephron

A nephron (from Greek νεφρός (nephros) meaning "kidney") is the basic structural and functional unit of the kidney. Its chief function is to regulate water and soluble substances by filtering the blood, reabsorbing what is needed and excreting the rest as urine. Nephrons eliminate wastes from the body, regulate blood volume and pressure, control levels of electrolytes and metabolites, and regulate blood pH. Its functions are vital to life and are regulated by the endocrine system by hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

Reference:

1. http://en.wikipedia.org/wiki/Nephron

With home crowd support, Azkals expect tight match vs Nepal

Nepal

0 0 Yet to be Played 11-Oct-2011 04:45 PM NST Rizal Memorial Stadium, Manila

Philippines

 For Team Updates Click  here

For Live Game Click Here

For Live Minute to Minnute Updates Click Here

Therapy of Diarrhoea

• Absorption of ions:
• Cl-, HCO3- absorption is passive 
• HCO3- is also exchanged for Cl-
• Bicarbonate (accompanied by Na+) absorbed secretion of H+.
• K+ excreted by exchanging with Na+, also excreted by secretion to mucus.
• 
  
• Secretary process stimulated by PGs and intracellular Ca2+
• All acute enteric infections produce secretary diarrhoea. 
• Accumulation of cGMP caused by the heat stable toxin of Clostridium difficale and E. Histolytica
• enhances anion secretion.
• Carcinoid diarrhoea mediated by cAMP
• Bile acids case diarrhoea by activating adenylyl cyclase. 
• Hyper motility of bowel now considered to be ofsecondary role in diarrhoea.

Rational Of ORS

For more than 25 years, WHO and UNICEF recommended a single formulation of glucose-based

Oral Rehydration Salts (ORS) to prevent or treat dehydration from diarrhoea irrespective of the cause or age group affected.

Standard formula recommended was:

Nacl      60 mM (3.5 gm)

KCl      20 mM (1.5 gm)

Trisodium citrate    30 mM (2.9 gm)

Glucose     110mM (20 gm)

to be dissolved in   1 litre of water

Drug therapy

Antimicrobials:

Antimicrobials have limited role in overall treatment of diarrhoeal patients. 

Antimicrobials are of no value in diarrhoea due to non infective cases such as:

1.IBS

2. Coeliac disease 

3. Pancreatic enzyme deficiency

4. Topical sprue

5. Thyrotoxicosis. 

Antimicrobials regularly useful in:

1. Cholera: 

Tetracyclines (Doxycycline), Cotrimoxazole,

erythromycin.

2. Campylobacter jejuni

Norfloxacin, fluorquinolones. Erythromycin

3. Clostridium difficale associated pseudomembranous colitis: 

Metronidazole.

4. Amoebiasis and giardiasis

Anticholinergic agents:

Can reduce bowel motility and secretion, have poor

effect in secretary diarrhoeas.

Octreotide:

Somatostatin analogue, potent antisecretory and antimotility action on gut. 

These are opioid drugs which:

• Reduce propulsive movements
• Diminish intestinal secretions
• Enhances absorption 

MOA: Mediated via µ receptors (enteric neuronal network)

Codeine:

Anti-diarrhoeal effect attributed to its action on small

intestine and colon. 

Paracetamol (Acetaminophen) Mechanism of Action

Nepal Vs India U16 SAAF Live Result

Nepal U-16 Rishi Magar 20'

1 0 Match in Progress SAFF U-16 Championship 08-Aug-2011 03:30 PM NST Dasrath Stadium

India U-16

	28 '	India's two strikers; Laldanta Sanga and Daniel are looking for counter moves. Biswas, Sanjaya,Bibesk and Sagar Lama - Nepalese defenders are playing well.
	26 '	Nepalese boys are now marking the Indian defenders well, Supporters are behind them.
	25 '	What is this? should have been Red Card! Suman Lama is fouled. Yellow card is given. Free kick to Nepal. Nepal skipper, Heman Gurung steps in to take the shot, wow... going..going..going! MAN! inches above the bar!
	22 '	Nepalese supporters are still dancing! Wow! electrifying environment here. I am still remembering the back heel flick of Suman Lama, just like Cristiano Ronaldo!Huuuuuuuuuuuu! You lovely boy!
	21 '	Dangerous, India on attack! Daniel flicks the ball luckily, it angles away, Total luck to Nepal... Comeon Nepalese colts, you need to mark the striker well!
	20 '	GOAL..GOAL.GOAL!!!!!!! What a GOAL for Nepal.. Credit goes to Suman Lama, what a nimble show, just like Christianon Ronaldo, but it hits the bar and Rishi Thapa Magar is right there to place the ball. GOAL.GOAL!!! Nepal are 1-0 up! GOAL Rishi Thapa Magar
	18 '	Oh hooo., dangerous but luck to Nepal, Sanjaya Rajbahak slides to tackle the ball but it hits the leg of Daniel, Nepalese goalie, Birendra is out from his position but he manages to catch the ball. Phewwwwww!
	17 '	Daniel of India is looking dangerous, Nepalese boys need to makr him properly. Lovely Biswash, what a neat pass to Rishi, Can he score from that position, not more than 20 yard, powerful shot but goes little wide.
	16 '	counter move by Indians, Daniel is well challenged by Sanjaya Rajbahak, what a tackle, lovely! Good job Rajbahak.
	14 '	Rishi Thapa magar is fouled by Raja Rawat, referee gives a foul kick to Nepal. wow, Nepal..Nepal..Aditya Choudhary steps in to kick the ball, he's got power in his legs, shoots powerfully but the ball skies over the ball.
	12 '	Indian coaches are asking their goalie, Supratim to shoot long ball to Nepal D box, I can see Indian coaches instructing their goalie!
	11 '	Sagar Lama fouls on Lalram, referee whistles for a foul, Raja Rawat is ready with the ball, Nepalese goalie, Birendra Chand is shouting at his boys, Rawat curls the ball, well caught by Chand.
	10 '	Indians are playing aerial ball. Off side trap here by Nepalese boys and Laldanta Sanga is caught! this could be dangerous.
	8 '	Shorter Nepalese boys are holding the ball possession, Indians are looking for counter moves from the start. Aww, our senior team coach, Graham Roberts is shouting at the boys! Rishi..Rishi...
	6 '	Biswas shrestha is in the left field, crosses the ball to Suman and Rishi but the ball curls out. Nepalese boys are putting Indians udner pressure.
	5 '	Good pass by Rishi to Suman Hamal, Myron tackles the ball well. Good start by both teams.
	4 '	First corner kick of the match, Nepal earns it, Nepal..Nepal..everywhere, Heman Gurung is ready with the ball, Sajid clears the ball from D-box.
	3 '	India: Supratim (GK), Myron, Suman, Sajid, Nabin, Kamalpreet, Germanpreet, Lalram, Raja, Daniel, Laldanta
	2 '	Nepal : Heman, Aditya, Sanjaya, Anil, Birendra (GK), Umesh, Rishi, Bibek, Biswas, Sagar, Suman
	1 '	Peeeep! here we go. Nepal U-16 vs India U-19/ Watch LIVE video at www.goalnepal.com.np. Mizamizanpur from Bangladesh is the man in charge.
		Wow..Nepal..Nepal already! Nepal are in red shirts while Indians are in blue shirts.
		Both teams are under tunnel, ready for the match. Here echoes the FIFA anthem.
		Pakistan won the match against Bangladesh and are through to final. Nepalese colts are ready to do the same.
		Hello, big match here at Dasrath Stadium. More than 5000 spectators are here supporting Nepal...only Nepal! Stay with us, we are 10 mins away to kick off the match.

Photographs in White House when Laden was killed!!!

Sometime after midnight last night I Tweeted this: "Can't wait to see White House photographer Pete Souza's behind-the-scenes photos of the past few days' events." Souza has delivered. For the past several years, the White House chief photographer has been chronicling every moment of the Obama Administration. He has unprecedented access to the President and his staff and gets himself into meetings and rooms you'd think he wouldn't ever be allowed. Case in point: Souza was in the Situation Room with President Obama, Vice President Biden, Secretary of State Hillary Clinton, and other senior officials while the mission in Pakistan to take out Osama bin Laden was taking place yesterday. The photo above is truly remarkable — check out the no-BS look on the President's face and Secretary Clinton's expression of near shock at what she's watching. Absolutely awesome. We can only guess that they're watching the mission unfold via a camera mounted on one of the Navy SEAL's helmets. Check out more cool photos from yesterday's events in the White House after the jump.

By the way, one more thing about Souza's photos. He posts a selection of them every day on theWhite House Flickr feed, and perhaps even cooler, every single photo that he and his staff takes are protected pieces of the National Archives. Which means that he's not allowed to delete any photos and the entire collection will be made available to the public following the completion of Obama's presidency. That's pretty amazing.