Thursday, 30 July 2015

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TNF alpha n Interleukin -1 are cytiokines produced in RA synovium, try n make abs against the two.

Osteoarthritis--Give cox enzyme as antigen.

Crystal arthropathies--
Gout --already dealt try immune supressing vac.
Calcium pyrophosphate dihydrate arthropathy--try immune supressing vac. Give cox enzyme as antigen.
Spondyloarthritides--Ankylosing spondylitis--TNF alpha is the cytiokines produced try n make abs against it.

Enteropathic spondyloarthropathies--Associated with Crohn's  n Ulcerative colitis--Try immune supressing vac. Give cox enzyme as antigen.
Psoriatic arthritis--Try immune supressing vac. Give cox enzyme as antigen.Give TNF alpha as ag.

Reactive arthritis--Try immune supressing vac. Give cox enzyme as antigen.

Juvenile idiopathic arthritis--Try immune supressing vac. Give cox enzyme as antigen.

Autoimmune connective tissue disease--
Systemic sclerosis--Limited Systemic sclerosis of which CREST syndrome is a part--Calcinosis, Raynauds, Oesophageal n gut dysmotility, sclerodactyly n Telengiectasia.
n Diffuse Systemic sclerosis--Anti topoisomerase-1 n anti RNA polymerase ab found 
Therapy--Try immune supressing vac.

Relapsing polychondritis--Try immune supressing vac.

Polymyositis n Dermatomyosiis-- Try immune supressing vac.

Rheumatoid factor is positive in Sjogren's syndrome, Felty's syndrome, RA, Infection (endocarditis, hepatitis)

Anti nuclear antibody--

Endocrine--Thyroid peroxidase ab--Hashimotos thyroiditis (80-95%) Graves(50-80%)
Islet cell ab, Glutamic acid decarboxylase(GAD)--Type 1 DM. In D.M an autoimmune response develops against GAD bcoz it share 6amino acids with P2C replicative complexes of coxsackie B4 virus.There are a few abs formed against GAD, islet autoantigen 2,insulin abs, islet cell abs. TO trteat DM prepare abs against these abs or inhibits the immune process make abs against CD28 T cells or inhibit IL-2 n 4 or all the cytokines, interferon gamma is specially produced in mouse model tht promotes DM. Prevent the progression of DM.
I always felt that abs were formed against insulin n that is why the insulin resistance, so in a pt with high grade of insulin resistance supress the ab production against insulin as well n the safest n specific way is to make abs against abs, immune supression not very right,already immunosupressed bcoz of high sugar where the microbes cud grow easily, make a vaccine using the abs as antigens.

T/t or prevention of D.M--Make abs against abs n prevent D.M.

Renal-C-anca specificity for serine proteinase-3.
Perinuclear p-anca with specificity for myeloperoxidase.
Microscopic  polyangitis (45%), Churg strauss , Goodpasture's.
ANCA may be positive in UC/Chrohn's , primary sclerosing cholangitis, autoimmune hepatitis,Felty's, RA, SLE or drugs( antithyroid, allopurinol, sulfasalazine, ciprofloxacin)

Neuromuscular --Acetylcholine receptor, ab-Myasthenia gravis.Make abs against abs, supress immunity.

Vasculitios--Supress immunity.
Giant cell arteritis--Supress immunity.
Polymyalgia rheumatica--Supress immunity.
Polyarteritis nodosa--Supress immunity.

Systemic conditions causing eye signs

Granulomatous disorders--Syphilis,TB, Leprosy, Brucellosis n Toxoplasmosis cause inflmn in the eye--Give cox enzyme as antigen, this will control inflammation.

Connective tissue disease--Reiter's, PAN,SLE, Ankylosing spondylitis also give rise to eye problems--Supress immunity.

Keratoconjunctivitis sicca--Sjogren's, SLE,RA , Sarcoidosis--Give cox enzyme as antigen, this will control inflammation.

Skin manifestations--

Skin manifestations--
Erythema nodosum--
Erythema multiforme--
Erythema chronicum migrans--
Erythma marginatum--try immune supressing vac.
Erythma gangrenosum--try immune supressing vac.
Vitiligo--try immune supressing vac.

Listen for all the above skin condn give a cox inhibitor an inflammatory, bcoz this is all a sequelae of inflammation,in all autoimmune condn ag ab interaction will be followed by ag-ab interaction n then complement n WBCs will play a role, only immune supressing vac will also work.

To prevent the development of complns in Dm give aldolase reductase antagonist or vaccine.
Will prevent the conversion to sorbitol (n later later fructose )n dec in myoinositol n that leads to diabetic complns, cataract being one of them make this antagonist fast father developing cataract:).Sorbitol n fructose Will also cause neuropathy n retinopathy.

How to prevent the complications of Diabetes caused by advanced glycosylation end product.

The AGEs have a no of chemical n biologic properties that are potentially pathogenic.

Glucose + protein---->Schiff base----K2 reversible days---Amadori product----KN irreversible(weeks)------>Protein cross link in advanced glycosylation end product.The AGEs have a no of chemical n biologic properties that are potentially pathogenic.

We will prepare abs or antagonists (if u feel antibodies won't work shud then make antagonists) against the AGE receptors n prevent the negative effects.

Properties of AGEs.
Biologic
Bind to AGE receptors on monocytes n mesenchymal cells
Induce--Monocyte emigration
Cytokine n GF secrn
Inc vascular permeability
Procoagulant activity
Enhanced cellular proliferation
Enhanced extra cellular matrix production.

Chemical
Cross link polypeptide of same protein.
Trap monoglycosylated proteins(eg--LDL,Ig,complement)
Confer resistance to proteolytic digestion.
Induce lipid oxidation
Inactivate NO
Bind nucleic acids.

The chemical effects can also be reversed by the use of pharmacologic agents but what not mentioned or read anywhere like CO :)binds with RBCs use a chemical that binds with --NH2 n prevents the binding of glucose to proteins this is for non enzymatic glycosylation for enzymatic glycosylation use the glycosylation enzyme antagonist or abs.

T/t of ANEURYSM-- Find out obstruction in the blood vsls of the brain by angiography i.e pass a radio opaque dye n image n then pass a cannula thru the vertebral arteries n then pass a normal bored needle with a sclerosant that passes out of the blood vessel n place the sclerosant in the perivascular space n then let the aneurysm fibrose n thus danger of a future haemorrhage cud be avoided.If circulation ahead wanted n there is no collateral supply then pass a stent n inject a sclerosant around the aneurysm so that the aneurysm gets fixed to it, see whether will work.This was for T/t of berry's aneurysm in the brain 2 dangerous, cud be treated thus.This cud be used to treat aneurysms in the body as well.Similarly if there is an obstruction as happens in the heart in coronary artery disease then one cud pass stents to prevent ischaemia n brain stroke, one cud use gamma rays to remove the atheroma which is made up of smooth muscle hypertrophy n some calcified plaques.


-->Either visualise calcium stones thru radiations or else use a radio opaque Contrast will help visualise a simple growth in the body or gut or obstruction in the lumen of the vessel wall. Calcium salt solutions cud also be used as a radio opaque medium bcoz Xrays don't pass thru bones,Ok:).Blood carries the contract medium to every nook n corner thru the arteries n then cappilaries to the cells n tissues n back thru the veins, so if we give any chemical or drug thru one of the blood vessel will reach every cell this cud be used to send surfactants  one cud pass it into the lung thru the airways but this route will always work,same with genes n enzymes. In condn where there are fewer myocytes as in an elderly heart or in brown atrophy one cud incraese the no of myocardial cells by giving growth factors n cytokines as used in hepatic regeneration shud work...


Familial defective apoprotein B-100, make abs give the rt apoprotein
T/t of Tangier's disease---There is hyoalphalipoproteinemia there is low HDL,Give alphalipoproteins will inc HDL.

Primary LDL abnormalities--Hypobetalipoproteinemia associated with increased longevity, so give abs against betalipoproteins.

T/t of porphyrias --Haematin given, already mentioned defn enzymes given will also work.

Eponymous syndrome n their t/t

In Barret oesophagus photodynamic therapy involves light induced activation of an orally administered photosensitizer such as 5-ALA which causes the acculumulation of protoporphyrin 9 in GI mucosal cells?? Not being able to digest, what we will do is treat jaundice by phototherapy, similarly find out all the chemicals in the body that are photosensitive at different wavelengths n we can use light as a chemical/drug/enzyme.

Behcet's dis--Give immune supressant vaccine.

Berger's disease--Give immune supressant vaccine.

Bickerstaff's brainstem encephalitis--Give immune supressant vaccine, check.

Budd chiari syndrome--If bcoz of thrombosis of hepatic vein then give vac against thrombus.

Buerger's disease (thromboangitis obliterans)--Give immune supressant vaccine.

Caplan's syndrome--Give vaccine against COX.

Chrug Strauss syndrome--Give immune supressant vaccine.

Creutzfeldt jacob disease--Give immune supressant vaccine.

Crigler Najjar syndrome--Give UDP-glucuronyltransferase enz.

Curtiz fitz hugh syndrome-Give bacterial vaccines.

Devic's syndrome(Neuromyelitis optica)--Give immune supressant vaccine.

Dressler's syndrome--Give immune supressants and/or anti inflammtory agents for a short while, myocardial necrosis causes abs formation against heart muscle, pt experiences fever,chest pain, pleural n pericardial rub.

Dubin johnson syndrome--Make abs against transporter protein n give correct transporters from outside.

Dupuytren's contracture--Low grade Xanthine oxidase abs.

Fabry's disease--  Alpha galactosidase is given.

Fanconi anaemia--Give rt stem cells.

Felty's syndrome--Give immune supressant vaccine.

Foster kennedy syndrome--Treat the hydatid, plasmacytoma, meningioma--gama ray ablation.

Freidrich's ataxia--fraxetin gene mRNA antagonist or make a vaccine against that mRNA.

Froin's syndrome--Treat the tumor in spinal cord--gama ray ablation.

Gardner's syndrome-- APC gene mRNA antagonist or make a vaccine against that mRNA.

Galineu's syndrome(narcolepsy)--Give immune supressant vaccine that stops abs formation against hypocretin containing neurons.

Gilbert's syndrome- Give UDP-glucuronosyltransferase transferase.

Gilles de la taurette syndrome--Give immune supressant during strpt infection, there is a defect in devpt of basal ganglia as well.

Henoch schonlein purpura--Give immune supressant vaccine to prevent vasculitis.

Huntington's chorea--Gene mRNA antagonist or make a vaccine against that mRNA.

Jervell Lange Nielsen syndrome--give the rt gene n mRNA abs of the defective K channel subunit.

Kaposi's sarcoma--Give cytokines, TNF alpha.

Klippel trenaunay syndrome- Gene's mRNA antagonist or make a vaccine against that mRNA.

Langerhan's cell histiocytosis--Give immune supressant vaccine.

Leriche's syndrome--Use gamma rays n burn the saddle embolus at the bifurcation of aorta.

Short duration fast is good for diabetes bcoz will break the glucose protein bond n prevent organ n cell damage bcoz the earlier bond is reversible.

Loeffler's eosnophilic carditis--Give immune supressant vaccine.

Loeffler's syndrome-Give immune supressant vaccine.

Marchiafava bigami syndrome--Like Wernicke's.

Marchiafava michaeli syndrome--Give stem cells.

Marfan's syndrome--Fibrilin 1 gene mutation, Gene's mRNA antagonist or make a vaccine against that mRNA n give the rt gene like the enzyme if doesn't work try vectors.

Menetrier's disease--Cause not known, give bact vac.


Mikulics syndrome--Give immune supressant vaccine.

Nelson's syndrome--Make abs against ACTH.

Make abs against MSH cud decrease melanin.

Ogilvie's syndrome-- Make low titre abs against acetylcholine esterase.

Ortner's cardiovocal syndrome--Due to pressure on recurrent laryngial nerve due to enlarged l.atrium or aortic dissection ,can do nothing

Osler weber rendu syndrome (Hereditary haemorrhagic telengiectasia)--Gamma or laser ablation.

Pancoast's syndrome--Due to pressure on recurrent laryngial nerve can do nothing

Perinaud's syndrome--Due to pressure on nerves can do nothing other than removing the cause.

Peutz jegher's syndrome--Gene LKB1 mRNA antagonist or make a vaccine against that mRNA n give the rt gene like the enzyme if doesn't work try vectors

Peyronie's disease-use gamma rays to remove fibrosis, can be helpful in removing excess fibrosis i.e collagen tissue deposition from contractures burn or keloid..

Pott's syndrome--Anti TB.           

Prinzmetal angina--Try low titre vaccine against ca channels.

Raynaud's syndrome--There is spasm of blood vessel here now:) Sympathetic system is responsible for vessel dialatation so if we go for sympathectomy will not cause dialatation book says sympathectomy wonder how, we can try making low titre vaccine against Ca channels.

Refsum's syndrome--Accumulation of phytanic acid bcoz of mutation of the gene coding for peroxisomal enz phytanoyl-CoA-hydroxylase.Give Gene's mRNA antagonist or make a vaccine against that mRNA n give the rt gene like the enzyme if doesn't work try vectors or else give enzymes.

Romano ward syndrome-A mutation in K+ channel, Make gene's mRNA antagonist or make a vaccine against that mRNA n give the rt gene like the enzyme if doesn't work try vectors. Brugada syndrome--Faulty sodium channel predisposes to arrythmias.. Make gene's mRNA antagonist or make a vaccine against that mRNA n give the rt gene like the enzyme if doesn't work try vectors.

Rotor syndrome--First go thru Dubin Johnson syndrome then will understand Rotor's
In Dubin Johnson there is coinjugated  hyperbilirubinaemia, go thru on ur own Harrison medicine I will just give conclusion on my own.There is defective expression of MRP2 an ATP dependant canalicular membrane transporter, several mutations in MRP2 gene produce Dubin Johnson phenotype which has autosomal recessive inheritance. Bcoz of defective transport the bilirubin regurgitates into the circulation by passing into the blood stream instaed of moving towards gall bladder.
There are two naturally occuring  coproporphyrin in urine 1 n 3 normally more than 75 % is 3, I isomer is raised in urine in Dubin johnson, will try to tell when haeme is synthesised from Glycine n Succinyl CoA it passes thru different stages see the pathway of porphyrin synthesis, this takes place in the cytoplasm n last 2 steps in the mitochondria, Haeme synthesis takes place in the liver Ok:) most probably the carrier that carries Coproporphyrin 3 is a bit defective while the carrier carrying coproporphyrin 1 is more active N so this difference.

A cardinal feature is accumulation in lysosomes of centrilobular hepatocytes of dark, coarsely granular pigment.as a result the liver may be  grossly black in appearance.This pigment is thought to be derived from epinephrine metabolites that are not excreted normally. what have to say is liver is the site where all the chemicals of the body are metabolised n excretory products made bcoz of carrier defect the metabolites get accumulated n produce a dark pigment.What is the color of VMA?

Biliary excretion of  a no of anionic compounds is compromised. Bromosulphalein BSP is used in LFT. The rate of  dissapearance of BSP after i.v bolus administration is observed. BSP is conjugated with glutathione in the hepatocyte n the resulting conjugate is normally excreted rapidly in canaliculus. Here there is a reflux after 90 mins after injection due to reflux into circulation from hepatocyte.
This again is bcoz of a carrier defect

So to treat we will GIVE gene's mRNA antagonist or make a vaccine against that mRNA n give the rt gene that will make the transporter if doesn't work try vectors.

In rotor's syndrome an autosomal recessive disorder clinically similar to Dubin Johnson syndrome. There is rise in conjugated bilirubin , here there is no inc pigmentation of liver, The gall bladder is visualised n not is Dubin.., which means the dye carrier is absent here, Coproporphyrin 1 is less than 70%,, BSP clearance delayed but no reflux. there are various carrier defects correct them n u have a cure, was interesting going thru the details of the defect.
Try n see whether transporters cud be given thru blood will not work. The carriers determine whether to carry the product to the hepatic duct system or blood vessel, if there is an obstruction in the duct system regurgitates into the blood not after entering the gall bladder as had thought in school. Bcoz VMA n urea etc  they enter the blood not the duct each product has its own destination.

Sister Mary Joseph nodule--Gamma ray ablation of the umbilical nodule caused by metastatic deposit from an intra abdominal malignancy.

Sjogren's syndrome--Give immune supressant vaccine.

Steven johnson syndrome-Give immune supressant vaccine.

Sturge weber syndrome--t/t Laser or gamma ray ablation of haemangioma in the brain (as well as face portwine stain for this laser has been in use), will do wonders bcoz the tt used is hemisperectomy for intractable seizures. Had been thinking of why children were injected steroids in paediatric surgey for similar condns n yesterday was going thru piles n also thinking about varicose veins bcoz a dear aunty had mentioned that she had that problem, and whaterever I come across stays solid in the mind.
Use gama ray or laser ablation of varicose veins n piles after visualising by MRI, Wow:).

Varicose veins are dialated tortuous veins caused due to weakness of the vessel wall or absence of a valve, while dialated plexus of superior haemorrhoidal veins in relation to anal canal is haemorrhoids or piles.
T/t 4 varicose veins is use of crepebandage, sclerosant, trndelnberg's surgery where the three tributaries of Saphenous veins are cut n ligated n the vein itself is cut n ligated at the point where it joins the femoral vein, we cannot cut this vein thru these rays bcoz blood will collect bcoz we will not be able to ligate the blood vessels if we are able to ligate by burning just at the distal end then the work will get easier but chances of success I feel is low otherwise cud be a wonderful treatment to stop a bleeding vessel in brain haemorrhage.

Tt of piles--
Lord's dialatation:),the int sphincter is widely stretched which is supposed to releive the venous congestion n improve piles, indicated in grade 1 varices,it is supposed to rupture pecten bands can try n rupture them with the above radns
Injection of sclerosant which causes aseptic thrombosis, injn is given perivascular, use gamma rays to burn the pile mass.
Barron's band application--Bands applied at the neck of the haemorrhoids causes necrosis n the pile gets fibrosed.
Haemorrhoidectomy-- Excision of the pile mass
Cryosurgery--Liquid nitrogen at -196 DEG c is applied to pile mass which coagulates the tissues.

There cud be bleeding from the distal end the vein, the the perforators will get avulsed from long Saphenous vein n get thrombosed after the long Saphenous vein is removed as happens in Trendelenberg's surgery n gamma ray ablation, if the same happens at the distal end of the Long Saphenous vein n varicose veins well n good but if not then we will have to take some measures, one can use sclerosant at the distal end see if cryotherapy with liquid nitrogen at -196 deg C causes sufficient coagulation n stops bleeding, for piles go thru the anal canal n use sclerosant at the distal end then need not burn the rest of the tissues only sclerosant is sufficient:). but difficult in the removal of long Saphenous bcoz of the long course.



Anatomy of the Long saphenous vein.
The L.saphenous vein is A continuation of the dorsal venous arch runs superficial n passes from infront of the medial malleolus to the medial aspect of the upper end of the thigh where joins the Femoral vein
Has three tributaries at the termination-- Superficial circumflex iliac,Superficial epigastric n Superficial external pudendal.
Tributaries in the leg--
Anterior vein of the leg
Posterior arch vein which connects the med perforators to the L.saphenous vein, is a constant vein.
Tributaries in the lower thigh
4 in no they connect the long Saphenous with  s.saphenous vein are called communicators.

Perforators--Connect L.saphenous vein with the deep system of veins, since they perforate deep fascia called perforators.
Leg perforator--They are 3 in no.
Knee perforator-- 1 in no, below knee.
Thigh perforator--1 in no. above knee.
Physiology--The bld flows from L.saphenous vein to deep system of veins, they are present in the calf muscle soleus muscle hence called soleal plexyus of veins.When the calf muscles contract the blood will not enter into the the superficial system of veins bcoz of one way valves present in the perforators,when these valves absent or weak , perforator incompetence develops resulting in varicose veinsw got it, get it:).


So to summarize the tt of varicose veins --ligate the distal ends or else use a sclerosant, burn out the long Saphenous vein thru radns, this is just like Trendelenbrg's surgery where after ligation of the distal end the vein is pulled out how, pass a metallic stripper n bring it out at the upper end , a metallic head is attached to the stripper n the vein is avulsed I thought this on my own n later thought wud be too painful but later found had read this yrs back n now the bleak memory came back (earlier thought wud be too brutal n now realised am too sensitive comments go on dont pay heed) here the benefits are no use of knife. Compln cud be oedema of the leg or exaggeration of the varicosity in the early post op period when only the sclerosant used for the closure of the distal end.


Takayasu's arteritis--Give immune supressant vaccine. Give methotrexate in severe resistant conditions.

Tietze syndrome(Idiopathic costochondritis)--Give vac againt cox in low titre if no response give immune supressant vaccine.

Todd'palsy-24 hrs palsy recovers on its own.

Von hippel lindau syndrome--There is a mutation in one of the genes the tumor supressor gene is mutated so tt is make gene's mRNA antagonist or make a vaccine against that mRNA if at all some abnormal product being formed bcoz of the mutation n give the rt gene i.e tumor supressor gene either thru blood or a vector. Here there is a germ line mutation of a  tumor supressor gene on chromosome 3p , which predisposes to bilateral renal cell carcinoma, retinal n retinal haemangioblastoma n phaeochromocytoma, may present with visual impairment or cerebellar signs. SO Syndromes are bcoz of a mutation that affects many systems, or bcoz of immune hyperactivity conclusion till now in majority of the cases.

A new discovery a mutation that leads to formation of an oncogene which will be responsible for a sporadic case of cancer if this is carried in the germline then it becomes familial now a Vaccine for all known cancers, all cancers are bcoz of a mutation some are familial some are sporadic, what we will do is study the genetic make up of the person n find out about all the abnormal mutations present in the genotype n give vaccines against the mRNA fron the mutant gene, this can be used for all diseases caused by abnormal mutations as mentioned above:).This can be tried for sporadic cancers as well specially those who are at risk or cud be given prophylactically, which means there is a particular mutation in all the known cancers so give an mRNA vaccine against all of them, but this also means that new mutations cud come up n newer variety of cancers cud also come up n then new vaccines will have to be tried.

Just as virus's Nucleic acid after crossing the cell membrane reaches the nucleus similarly if DNA enters the cells will act like a virus n we will not need a vector but the point is how will the Dna cross the cell membrane, bases that are the end result of nucleic acid digestion will be absorbed from the GIT n enter the circulation n then enter the different cells n in dividing cells where needed will be used up for new DNA synthesis. So in that case the Dna can also enter the cell, howz this:).

So in a fetus with a major genetic condition where the mother has a precious baby we cud try mRNA antagonist n give the rt gene to the mother or use a non pathogenic viral vector  every time the cell replicates in a fetus will multiply like a plasmid or integrated at an abnormal site bcoz of integrase of the virus,give it in the blood n see as well, but this cud correct the deposition of abnormal structural proteins after three mnths when the immune system with the haematopoetic system develops, the vaccine will have to be given thru the cord, but the point is that the regulatory mechanism for the expression of that gene may or maynot work, if it doesn't work the vaccine will be a flop:(.

We will also have to give T stem cells with CD-28, thru the cord will augment immunity, this cud also be given when antiviral enzyme vaccine is given in utero, will augment immunity n similarly cud be given to the mother as well. In this case bcoz mother has not been given CD28 stem cells the mother will not produce abs against the mRNA.
Anywhere where a vaccine or abs have to formed against the body's normal tissues give T stem cells with CD28.

How is it that a sporadic cancer becomes a familial cancer?
If the mutation or entry of a viral oncogene takes place in the germ cells then will be carried to the next generation n generation after generation :) n will lead to breast ca, stomach ca etc.Same is the case with syndromes if mutations take place in the germ cells will be carried from one generation to the next if tolerable. If the mutation takes place in any cell of the body other than the germ cells then will be a spordic case of a ca or syndrome.

Antigen processing n stages of immune response.
An antigen is processed in the body b4 lymphocytes can interact with it. Macrophages do this function and link between non specific n specific immune response .Macrophages phagocytose microbes or non cellular antigens non specific response .Phagocytosed material is broken down into fragments capable of  reaction  with receptors on the surface of lymphocytes.

First step is recognition by the lymphocytes-- Lymphocytes recognise the specific antigen which it encounters .Antigen gets bound to specific receptors on the surface of lymphocyte this binding is called recognising. Differentiation of one antigen from other is determined by nature of receptors lymphocyte have.

Lymphocyte activation--Lymphocyte that has combined with antigen undergoes cycle of mitotic divisions.This process is termed as lymphocyte  activation.This process is termed as lymphocyte activation .This process usually occurs at the site of recognition i.e mostly in peripheral lymphoid tissue.

Attack--Activated cells attack against the antigens of the kind that has initiated the immune response.Nature of attack varies with the type of lymphocyte .May be antibody mediated or cell mediated.B lymphocyte are responsible for humoral attack while NKcells are responsible for cell mediated response.

Antibodies are proteins present in plasma membrane of B lymphocyte. These B cells differentiated into plasma cells which secrete abs

Antibodies combine with antigen and then direct an attack that eliminates antigen or cell bearing the antigens. Elimination is done either by phagocytosis or complement.

So various ags are released when there is an infection n abs are formed against various fragments not specifically a single protein n they go for further inhibition, destruction of the ag takes place when present on the surface where complement or phagocytes reach, will not enter the cell.

If a single enzyme antigen does not work against virus then use enzyme antigens seperately for each virus n see whether they work.

Whipple disease--Caused by Tropheryma whippeli, give antibiotics.

Zellweger syndrome-- A rare autosomal recessive disorder,  causative gene is PEX1 , the syndrome is severe form of infantaile Refsum's syndrome n exhibits similar biochemical abnormalities. T/t make gene's mRNA antagonist or make a vaccine against that mRNA if at all some abnormal product being formed bcoz of the mutation n give the rt gene or else give the rt deficient enzyme like in Refsum's syndrome.

Zollinger ellison syndrome-- Associated with peptic ulcers with gastrin  secreting adenoma gastrinoma, the adenoma is usually found in the pancreas but may be found in  the stomach n duodenum. Most cases are sporadic some associated with MEN type 1, 60% are malignant.
Treat like a cancer make a vaccine against the mutant DNA's mRNA or protein product of the mRNA cud be a gf or gf receptor etc.


















Tribute to Dr APJ Abdul Kalam

Ek tara chamka tha is kahkasha,
jalkar bujh gaya woh chiraga,
aaj ankhen hain purnam dil hai ghamzada,
jisne khilaya tha ek gulistaa,
aaj peeche chod gubbar kar gaya use veeran,
aaj nahi raha woh hamara pyara mehman,
bataya har kadam zindagi hai ek imtehan,
jisne himmat bandhaya chulo aasman,
sarparast tha jo har kadam tha ek saya,
aaj woh nahi dekh aanken hain hairan,
usi ke saaye hum banen hai hamara armaan,
khushiyan phailayi bana duniya ko ashiyan,
sadiyon se chalta ja raha duniya ka karvan,
ek accha insaan bano to banegi dastaan,
na ho duniya ke chakachaund se tum pareshan,
tai karo tum har doori har faaslaa,
karte chalo tum dilon ke ranjishen bejaa,
sab ko sath le badho nasibon se milta kafila,
chod chalo apne peeche apna namo nishaan,
yaad karega sada tumhe ye sara jahan hamara,
wohi to tha santari wohi  paasban hamara.

Thursday, 23 July 2015

sc



Inherited kidney disease--
Polycystic kidney disease--Remove cyst by puncturing with gamma rays or laser instead of going for laproscopic surgery.
Primary hyperoxaluria--Due to an enzyme defect,give correct enzyme from outside.
T/t of Diabetic nephropathy--Glucose control n keep the Bp less than 125/75. ACE inhibitor n A2A even if normotensive this decreases the intraglomerular pressure.
Osteoclast stimulation when new bone formation
Osteoclast inhibition when osteoporosis, give anabolic steroids.
Treat multiple myeloma like malignancy n give vaccines to supress IL4 n other interleukins that act as growth factors, bcoz steroids also given.
Make the cancer vaccine by using antigens on the cell surface of cancer cells if formed n see whether will work.
vaccine t/t for cancer
PROTEIN PRDTS OF ONCOGENES
Growth factors--Oncogene such as ras cause overexpression of growth factors genes n thus gfs.
Abnormal Growth factor receptors--The oncogenic version of the receptors are associated with persistent dimerization and activation without binding to the growth factor.Hence the mutant receptors deliver continuous mitotic signal. So what we will do is use this receptor as an antigen n make a vaccine.
Growth factor receptors are activated by mutations, gene rearrangements n overexpression,The ret proto oncogene a receptor tyrosine kinase exemplifies oncogenic conversion via mutations n gene rearrangements....go thru Robbins
Overexpression of grwoth receptors-- There is over expression of normal grwoth receptors.
---Now to treat cancer we will antagonize the growth factor, the growth factor receptor that is abnormal or the growth factor receptor that is in excess n like anti metabolite is going to affect the entire body, to create a vaccine we can use all the three as antigens but will not be specific so what we will do is use the mutant grwoth receptors as ag howz this? gr8, too much torture pain , palpitaion, the books did not open on compu, dirty talk to disturb n this is God's work.
Signal transducing proteins--In the inactive state ras protein binds guanosine diphosphate, when the cell is stimulated by gf or other receptor ligand activation ras becomes activated by exchanging GDP for GTP, The activated ras in turn excites MAP kinase pathway, MAP kinases so activated target nuclear transcription factors n thus promote mitogenesis.
GTPase activity hydrolyse GTP to GDP thereby returning ras to its ground state.
So we will target the GTP n MAP kinase i.e make abs against MAP kinase n thus inhibit transcription, GTP will be hydrolysed to GDP by GTPase so instead of abs give this enzyme or GTPase activating protein(GAP) these bind to ras n activate its GTPase activity by more than a 1000 fold, abs will be too non specific. GAPs are like tumor brakes but the irony is that is not able to augment GTPase activity in a mutated ras.
No probs ahead if u continue reading ahead Path Robbins says that franesyl transferase inhibits ras so we can use this as an antigen or else make antagonists if abs not formed.
We can make abs against the oncogene its mRna or protein n antagonize the growth of cancer.
Anti aging vaccine:)--Apoptosis gene P53 when activated releases a protein product that causes apoptosis if we make abs against that factor then we can prevent aging but will cause a lot of cancers bcoz the damaged dna which cud become cancersi.e only half mutated when apoptosis takes place does not produce cancers so give the vaccine for cancer first n then give anti apoptosis vaccine will prevent cell death, but the damaged cells will die.
Nuclear transcription proteins--Tortured so that left studies.
Anti sense oligonucleotide this can antagonise all abnormal genes in cancers n genetic diseases, we can use them to treat CANCERS by giving them from outside, but will be better to use a oncogene or oncoprotein as an antigen n make antibodies against all cancers A whole host of oncoproteins including prodts of myc, mnb, jun n fos oncogenes have been localized to the nucleus, abs formed enter the nucleus as happens in SLE, of these myc gene is most commonly involved in human tumors.
Make a vaccine with myc-max as antigen this is a transcription activator
Similarly give myc-max to allow cell multiplication n prevent apoptosis n cell aging.
Use ornithine decarboxylase as antigen this is necessary for DNA synthesis.
Cyclin N Cyclin dependant kinases--When a cell receives growth promoting signals the synthesis of D type cyclins that bind (cyclin dependant kinases) CDk4 n CDK6 is stimulated in the early part of G1. Later in the G1 phase of cell cycle the synthesis of E cyclin is stimulted which in turn binds to CDK2. The Cyclin D/CDK4, CDK6 N cyclin E/CDK2 complexes phosphorylate the retinoblastoma protein, this unshackles the E2F proteins n they in turn activates the transcription of several genes whose prdts are essential for progression thru the Sphase. These include DNA polynerases, thymidine kinase, dihydrofolate reductase n many others The targets phosphorylated by A/CDK2, B/CDK1 are not fully known, B/CDK1 complex phosphorylatesa variety of proteins required for mitosis..
Natural Antagonists of CDKS--p21,p27,p57 inhibit the CDKs broadly.p15,p16,p18,p19 are sometimes called INK4 proteins bcoz they inhibit CDK4 n CDK6.
Cyclin dependant kinases drive the cell cycle by phosphorylating critical target proteins we can use them as vaccines to prevent cancer growth.
This cancer study began with Multiple myeloma.
Burkitt's lymphoma is a B cell tumor n Multiple myeloma is a plasma cell tumor to treat this tumor we can make vaccines,in hybridoma tech we will use B cell tumor.
T/t
antigf, here growth factors are ILs, esp 2,4,5 n 6, they are growth factors for T n B cells.
antigf receptors-normal n abnormal (this is more specific)
anti MAP kinase
anti franesyl transferase
antisense oligonucleotide
anti oncogene oncoprotein
anti myc max
anti ornithine decarboxylase
anti cyclin n Cyclin dependant kinases.

sc

Causes of haemolytic anemia
Acquired

Immune mediated
--Drug induced
               (--Causing formation of RBCs autoantibodies from binding to the RBC membrane eg--penicillin or production of immune complexes eg--quinine.
This means the RBC membrane rendered antigenic bcoz of a foreign chemical)

Autoimmune haemolytic anaemia--Warm AHA n cOLD AHA--
Causes--of Warm AHA--lymphoprtoliferative condns like CLL, Lymphoma, drugs ,autoimmune diseases like SLE. Cold AHA may follow EBV infn n Mycoplasma  pneumoniae infn --Give ILs or IL4 as antigen or make the abs antigenic n produce abs ie vaccine.

Paroxysmal Cold haemglobinuria--Give IL or IL4 as antigen or make the abs antigenic n produce abs ie vaccine.

Isoimmune-Give IL or IL4 as antigen or make the abs antigenic n produce abs ie vaccine.

Microangiopathic haemolytic anemia--(Causes are HUS, TTP, DIC, Pre eclampsia n Eclampsia, Prosthetic valves---Give the anti thrombus vaccine for all.

Infection-- eg-- Malaria, haemolysis n Black water fever (haemoglobinuria).

Paroxysmal nocturnal haemoglobinuria--Inherited loss of surface glucophasphatidylinositol (GPI)

Hereditary

G6PD deficiency--Give the defn enz, give glutathione n other oxidants.

Pyruvate kinase defn--Give the defn enz.

Membrane defect--
Hereditary spherocytosis--Defn of spectrin structural protein, can do nothing.
Hereditary eliptocytosis

Haemoglobinopathy--Sickle cell anaemia, Thallasemia.

T/t--PNH onwards give right stem cells will not be able to replace the defective cells but will be a source of correct blood cells.

Bleeding disorder--

1.vascular defects (congenital)
Osler weber rendu syndrome--
Ehler danlos syndrome--
pseudoxanthoma elasticum--

Gene therapy in the zygote will be of help

2.Thrombocytopenia--
Decreased marrow production-- Aplastic anaemia, megaloblastic anaemia, marrow infilteration, marrow suppression,
GIive stem cells
Excess dextruction--
Immune--Immune thrombocytopenic purpura.ITP is caused by abs formed against platelets leading to phagocytic destruction. other autoimmune conditions like  SLE, CLL,drugs eg--heparin n viruses. Give IL or IL4 as antigen or make the abs antigenic n produce abs ie vaccine.
Non immune--TTP, HUS, sequestration (in hyperspleenism )--Give antithrombus vaccine.
Decreased platelet function

3.Coagulation disorder
Congenital--Haemophilia, Von Villebrand 's disease-Give missing factor
Acquired--Anticoagulants, liver disease , DIC, vit k defn--T/t accordingly.


T/t of obesity esp post menopausal.
Was thinking about obesity, MI natherosclerosis in post menopausal phase n its cure so opened this lesson cellular pathology in Robbins, t/t is the same give  antiobesity vaccine but bcoz one cannot control the dose of ag where there is a cross reactivity we will control the immune process by controlling the amount  of B7-1 Tlymphocytes n to decrease the immune process use IL antagonists or abs. Oestrogen is protective, after menopause the fat increases in the body.
All major classers of lipids can accumulate in cells, triglycerides cholesterol n cholesterol esters, phospholipids, fatty acids etc n abnormal complexes of  carbohydrates n lipids accumulate in lysosomal storage disease.
 What I wanted to know was that why was it that different people had different body shapes n what was the cure, cure is the vaccine n probably the presence  of various lipid receptors in various cells that allow the fatty acids to enter led to different body shapes this is controlled genetically, details find  out.Go thru the effects of estrogen on fat metabolism have to type lots not being able to gain access to books on the compu since yesterday a way to slow n  stop me so will slowly type out things in brief.

T/t for Liver failure n cirrhosis

Hyperplasia refers to inc in the no of cells of the body.
Of two types-- hormonal n compensatory
Hormonal--Female breast at puberty n pregnancy.
Compensatory--Partial hepatectomy.

Partial hepatectomy---Priming------Release of gf n cytokines like HGF, TGF-alpha, EGF,TNF-alpha, IL-6 Others n Adjuvants like NE, Insulin n glucagon,thyroid  hormone cause proliferation--------Growth inhibitors like TGF beta n other GF n adjuvant dec cause Growth inhibition.

uSING the above knowledge we will give the above growth factors to patients with Liver failure n cirrhosis n this will help in liver cell proliferation.

How to help the brain cells grow?

We can use the above growth factors for growth of the most imp area of the body the brain cells, normally there are certain cells in the body that do not  divide like the myocardial fibres they only hypertrophy this is bcoz OF transforming growth factor beta TGF beta, but even the heart cells multiply in a  malignancy.

What happens in a malignancy? Go thru protein product of oncogenes
There is  inc in GF--We will inc the gf similarly here
Inc in GF receptors normal n abnormal--The receptors cannot be modified.
Signal transducing proteins--We can give MAP kinases.
Nuclear transcription proteins--myC is the oncogene which is a transcription activator, we can do nothing here.
Cyclins n Cyclin dependant kinases--They are cell cycle regulators, We can give B/CDK1 D/CDK4,CDK6,E/CDK2... complexes this is finally going to activate  various enzymes that will cause the cells to multiply the details in breif.

--When a cell receives growth promoting signals the synthesis of D type cyclins that bind (cyclin dependant kinases) CDk4 n CDK6 is stimulated in the early  part of G1. Later in the G1 phase of cell cycle the synthesis of E cyclin is stimulted which in turn binds to  CDK2. The Cyclin D/CDK4, CDK6 N cyclin E/CDK2  complexes phosphorylate the retinoblastoma protein, this unshackles the E2F proteins n they in turn activates the transcription of several genes whose prdts  are essential for progression thru the Sphase. These include DNA polynerases, thymidine kinase, dihydrofolate reductase n many others The targets  phosphorylated by A/CDK2, B/CDK1 are not fully known, B/CDK1 complex phosphorylatesa variety of proteins required for mitosis..

Thus by using some growth n multiplication factors we can cause the body cells that have stopped dividing to go into division but in a controlled manner,  this cud prove to be very useful in old patients where the body has aged the brain functioning gone down n all the systems not working to their proper  extentor a patient who has suffered a stroke both brain n heart...

How to prevent aging?

Werner's syndrome is a condition where there is premature aging, if we grow cells in a culture medium the cells from these patients have a markedly reduced  in vitro life span, after a fixed number of divisions all cells become arrested in a terminally non dividing state known as cellular senescence.

Telomeres are short repeated sequence of DNA (TAAGGG) that compose the linear ends of chromosomes n are imp in
1.Ensuring the complete replication of chromosome ends n
2. Protecting chromosome termini from fusion n degradation.
The sequences are formed by a specialized ribonucleoprotein telomerase an enz that stabilizes telomere length by adding to the ends of chromosomes.
The activity of telomerase is repressed by regulatory proteins which restrict telomere elongation thus providing a length sensing mechanism.Telomerase  activity is expressed in germ cells n is present in low levels in stem cells but is usually absent in somatic cells n tissues.

--What we will do is give telomerase in a controlled amount that will prevent the shortening of telomeres n prevent cell senescence n final multiplication  arrest but take care bcoz telomerase activation cud make a cell cancerous.

T/t for Werner's syndrome, Cockyne syndrome n Ataxia telengietasia.
In Werner's syndrome the defective gene product is DNA helicase involved in DNA replication n repair n unwinding, a defect in this enz leads to accumulation  of chromosomal damage a that mimics the injury that accumulates during  normal cellular aging. Give this enzyme shud work.
Cockyne syndrome n Ataxia telengietasia cud be similarly corrected. In ataxia there is a defect in the DNA repair mechanism the mutant ATM gene has sequence  similarity to phosphatidyl inositol3 kinases that are involved in signal transduction, give the correct gene product that repairs the DNA will be a cure.


How to delay heart surgery in valvular heart disease?
 In the myocardial fibres there is only hypertrophy this is bcoz of  transforming growth factor beta TGF beta.
In the heart there are at least two group of signals,
Mechanical triggers such as stretch n
Trophic triggers such as polypeptide growth factors n vasoactive agents (angiotensin 2 , alpha adrenergic agonists)

The heart hypertrophies bcoz of the above two factors to decrease the stretch take diuretics n 2
Decrease the trophic triggers give ACE inhibitors or angiotensin receptor antagonists....Use the knowledge above n one can prevent hypertrophy n early  surgery..


Tuesday, 21 July 2015

SC

Vac t/t for hirsuitism n virilism--Make a vaccine with testosterone as antigen i.e altered testosterone structure, almost all the basic organic compds life is made of such as carbohydrates, proteins, fat n nucleic acid act as antigens.
Pcos is one condn where oestrogen when given decreases the level of testosterone by inc serum sex hormone binding globulin therefore decrease in free androgens.One proof that antibodies formed against bodies own chemicals (here hormones.)
In liver cirrhosis the level of oestrogen goes up this again is an example that shows that if we inhibit the metabolism of a drug the level of a hormone or chemical goes up.
In hepatic encephalopathy the urea that enters the brain is converted by astrocytes to glutamine by glutamate, excess glutamine is responsible for an osmotic imbalance followed by cerebral oedema bcoz is responsible for drawing in fluid into the cerebral tissues. What we can do is give glutamate dehydrogenase antagonists in a patient with hepatic encephalopathy developing cerebral oedema bcoz this rkn takes place in the presence of glutamate dehydrogenase.
To lower Bp we produce obstructions on the way like take a garden pipe carrying water to lower the pressure of the water being carried we will apply constricting bands which will decrease the pressure of fluid ahead, cerebral haemorrhage is the most dreaded compln of hypertension so we will go for throat temponade:) a constricting band on the neck will decrease the pressure a bit, howz it?
T/t of chronic granulomatous condition.
One decrease inflammation.
Two augment immunity to end the chr inflmn.
If bcoz of autoimmune process give abs against abs n give lipoxygenase antagonists.
Vac that will lower Bp in a chronic hypertensive pt--Autoimmune hepatitis is one condition where anti smooth muscle antibodies(SMA) are formed in 80%, using this what we can try is use these abs to destroy the smooth muscles lining the intima of the blood vessel n thus lower the pressure in a blood vessel where the smooth muscle hypertrophy has narrowed the lumen we can go for passive immunisation or else go for active immunisation with a short dose antigenic exposure which will accordingly produce abs for a short duration in low titres. What happens in atherosclerosis is that macrophages consume excess modified lipoproteins forming foam foam cells, which when accumulate leads to release of growth factors that stimulte the proliferation of smooth muscle and causes calcification of plaque.
Similarly anti liver or kidney microsomal type 1 abs are formed in this condition, these are sites for lipogenesis i.e fatty acid chain elongation, so by creating abs against the microsomal system its functioning can be inhibited...
Vaccine against autoimmune condns (esp cell mediated )like that for organ rejection--Use Cyclophilin or Calcineurin present in the Tcells as antigen n prepare antibodies now the abs formed will bind with the above n inhibit the subsequent reactions required for the syntheSis of number of a no of cytokines including IL-2. IL-2 is the main stimulus for the increase in the number of T lymphocytes. So in a viral infn n cancer give IL-2 will augment CMI.
This is the mechanism of action of cyclosporine n Tacrolimus used for the treatment of Ulcerative colitis, which means that this is an autoimmune condition responsible for relapsing n remitting inflammation of the colonic mucosa. Can be used for autoinmmune hepatitis, primary biliary cirrhosis...etc.
So for the treatment of chronic inflammatory or granulomatous conditions what we can try is augment immunity n see whether the chronic condition ends if doesn't then try giving the above vaccine or anti inflammatory vaccine, inflammation always harms so gud to give the anti inflammatory vaccine. Sulfasalazine a folate antagonist is effective in inflammtory bowel disease bcoz the gut bacteria convert this drug into sulfapyridine n 5-aminosalicylate, latter exerts anti inflammatory action.
Crohn's disease-Similar chronic transmural granulomatous condition, give vaccines against cyclophilin n phospholipase.
Irritable bowel disease--Short dose vaccine against seratonin or receptors.
Carcinoid tumor--This makes me feel that something is about to happen, this is a tumore that produces many hormones like insulin, glucagon,ACTH,parathyroid n thyroid, bradykinin, tachykinin, subst p, VIP, gastrin n the treatment is so wonderful octreotide already been discovered a somatostatin analogue, this made me think that this is a tumor of neural crest origin n that forms the pituitary n various chemical mediators n hormone in the body, so what we can do is that instead of giving a person insulinoma n carcinoid tumor to replace pituitary failure n lack of insulin will be better if we give pituitary n beta cells after maturing them from stem cells will be a perfect cure in any of the endocrine gland failure just as the carcinoid is regulated by octreotide can be regulated from a distant site as well like difficult to place the pituitary in the sella turcica in the cranial cavity so place it at an easily accessible site.Will work.
T/t of Endocrine failure-- 1hypothalamus, 2pituitary, 3thyroid,4 parathyroid, 5pancreas--alpha, beta, delta cells,6adrenals, 7ovaries n 8testes.Replace 1,2,3,4,5,6,7,8 all the cells from the various tissues secreting hormones cud be placed in differant areas when there is endocrine failure, howz this:).
Leydig cells produce testosterone even in a fetus under the effect of HCG which acts as LH mainly FSH n TSH activity as well(responsible for development of the male ext genitalia)Leydig cells cud be transplanted in testicular failure n see whether it worked. Theca cells in the female are responsible for the synthesis of oestrogen n progesterone so can be used in menopausal females.
Pituitary has cells of three histological types--
Chromobhobe--70%--Secrete PRL,ACTH,GH.
Acidophil--15%--GH.PRL
Basophil--7%--ACTH.
pITUITARY has been classified according to the hormone secreted as well, so take the cell according to the hormone being secreted which is done by immunohistology n then replace those cells in the body so that rt amount of hormones released.
Same cud be tried for the other endocrine glands.
Coeliac disease--This is a T cell mediated autoimmune disease of the small intestine in which prolamin (alcohol soluble protein in wheat, barley, rye+/-oats) intolerance causes villous atrophy n malabsorption, which means this is an autoimmune condition where cross reactivity with prolamin leads to ab mediated destruction of villi, so t/t will be Gluten free diet no prolamins n during acute phase treat like an autoimmune condn.
This made me think about the lesions produced in leprosy n felt was almost similar which meant ag-ab rkn was playing a role n read about the two forms of the disease Tuberculoid n lepromatous.
In tuberculoid leprosy form similar to those seen in TB containing epitheloid macrophages , giant cells and a few surviving mycobacteria paucibacillary type.In brief I will say that T helper n supressor n cytotoxic all cells come into the picture n there is release of IL2 which provokes CMI n IL4 which provakes humoral immunity which induces ab formation by the B cells .The lepra bacilli has affinity for the nerve tissue n skin n they grow in them n the immune process while destroying them harm the nerves, skin , muscle etc n so the observed pathology (Search not working:( so cud not copy n paste the pathogenesis from Robbin plz go thru on ur own).
T/t--So what we will do is we will supress immunity by giving vaccine against IL-2 n IL-4 or cyclophilin n ab against ab or whatever discussed earlier:) N Anti inflammation vaccine against phospholipase so that chr inflammation stops n then give bacterial enzyme vaccine like bacterial enzyme vaccine or bacterial dna polymerase vaccine, this is the principle of rifampicin check keep forgetting:)given in TB n leprosy n hopefully this will work.
SUMMARY
The Nephrotic Syndrome
The nephrotic syndrome is characterized by proteinuria, which results in hypoalbuminemia and edema. Podocyte injury is an underlying mechanism of proteinuria, and may be the result of nonimmune causes (as in MCD and FSGS) or immune mechanisms (as in MN).Minimal change disease (MCD) is the most frequent cause of nephrotic syndrome in children; it is manifested by proteinuria and effacement of glomerular foot processes without antibody deposits; the pathogenesis is unknown; the disease responds well to steroid therapy.Focal and segmental glomerulosclerosis (FSGS) may be primary (podocyte injury by unknown mechanisms) or secondary (e.g. as a consequence of prior glomerulonephritis, hypertension or infection such as HIV); glomeruli show focal obliteration of capillary lumens, hyaline deposits and loss of foot processes; the disease is often resistant to therapy and may progress to end stage renal disease.Membranous nephropathy (MN) is caused by an autoimmune response against an unknown renal antigen; it is characterized by granular subepithelial deposits of antibodies with GBM thickening and loss of foot processes but little or no inflammation; the disease is often resistant to steroid therapy.
SUMMARY
The Nephritic Syndrome
The nephritic syndrome is characterized by hematuria, oliguria with azotemia, proteinuria, and hypertension.The most common causes are immunologically mediated glomerular injury; lesions are characterized by proliferative changes and leukocyte infiltration.Acute post-infectious glomerulonephritis typically occurs after streptococcal infection in children and young adults but may occur following infection with many other organisms; it is caused by deposition of immune complexes mainly in the subepithelial spaces, with abundant neutrophils and proliferation of glomerular cells. Most affected children recover; the prognosis is worse in adults.IgA nephropathy, characterized by mesangial deposits of IgA-containing immune complexes, is the most common cause of the nephritic syndrome worldwide; it is also a common cause of recurrent hematuria; it commonly affects children and young adults and has a variable course.Hereditary nephritis is caused by mutations in genes encoding GBM collagen; it manifests as hematuria and slowly progressing poteinuria and declining renal function; glomeruli appear normal until late in the disease course

Glomerular Diseases
Primary Glomerular Diseases
Minimal-change disease
Focal and segmental glomerulosclerosis
Membranous nephropathy
Acute postinfectious GN
Membranoproliferative GN
IgA nephropathy
Chronic GN
Glomerulopathies Secondary to Systemic Diseases
Lupus nephritis (systemic lupus erythematosus)
Diabetic nephropathy
Amyloidosis
GN secondary to lymphoplasmacytic disorders
Goodpasture syndrome
Microscopic polyangiitis
Wegener's granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis-related GN
GN secondary to extrarenal infection
Thrombotic microangiopathy
Hereditary Disorders
Alport syndrome
Fabry disease
Podocyte/slit-diaphragm protein mutations

Pathogenesis of Glomerular Diseases
Although we know little about the etiologic agents or triggering events, it is clear that immune mechanisms underlie most types of primary glomerular diseases and many of the secondary glomerular diseases. Experimentally, GN can be readily induced by antibodies, and glomerular deposits of immunoglobulins, often with various components of complement, are found frequently in patients with glomerulonephritis. Cell-mediated immune mechanisms may also play a role in certain glomerular diseases.
Crescentic Glomerulonephritis
Type I (Anti-GBM Antibody)
Idiopathic
Goodpasture syndrome

Type II (Immune Complex)
Idiopathic
Postinfectious/infection related
Systemic lupus erythematosus
Henoch-Schönlein purpura/IgA nephropathy

Type III (Pauci-Immune) ANCA Associated
Idiopathic
Wegener granulomatosis
Microscopic angiitis
Interstitial Nephritidis
Acute tubulointerstitial nephritisin breif is mediated by immune response to drugs, infns n other causes.

Tubulointerstitial nephritis (TIN) refers to a group of inflammatory diseases of the kidneys that primarily involve the interstitium and tubules. The glomeruli may be spared altogether or affected only late in the course. In most cases of TIN caused by bacterial infection, the renal pelvis is prominently involved-hence the more descriptive term pyelonephritis (from pyelo, "pelvis").
The term interstitial nephritis is generally reserved for cases of TIN that are nonbacterial in origin. These include tubular injury resulting from drugs, metabolic disorders such as hypokalemia, physical injury such as irradiation, viral infections, and immune reactions. On the basis of clinical features and the character of the inflammatory exudate, TIN, regardless of the etiologic agent, can be divided into acute and chronic categories....
SUMMARY
Tubulointerstitial Nephritis
Inflammatory diseases primarily involving the renal tubules and interstitum. Acute pyelonephritis is a bacterial infection caused either by ascending infection as a result of reflux, obstruction, or other abnormality of the urinary tract, or by hematogenous spread of bacteria; characterized by abscess formation in the kidneys, sometimes with papillary necrosis.Chronic pyelonephritis is usually associated with urinary obstruction or reflux; results in scarring of the involved kidney, and gradual renal insufficiency.
Drug-induced interstitial nephritis is an IgE- and T cell-mediated immune reaction to a drug; characterized by interstitial inflammation, often with abundant eosinophils, and edema.Analgesic nephropathy is the result of consumption of large amounts of certain analgesics; may result in papillary necrosis and progressive renal dysfunction.
Autoimmune process involved in the latter grp will deal with mangt of this grp.
Amyloidosis--causing proteinuria, nephrotic syndrome n progressive renal failure.
T/t So what we will do is where ever ag ab rkn involved we will supress immunity by giving vaccine against IL-2 n IL-4 or cyclophilin n ab against ab.
Any condition where immune supression wanted steroids,cyclosporin, tacrolimus,infliximab given, one can give this vaccine.
HUS-haemolytic uraemic syndrome is a condn where endothelium injury causes intravascular thrombosis, this leads to ARF n thrombocytopenia.
TTP-Thrombotic throbocytopenic pupura--Deficiency of a protease that normally cleaves multimers of von villebrand factor, large multimers formed causing platelet aggregation n fibrin deposition in small vessels leading to microthrombi.
T/t- we can give the antithrombosis vaccine in the above two conditions.
Sequelae of what have borne these 14 yrs that killed me everyday n has more than half killed me--
Just as one can perform surgery thru gamma rays on the coronary blood vessels similarly one can correct the renal artery narrowing bcoz of atherosclerosis n that can correct hptn to a great extent.

sc

With the use of enzyme vaccine we can make vaccines against streptococcus as well, so can vaccines be made for all mutable forms virus n bacteria.Mutations in diff bacteria n virus produce different strains this is not only observed in virus but bacteria as well which means mutations take place that fast in human beings as well, decrease the use of carcinogens/mutagens.
 Influenza vac also can be made similar to AIDS that is vaccine against RNA polymerase enzyme.

What happens in DIC? This is a condition which is caused by

Tissue injury
Obs compln
Malignant neoplasm
Massive trauma
bURNS
surgery

Sepsis
Gm -ve
Other infns

Endothelial injury
Aortic anerysm
Haemolytic uremic syndrome
severe burns
Acute glomerulonephritis



Tissue injury n Sepsis-------->Tissue thromboplastin------>Extrinsic coagulation pathway------->Intravascular coagulation.
Endothelial injury------------>Platelet aggregation------->Intrinsic coagulation pathway------>Intravascular coagulation.
Intravascular coagulation-------Consumption of clotting factors n platelets----------->Bleeding.
Intravascular coagulation------>Plasmin activation------------>FDP---------->Inhibit platelet aggregation,thrombin n fibrin polymerisation---------->Bleeding
Intravascular coagulation----------->Microvascular occlusion------------>Ischaemic tissue injury n microangiopathic haemolytic anaemia.

t/t--When there is fear of DIC give intrinsic n extrinnsic factor antibodies or antagonists prophylactically towards term, one can similarly create a vaccine by giving any one of those factors as antigen, during a massive bleeding provide the missing factor from outside but the pic will be similar to haemophilia cud be dangerous during delivery so give passive immunisation or give antagonists . If this vaccine is given to the mother the fetus will become haemophiliac if the child suffers from autoimmune conitions.This made me think about fetal vaccines had been thinking since some time. During pregnancy give enzyme vaccine against viral infections will protect the fetus after 3mnts when the abs start forming but will damage the fetus in the first three months so give the vaccine as early as possible bcoz the mother's abs will protect.

If we give the mother any vaccine will act as a vaccine for the fetus as well after three months.

Vaccine to prevent teratogenic intrauterine infections.
vIRAL
AIDS,
Hepatitis B,
Rubella,
Cytomegalovirus,
HSV-2,
Varicella zoster virus.
NON VIRAL
Toxoplasma,
Treponema pallidum
Bacteria appears to be non teratogenic still we can protect the fetus against them thru vaccines n drugs.Give killed, recombinant or enzyme vaccine.
wE can vaccinate the mother before pregnancy which is the norm with TORCH vaccine  or else whenever she  wishes to after she is pregnant,earlier viral vaccines were not given during pregnancy bcoz the fetus just like any ambryo is a very good medium for the growth of virus n it is considered that the live attenuated vaccine is one where the pathogenicity is quite suppressed but not totally supressed so when the immune cond is poor can become pathogenic, so what we will do is give a recombinant vaccine where the pathogenicity gene has been totally removed or else give an enzyme vaccine. The recombinant or the enzyme vaccine will improve the immunity i.e form abs n protect the fetus after 3 mnths when the immune system develops..this will act as a vaccine not only for the mother but also for the fetus, the mother's ab will also protect the fetus we can also give drugs to the mother which will protect the fetus.


For the t/t of Chronic granulomatous condition give T cell stem cells with b7-1 this can also be given for AIDS n malignancies.

Granulomatous Inflammation--A Short list.

 Tuberculosis Mycobacterium---tuberculosis---Noncaseating tubercle (granuloma prototype): a focus of epithelioid cells, rimmed by fibroblasts, lymphocytes, histiocytes, occasional giant cells

 Leprosy Mycobacterium---leprae Acid-fast bacilli in macrophages---noncaseating granulomas

 Syphilis Treponema---pallidum Gumma---microscopic to grossly visible lesion, enclosing wall of histiocytes; plasma cell infiltrate; central cells are necrotic without loss of cellular outline

 Cat-scratch disease---Gram-negative bacillus---Rounded or stellate granuloma containing central granular debris and recognizable neutrophils; giant cells uncommon

 Sarcoidosis---Unknown etiology---Noncaseating granulomas with abundant activated macrophages

Crohn disease (inflammatory bowel disease)---Immune reaction against intestinal bacterial, self-antigens Occasional noncaseating granulomas in wall of intestine, with dense chronic inflammatory infiltrate.

Principal Granulomatous Conds
Bacterial
Tuberculosis
Leprosy
Syphilis
Granuloma inguinale
Brucellosis
Cat scratch dis
Tularaemia
Glanders

Fungal
Actinomycosis
Blastomycosis
Cryptococcosis
Coccidiodomycosis

Parasitic
Schistosomisiasis

Misc
Sarcoidosis
Crohn's disease
Silicosis
Berylliosis
Foreign body granulomas

Vac against interstitial lung disease--
Give Phospholipase as ag n make a vaccine, a lot of autoimmune condns responsible for the above condn so need not give a lot of Tcell augmentation.
Today's conclusion-- Augment immunity if it works well n good if it doesn't then inhibit it by giving autoimmune condn vaccine n vaccine against inflammation.
Extrinsic allergic alveolitis--
Give IgE as ag or give abs against IgE.