Zanmbeel: February 2008

Monday, February 18, 2008

LOBACT Laema Chemi Pharma

LOBACT Laema Chemi Pharma
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Forte Susp: Per 5ml: Trimethoprim 80mg, sulphamethoxazole 400mg. Paed Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Forte Susp(002321):50ml: 17.00:20.00.
Paed Susp(002322):50ml: 11.33:13.33

LOBACT Laema Chemi Pharma

KAYTRAN Karachi Chemical

KAYTRAN Karachi Chemical
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: DS Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg.Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
DS Tabs(010999):20x5's: :-.
Susp(010550):50ml: 11.51:13.54.
Tabs(010998) :20x10's:-:-.
Tabs(010998):200's:-:-.

KAYTRAN Karachi Chemical

INFECTRAN Zafa

INFECTRAN Zafa
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs(005117) :20x10's: 140.25:165.00.
Tabs(005117) :200's: 140.25:165.00

INFECTRAN Zafa

DECTRON Delux Chemical

DECTRON Delux Chemical
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Susp(033678):60ml: 9.35:11.00

DECTRON Delux Chemical

Tuesday, February 12, 2008

FLOCOT Flow Pharma,EFTRAN Efroze

EFTRAN Efroze
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.DS Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs(010856) :200'S: 174.23:204.98.
DS Tabs(013550): 100's: 189.44:222.87

FLOCOT Flow Pharma
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs(021834) :200's: 208.25:245.00.

FLOCOT Flow Pharma,EFTRAN Efroze

OUTRAN DS Pharmix

OUTRAN DS Pharmix
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs(017542):20x5'S: 219.84:258.64

OUTRAN DS Pharmix

Co-Trimoxazole

Co-Trimoxazole
Mnfgs.Mktg. in Generic:Pack:TP:RP:
Batala Pharma(026298):20x10's: 185.30:218.00.
Batala Pharma (026298) :200's: 140.25:165.00.
Batala Pharma (026299) :(DS Tabs):20x5's:185.30:218.00.
Batala Pharma (026299) :(DS Tabs):100's:178.50:210.00.
Jawa:(011598):200's:237.15:279.00;Tabs.
Jawa: (011598): 10x20's: 237.15:279.00;Tabs.
Jawa:(011599):100's: 236.56:278.30;DS Tabs.
Jawa:(011599):5x20's: 237.15:279.00; DS Tabs.
Jawa:(011600) :50ml: 12.25:14.41 ;Susp.
Jawa:(011600):400ml: 68.00:80.00;Susp.
UniPharma:(019621) :50ml: 10.00:12.00;Syp.
UniPharma:(019621):120ml: 16.00:18.00;Syp.
UniPharma:(019621):450ml:44.00:46.00;Syp.
UniPharma:(019620):200's(Jar):210.00:245.00;Tabs.
UniPharma: (019620) :200's(Box):218.00:256.00;Tabs

Co-Trimoxazole

CO-TRIMAX Ideal

CO-TRIMAX Ideal
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg.Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Susp(010852):400ml: 39.00:72.00.
Susp(010852):50ml: 7.00:14.00.
Tabs(008550):20x10's: 80.00:257.00.
Tabs(008550) :200's: 76.00:231.00.
Tabs(008550):200's: 78.00:23100

COTRIGEN Genera Pharma

COTRIGEN Genera Pharma
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg.
Regn.No:Pack:Trade Prices: Retail Prices:
Susp(021542):50ml: 11.47:13.50
Tabs(021543):20x10's: 215.73:253.80.
Tabs(021543): 100's: 133.11:156.60

CO-TRIMAX Ideal

COTRIGEN Genera Pharma

COTRI Unexolabs

COTRI Unexolabs
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: DD Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs (004429) :200's: 237.00:279.00.
DD Tabs (06438); 100's: 215.00:253.00.

COTRI Unexolabs

COMAX Marvi

COMAX Marvi
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg.Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Susp(008927):50ml: 10.94:12.87.
Susp(008927):400ml: 54.45:64.06.
Tabs(008928) :20x10's: 203.87:239.85

COLITRAN pdh

COLITRAN pdh
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: DS Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg.Tabs: Trimethoprim 80mg, sulphamethoxazole400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
DS Tabs(008541):20x5'S: 212.50:250.00.
Susp(005540):50ml: 12.58:14.80.
Tabs(005541) :20x10's: 212.50:250.00

COMAX Marvi

COLITRAN pdh

COBACT English Pharma

COBACT English Pharma
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Susp(014207):50ml: 12.88:15.16

COBACT English Pharma

BOSCHTRIM Bosch

BOSCHTRIM Bosch
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: DS Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
DS Tabs(015929):25x8's: 280.50:330.00.
Tabs(015928) :20x10's: 153.00:180.00

BOSCHTRIM Bosch

BIPRIM Ankaz

BIPRIM Ankaz
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Forte Susp: Per 5ml: Trimethoprim 80mg, sulphamethoxazole 400mg. DS Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.
Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg,
Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
DS Tabs(008409):10x10's: 253.94:298.75.
Forte Susp(007542):50ml: 17.52:20.61.
Susp (007541 ):50ml: 12.16:14.30.
Susp (007541 ):400ml: 49.48:58.21.
Tabs(008077) :20x10'S: 253.94:298.75

BIOTRAN Geofman

BIOTRAN Geofman
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: Forte Susp: Per 5ml: Trimethoprim 80mg, sulphamethoxazole 400mg. Forte Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.
Susp: Per 5ml: Trimethoprim 40mg, sulphamethoxazole 200mg,
Tabs: Trimethoprim 80mg, sulphamethoxazole 400mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Forte Tabs(005414):20x5's: 215.43:253.45.
Forte Susp(022083):50ml: 11.85:13.95.
Susp (006567):50ml: 11.85:13.95.
Tabs(004409) :20x10's: 233.48:274.68.

BIPRIM Ankaz

BIOTRAN Geofman

BACTY-FORTE Flow Pharma

BACTY-FORTE Flow Pharma
Drug Category: Folic acid inhibitor/sulphonamide.
Generic Name: Co-trimoxazole.
Contents: DS Tabs: Trimethoprim 160mg, sulphamethoxazole 800mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs(022925): 100's: 187.00:220.00

BACTY-FORTE Flow Pharma

Saturday, February 9, 2008

NICOSUR Zafa

NICOSUR Zafa
Drug Category: Vitamin.
Generic Name: Nicotinic acid.
Contents: Tabs 250mg/500mg: Nicotinic acid.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 250mg(011956):100's: 51.51:60.60.
Tabs 500mg(011957); 100's: 89.25:105.00.

NICOSUR Zafa

SORBIC Paramount Pharma

SORBIC Paramount Pharma
Drug Category: Vitamin.
Generic Name: Ascorbic acid.
Contents: Tabs: Vit. C 500 mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 500mg(000893): 47.66:56.07.

SORBIC Paramount Pharma

SORBIC Paramount Pharma
Drug Category: Vitamin.
Generic Name: Ascorbic acid.
Contents: Tabs: Vit. C 500 mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 500mg(000893): 47.66:56.07.

Friday, February 8, 2008

ROROCIN Polyfine

ROROCIN Polyfine
Drug Category: Macrolide
Generic Name: Roxithromycin
Contents: Tabs 150mg: Roxithromycin 150mg
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 150mg(028755 ):10's 140.25 165.00

ROMYCIN Surge Labs

ROMYCIN Surge Labs
Drug Category: Macrolide
Generic Name: Azithromycin
Contents: Caps 250mg: Azithromycin (as dihydrate) 250mg
Susp: Per 5 ml Azithromycin (as dihydrate) 200mg, powder for suspension to be prepared as per instruction on the pack
Regn.No:Pack:Trade Prices:Retail Prices:
Caps 250mg(024331):1x6's 140.25:165 00
Susp 200mg (024332) 15ml: 140.25 165.00

ROROCIN Polyfine

ROROCIN Polyfine
Drug Category: Macrolide
Generic Name: Roxithromycin
Contents: Tabs 150mg: Roxithromycin 150mg
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 150mg(028755 ):10's 140.25 165.00

ROMYCIN Surge Labs

RIDINFECT Medicraft

RIDINFECT Medicraft
Drug Category: Macrolides
Generic Name: Roxithromycin
Contents: Tabs 150mg/300mg: Roxithromycin
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 150mg(027818) 10's 136.00:160.00
Tabs 300mg(027248):5's: 212.50 250 00

RICKYCIN Flow Pharma

RICKYCIN Flow Pharma
Drug Category: Macrolides
Generic Name: Roxithromycin
Contents: Tabs 150mg: Roxithromycin 150mg
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 150mg (029717) 10's: 107 10 126.00

RIDINFECT Medicraft

RICKYCIN Flow Pharma

RICKYCIN Flow Pharma
Drug Category: Macrolides
Generic Name: Roxithromycin
Contents: Tabs 150mg: Roxithromycin 150mg
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 150mg (029717) 10's: 107 10 126.00

R1BOXIN Searle

R1BOXIN Searle
Drug Category: Macrolides
Generic Name: Roxithromycin
Contents: Tabs 150mg: Roxithromycin 150mg
Indications: Roxithromycin sensitive infections of ENT, bronchopulmonary, genital (excluding gonococcal infections) and skin. Prophylaxis of meningococcal meningitis in subjects who have come in contact with the patient
Dosage: Adults: 150mg in the morning and evening before meals Children: 6-11 kg: 25mg in the morning & evening; 12-23kg: 50mg in the morning & evening; 24-40kg: 100mg in the morning & evening.
Contra-ind., Precautions etc: See notes of Erythromycin at the begining of this section
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 150mg(019856):10's: 185.15:217.82

REZOXIN Reko

REZOXIN Reko
Drug Category: Macrolide
Generic Name: Azithromycin
Contents: Caps 250mg: Azithromycin (as dihydrate) 250mg
Regn.No:Pack:Trade Prices:Retail Prices:
Caps 250mg(027187):6's 102.00:120.00

R1BOXIN Searle

REZOXIN Reko

REZOXIN Reko
Drug Category: Macrolide
Generic Name: Azithromycin
Contents: Caps 250mg: Azithromycin (as dihydrate) 250mg
Regn.No:Pack:Trade Prices:Retail Prices:
Caps 250mg(027187):6's 102.00:120.00

RESQUE Standpharm

RESQUE Standpharm
Drug Category: Macrolide
Generic Name: Azithromycin
Contents: Caps 250mg: Azithromycin (as dihydrate) 250mg Susp: Per 5 ml Azithromycin (as dihydrate) 200mg, powder for suspension to be prepared as per instruction on (he pack
Regn.No:Pack:Trade Prices:Retail Prices:
Caps 250mg(020956)6's: 147 90:174.00
Susp 200mg (020957) 15ml: 148.75:175.00

RESQUE Standpharm

RESCOMYCIN Rasco Pharma

RESCOMYCIN Rasco Pharma
Drug Category: Macrolides
Generic Name: Roxithromycin
Contents: Tabs 100mg/150mg/300mg: Roxithromycin 100mg/150mg/300mg
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 100mg(038959) 10's: 107.10:126.00
Tabs 150mg(038969):10's: 127.50:150.00
Tabs 300mg(038960):5's: 127.50:150.00

RESCOMYCIN Rasco Pharma

RASTHRO Rasco Pharma

RASTHRO Rasco Pharma
Drug Category: Macrolide
Generic Name: Azithromycin
Contents: Tabs 250mg: Azithromycin (as dihydrate) 250mg
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 250mg(040180) 10 s 216 75:255.00

RANKER Wilshire

RANKER Wilshire
Drug Category: Macrolide.
Generic Name: Clarithromycin.
Contents: Susp: Per 5ml: Clarithromycin 125mg;after reconstitution as per instruction mentioned on the pack tabs 250mg/500mg: Clanthromycin
Regn.No:Pack:Trade Prices:Retail Prices:
Susp(032345);60ml: 255.00:300.00
Tabs 250mg (032956): 10's 204 00-240 00
Tabs 500mg(032957):10-s: 378.25:445.00

RASTHRO Rasco Pharma

RANKER Wilshire

RAKACID Raka Poshi

RAKACID Raka Poshi
Drug Category: Macrolide.
Generic Name: Clarithromycin.
Contents: Dry Susp/Drops: Per 5ml: Clarithromycin 125mg; after reconstitution as per instruction mentioned on the pack.
Tabs 250mg/500mg: Clarithromycin 250mg /500mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Drops(032307):25ml: 76.50:90.00.
Dry Susp(032308) :60ml: 153.00:180.00.
Tabs 250mg(032309):10's: 170.00:200.00.
Tabs 500mg(032310):10's: 197.50:350.00

RAKACID Raka Poshi

PULSATE Sami

PULSATE Sami
Drug Category: Macrolides.
Generic Name: Roxithromycin.
Contents: Dispersible Tabs 100mg: Roxithromycin 100mg. Tabs 150mg/300mg: Roxithromycin.
Regn.No:Pack:Trade Prices:Retail Prices:
Dispersible Tabs (016861 ):10's: 110.50:130.00.
Tabs 150mg(015616):10's: 153.00:180.00.
Tabs 300mg(016660):10's: 272.00:320.00.

PULSATE Sami

PLAZO Platinum

PLAZO Platinum
Drug Category: Macrolide.
Generic Name: Azithromycin.
Contents: Tabs 250mg: Azithromycin (as dihydrate) 250mg.Susp: Per 5 ml: Azithromycin (as dihydrate) 200mg; powder for suspension to be repared as per instruction on the pack.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 250mg(025508):6's: 170.00:200.00.
Susp 200mg(025509):15ml: 140.25:165.00.

PLAZO Platinum

PISCEAN Raka Poshi

PISCEAN Raka Poshi
Drug Category: Macrolide.
Generic Name: Roxithromycin.
Contents: Tabs 150mg: Roxithromycin 150mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 150mg(026720):10's: 142.80:168.00.

PEDIAZOLE Abbott

PEDIAZOLE Abbott
Drug Category: Macrolide/sulphonamide.
Contents: Susp: Per 5ml: Erythromycin ethylsuccinate equivalent to erythromycin 200mg, sulfisoxazole acetyl equiv to sulfisoxazole 600mg.
Indications: Acute otitis media in children.
Dosage: Otitis media: Children: Less than 8kg, 50mg/kg/day (erythromycin component); 8-16kg, 2.5ml; 16-24kg, 5ml; 24-45kg, 7.5ml; over 45kg, 10ml. All four times daily for 10 days.
Regn.No:Pack:Trade Prices:Retail Prices:
Susp(009699) :60ml: 47.52:55.90

PISCEAN Raka Poshi

PISCEAN Raka Poshi
Drug Category: Macrolide.
Generic Name: Roxithromycin.
Contents: Tabs 150mg: Roxithromycin 150mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 150mg(026720):10's: 142.80:168.00.

PEDIAZOLE Abbott

PATHOCIN Wilson's

PATHOCIN Wilson's
Drug Category: Macrolide.
Generic Name: Clarithromycin.
Contents: Susp: Per 5ml: Clarithromycin 125mg;after reconstitution as per instruction mentioned on the pack.Tabs 250mg/500mg: Clarithromycin 250mg/500mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Susp(016729) :60ml: 106.25:125.00.
Tabs 250mg(016724):10's: 131.75:155.00.
Tabs 500mg(024614):10's: 263.50:310.00.

PATHOCIN Wilson's

OXIROM PharmEvo

OXIROM PharmEvo
Drug Category: Macrolides.
Generic Name: Roxithromycin.
Contents: Tabs 100mg/150mg/300mg: Roxithromycin 100mg/150mg/300mg.
Indications: Roxithromycin sensitive infections of ENT, bronchopulmonary, genital (excluding gonococcal infections) and skin. Prophylaxis of meningococcal meningitis in subjects who have come in contact with the patient.
Dosage: Adults: 150mg in the morning and evening before meals. Children: 6-11kg: 25mg in the morning & evening; 12-23kg: 50mg in the morning & evening; 24-40kg: 100mg in the morning & evening.
Contra-ind., Precautions etc: See notes of Erythromycin at the begining of this section.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 100mg(026039):10's: 93.50:110.00.
Tabs 150mg(024719):10's: 59.50:70.00.
Tabs 300mg(024720):5's: 51.00,:60.00

OXIROM PharmEvo

OMICIN S.J.&G. Fazul Ellahie
Drug Category: Lincosamide.
Generic Name: Lincomycin.
Contents: Caps 500mg: Lincomycin (as HCI)500mg.Inj 300mg(1ml)/600mg(2ml): Per ml: Lincomycin (as HCI) 300mg; 1ml(300mg) vial; 2ml(600mg) amp & vial.Syp: Per 5ml: Lincomycin (as HCI) 250mg.
Indications: Serious lincomycin sensitive infections.
Dosage: Caps/Syp: Adults: 500mg three or four times daily. Children: 10-12 years, 500mg four times daily.
Inj: Adults: 600mg by IM in] 12-24 hourly or IV infusion. 8-12 hourly. Children: Under 1 month, not recommended; others, 10mg/kg by IM Inj 12-24 hourly; alternatively 10-20mg/kg daily by IV infusion in 2 or 3 divided doses at 8-12 hour intervals.
Contra-ind: Clindamycin sensitivity.
precautions: Renal, hepatic, endocrine or metabolic disorders. Check liver function and blood regularly with prolonged use.
Interactions: Neuromuscular blocking drugs.
Adverse effects: Persistent diarrhoea, colitis; discontinue immediately.
Regn.No:Pack:Trade Prices:Retail Prices:
Caps(012421):12's: 90.40:106.35.
lnj(012422):1ml: 15.73:18.50.
lnj(012422):2ml: 26.33:31.00.
Syp(021707):60ml: 42.58:50.09.

OLINC Bosch

OLINC Bosch
Drug Category: Lincosamide.
Generic Name: Lincomycin.
Contents: Caps 500mg: Lincomycin (as HCI)500mg.Inj 300mg/600mg: Per ml: Lincomycin (as HCI)300mg, 2ml(600mg) & 1ml(300mg) Inj.
Regn.No:Pack:Trade Prices:Retail Prices:
Caps(025418): 12's: 71.40:84.00.
Inj 600mg(025416):2ml: 21.25:25.00.
Inj 300mg(027158):1ml: 12.75:15.00

OD-3 Adamjee

OD-3 Adamjee
Drug Category: Macrolide.
Generic Name: Azithromycin.
Contents: Caps 250mg: Azithromycin (as dihydrate) 250mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Caps(027648) :2x3'S: 140.25:165.00

OLINC Bosch

OD-3 Adamjee

OD-3 Adamjee
Drug Category: Macrolide.
Generic Name: Azithromycin.
Contents: Caps 250mg: Azithromycin (as dihydrate) 250mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Caps(027648) :2x3'S: 140.25:165.00

NOVICLAR Platinum

NOVICLAR Platinum
Drug Category: Macrolide.
Generic Name: Clarithromycin.
Contents: Susp: Per 5ml: Clarithromycin 125mg; after reconstitution as per instruction mentioned on the pack. Tabs 250mg/500mg: Clarithromycin 250mg/500mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Susp(033725):60ml: 189.55:223.00.
Tabs 250mg(033726):10's: 165.75:195.00.
Tabs 500mg(033727):10's: 316.20:372.00

NOVICLAR Platinum

NOVIBAXIN Novins

NOVIBAXIN Novins
Drug Category: Macrolide.
Generic Name: Clarithromycin.
Contents: Tabs 250mg/500mg: Clarithromycin 250mg/ 500mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Tabs 250mg(033519):10's: 204.00:240.00.
Tabs 500mg(033520):10's: 378.25:445.00

NOVIBAXIN Novins

NOVELINK Platinum

NOVELINK Platinum
Drug Category: Lincosamide.
Generic Name: Lincomycin.
Contents: Caps 500mg: Lincomycin (as HCI).
Regn.No:Pack:Trade Prices:Retail Prices:
Caps(026169):2x6's: 70.80:83.30.

NOVELINK Platinum

NOVELINK Platinum
Drug Category: Lincosamide.
Generic Name: Lincomycin.
Contents: Caps 500mg: Lincomycin (as HCI).
Regn.No:Pack:Trade Prices:Retail Prices:
Caps(026169):2x6's: 70.80:83.30.

Sunday, February 3, 2008

Polymerase chain reaction

INTRODUCTION — The two most important principles underlying the polymerase chain reaction (PCR) are: Complementarity-driven binding of DNA to form a duplex Template-driven, semi-conservative synthesis of new DNA by DNA polymerases
These two principles are discussed separately in detail. (See "Overview of molecular biology").
To complete the theoretical background to understand PCR, a discussion relating to the requirements that specify a unique sequence in the genome, and a review of thermostable DNA polymerases are required. These features as well as a discussion of some research applications of PCR are presented here. An introduction to the clinical applications of PCR can be found elsewhere within UpToDate. (See "Cytogenetic and molecular genetic diagnostic tools").
UNIQUE GENOMIC SEQUENCES — Relatively short DNA sequences suffice to specify a unique sequence in the genome. As an example, assume (although it is not strictly true) that all four bases (adenine [A], thymine [T], guanine [G], and cytosine [C]) are equally frequent in the approximately 3 X 10(9) residues of the human genome. It is possible to calculate the expected frequency of a sequence of N bases having a specified sequence using simple probability theory; that frequency is given by the following formula:
(3 X 10(9))[1/4(N)]
The expression 1/4(N) expresses the chance that the sequence of an N-residue oligonucleotide matches a given sequence. The constant 3 X 10(9) is simply the size of the human genome in bases. The following are examples of this calculation for four different oligonucleotide lengths: A specific oligonucleotide that is 10 nucleotides long occurs approximately 3000 times in the human genome. An oligonucleotide that is 15 nucleotides long occurs approximately 3 times. Specific oligonucleotides that are 20 and 25 nucleotides in length occur at an approximate frequency of 0.003 and 0.000003, respectively.
Although the precise frequencies vary from these examples because of the simplified assumptions regarding base abundance and the independence of sequence at a specific residue from sequence at neighboring residues, these rough estimates demonstrate that a specific 20-residue sequence is very likely to be unique in the human genome.
THERMOSTABLE DNA POLYMERASES AND SYNTHETIC OLIGONUCLEOTIDES — The existence of thermostable DNA polymerases, purified or cloned from microorganisms living in hot springs, is a necessary component of PCR. These polymerases can withstand heating to 95 degrees C with minimal loss of activity and function optimally near 70 degrees C. The ability to readily and inexpensively synthesize specific oligonucleotides of 20 to 30 residues is the other technical underpinning of PCR.
PROCESS OF PCR — A reaction mixture containing a large excess of a pair of oligonucleotide primers designed to match either end of the target sequence, a substrate DNA, free deoxynucleotide triphosphates, and a thermostable DNA polymerase is assembled. The mixture is heated to 95 degrees C to allow the double stranded substrate DNA to denature into single strands. The mixture is then cooled to a temperature just below the predicted denaturation temperature of the primers, which will then anneal to the single-stranded substrate DNA and prime new DNA synthesis by the included DNA polymerase. The temperature is then raised to the optimal temperature for the polymerase to allow chain elongation to proceed long enough for synthesis to extend past the opposite primer's complementary sequence. The mixture is then heated to 95 degrees C again in order to once again separate all the DNA to single strands, and the entire sequence of temperature cycling is repeated. Now, the number of potential targets for primer annealing has been doubled, as both the original substrate DNA and the newly synthesized strands are available. In general, between 25 and 40 such cycles of denaturation, annealing, and elongation are performed, resulting in exponential amplification of the target sequence.
Early experiments were performed by physically moving reactions among three water baths preset to the desired temperatures. Currently, a variety of automated thermal cyclers perform the desired temperature regulation with minimal operator hands-on time. All the components of the reactions are readily available commercially, and computer programs that facilitate primer design and calculate annealing temperatures are freely distributed on-line [1-3].
OVERVIEW OF RESEARCH APPLICATIONS — PCR's impact on biomedical research has been immense. This technology allows large quantities of rare sequences to be synthesized, cloned, and analyzed with high reliability and minimum effort. The award of the 1993 Nobel Prize in Chemistry to Kary B. Mullis for inventing the technique recognized the importance of PCR-based methods. A few examples of common research applications of PCR are briefly described below.
PCR is a central tool in genomics and genetics. Relatively early in the human genome project, it was recognized that PCR technology permits more extensive and easier sharing of reagents than had been possible previously. To share a clone, for example, investigators need only specify a pair of primer sequences, the size of the expected product, and buffer conditions for its successful amplification. Any laboratory receiving this information subsequently has the capability of amplifying the sequence from genomic DNA and cloning it into a suitable vector [4]. This is obviously much easier than exchanging actual specimens or cultures.
Amplification of genomic DNA — Two examples of amplification of genomic DNA by PCR will briefly be presented. These are genotyping at microsatellite markers and detection of rare sequences. Both of these examples are fairly common research applications and are likely to be adapted to the clinical setting in the near future.
Microsatellite genotyping — To provide genetic markers, primer pairs flanking short, repetitive sequences called microsatellites were chosen. These were found to be present in variable numbers of copies at a population level, but to display Mendelian inheritance within families. Copy number of the repetitive sequence within the amplified product can therefore define various alleles, while the unique primers define a specific genomic location. This is discussed more extensively in the topic review on repetitive DNA sequences. (See "Repetitive DNA").
Detection of rare sequences — PCR technology has also allowed detection of rare DNA sequences in a population of DNA molecules. This application is particularly prominent in searching for DNA rearrangements in the setting of neoplasia. An example is the discovery that a Herpes simplex-related virus is involved in the pathogenesis of Kaposi's sarcoma [5-7]. Representation difference analysis, a PCR-based method for preferentially amplifying sequences present in one of a pair of sources of substrate DNA [8], has allowed investigators to determine that tumor tissue (but not surrounding normal tissue from the same individuals) harbored integrated viral DNA. Thereafter, primers were designed to allow direct amplification of the viral sequences. (See "Cytogenetic and molecular genetic diagnostic tools" and see "Diagnosis and antiviral therapy of human herpesvirus 8 infection").
Amplification of RNA — PCR can be applied to messenger RNA (mRNA) by addition of a reverse transcription (RT) step prior to amplification. RT-PCR allows detection of rare messages whose abundance is below the detection threshold for Northern blot analysis. Moreover, it is easier and faster to perform. Two examples are expression profiles and RNA virus infection.
Expression profiles — A vast area of current research assesses changes in patterns of gene expression in response to various perturbations. RT-PCR allows qualitative, semi-quantitative, or quantitative measurement of mRNA levels. Qualitative and semi-quantitative assays can now be performed on microarrays, permitting thousands of genes to be studied simultaneously (reviewed by [9-12]).
RNA virus infection — PCR of RNA isolated from blood has become a standard tool in monitoring the viral load in HIV-infected patients (reviewed by [13,14]). This strategy is being extended to other RNA viruses causing chronic infection, such as hepatitis C [15,16]. (See "Techniques and interpretation of HIV-1 RNA quantitation" and see "Diagnostic approach to hepatitis C virus infection").
CRITICAL EVALUATION OF DATA — The ease of performing PCR has led to wide dissemination of the methodology. The rigor with which work is done varies enormously. When reading medical literature including PCR data, one must evaluate the work critically since publication is not a guarantee of high-quality work.
Every PCR experiment requires a minimum of two technical controls, in addition to biological controls specific to the research question being addressed. The technical controls should demonstrate that amplification occurs when it should (positive control) and that it does not occur when it should not (negative control).
In RT-PCR, it is also important to distinguish semi-quantitative from truly quantitative designs. Because substrate concentrations may become limiting in later rounds of amplification, comparing intensity of electrophoretic bands in most circumstances is only semi-quantitative [17,18]. True quantitation generally entails either inclusion of an internal standard that is coamplified competitively with the target or use of special methodology, such as real time PCR [19-22]. (See "Cytogenetic and molecular genetic diagnostic tools")

Polymerase chain reaction

Peptide hormone signal transduction and regulation

INTRODUCTION — Advances in molecular biology over the past 15 years have expanded our understanding of the processes of peptide hormone receptor binding and signal transduction that were previously impossible to study. The DNA sequences for hundreds of receptors and many signaling molecules involved in their regulation have been analyzed.
Signal transduction is a process in which a peptide hormone transfers specific information from the outside of the target cell to exert a cellular response. For this to occur, the hormone (eg, gastrin) exerts a signal through a specific receptor that transmits information from the extracellular compartment (blood) into the cell (acid-secreting cells of the stomach). This message is tightly controlled, especially in settings that are vital for cellular homeostasis.
The normal function of a cell depends upon an intact signal regulation/termination system. If this system malfunctions, the host may experience pathophysiological consequences such as abnormal secretion, motility, growth, or even the development of cancer [1,2].
The major physiological principles of cell signaling systems will be reviewed here. Discussions of individual peptide hormones are presented separately. (See appropriate topic reviews.)
RECEPTOR STIMULATION — Despite the vast array of information communicated to a cell, the basic components of the signaling system are relatively simple (show figure 1). A peptide hormone binds to a cell surface receptor and stimulates activation of an effector system. Cell surface receptors are capable of interacting with only certain chemical messages. The specificity of the hormone-receptor interaction is responsible for the unique cellular response.
The peptide hormone must initiate a change in the receptor such that the hormone-receptor complex activates an intracellular effector molecule such as a specific guanyl-nucleotide-binding protein (G-protein) (show figure 2). Most peptide hormone receptors act through G-proteins; as a result, these receptors are called G protein-coupled receptors (GPCRs).
G proteins — G-proteins are molecular intermediaries that initiate the intracellular communication process (show figure 2) [3,4]. After the hormone binds to its receptor, a G-protein is stimulated. Stimulation begins the intracellular process of signal transduction.
G-proteins are composed of three subunits (alpha, beta, and gamma) and are classified according to their alpha subunit. G-proteins that stimulate adenylyl cyclase are classified as the Gs type; those that inhibit adenylyl cyclase are called Gi. To date, 20 different G-protein alpha subunits have been identified [4].
Shortly after receptor stimulation, a series of events are initiated, which ultimately act to turn off signaling. The principle events in this process involve receptor desensitization and internalization, which reestablish cell responsiveness. (See "Desensitization" below and see "Internalization" below).
G protein-coupled receptors — G protein-coupled receptors are heptahelical proteins, with seven membrane spanning domains [5]. They contain an extracellular amino terminus and an intracellular carboxy terminus (show figure 3). When stimulated by the appropriate chemical messenger, the GPCR undergoes a conformational change that causes coupling to a specific G protein.
GPCRs are classified by their structure into three groups (show table 1). Group I, the largest group, contains the receptors for catecholamines, many peptide hormones, neuropeptides, and glycoproteins. Group II contains the secretin/glucagon/vasoactive intestinal peptide receptor family. Group III contains the metabotrophic receptors (eg, calcium-sensing and glutamate receptors).
Effector systems — Following receptor occupation, G-protein subunits cause activation of enzymes or other proteins, ultimately resulting in a variety of cellular responses (show figure 4). Enzymes, such as adenylyl cyclase or phospholipase C, generate specific second messengers; examples include cyclic adenosine monophosphate (cAMP) and inositol 1,4,5 triphosphate (IP3) and diacylglycerol. Some G-proteins couple directly with specific ion channels, such as potassium or calcium channels, and initiate changes in ion permeability (show figure 4). The effector systems are not understood for some receptors such as receptors involved with cell growth and differentiation (show table 2).
Adenylate cyclase — One of the most studied effector systems of receptor activation is the production of cAMP. As discussed above, Gs coupled G-protein-coupled receptors stimulate adenylate cyclase to produce cAMP. A conformational change occurs as the hormone binds to its receptor allowing the receptor to associate with Gs. Under basal (unstimulated) conditions Gs is bound to GDP. However, GDP is released during hormone binding and is replaced with GTP. The Gs-GTP complex then activates adenylyl cyclase, resulting in the formation of cAMP from ATP within the cytoplasm of the cell. cAMP is then capable of producing other effects within the cell, ultimately leading to responses such as secretion, motility, or growth.
The G alpha-GTP complex is gradually inactivated by GTPase, which converts GTP to GDP. This enzymatic conversion occurs spontaneously by the G-protein, which is itself a GTPase. The conversion of GTP to GDP no longer permits G-protein stimulation of adenylate cyclase and is one way by which the hormone signal is terminated and the basal condition is restored.
Phospholipase C — Other G-proteins, such as Go, activate the phosphoinositide system when bound to hormone. Phospholipase C (PLC) acts on inositol phospholipids found in the cell membrane. As an example, PLC can cause the hydrolysis of phosphatidylinositol 4, 5 bisphosphate (PIP2) to 1, 2 diacylglycerol and inositol 1,4,5 triphosphate (IP3). Diacylglycerol and IP3 can then act as regulators of cell metabolism. This pathway can alter cell function by increasing intracellular calcium levels.
SIGNAL REGULATION AND TERMINATION — Even while signal transduction is occurring, processes begin that will terminate receptor responsiveness.
Desensitization — For the cell to respond to future stimuli, signaling must be terminated completely and in a timely fashion; a process known as desensitization. Desensitization begins within seconds to minutes of hormone binding, and eventually results in signal termination [6].
Desensitization is the primary regulatory step that assures appropriate cell function. It involves the termination of receptor activation by receptor phosphorylation, which is initiated by specific G protein-coupled receptor kinases (GRKs) or second messenger-dependent kinases (eg, protein kinase A and protein kinase C).
Phosphorylation of receptors requires the recruitment of proteins to the hormone-receptor complex, which participate in regulating signaling. One of these is beta-arrestin, which is located in the cytoplasm of unstimulated cells [6]. Upon hormone receptor stimulation, beta-arrestin is translocated from the cytoplasm to the cell membrane and assists in signal termination and subsequent hormone-receptor internalization [6-8].
Internalization — Once the receptor is adequately phosphorylated, the hormone-receptor complex is moves from the cell membrane to the inside of the cell; a process known as "internalization." Internalization, which may also involve beta-arrestins [8], permits receptor processing to occur, which will most likely result in receptor dephosphorylation, removal/degradation of the peptide hormone, and receptor degradation or recycling. Regardless of the eventual fate of the hormone-receptor complex, the goal is to reestablish cell responsiveness, so the next hormone stimulus is capable of sending the necessary information into the cell.
Beta-arrestin — Arrestins are cytosolic proteins that are recruited to hormone bound receptors and bind to cytoplasmic regions of the receptor [9]. Once bound with beta-arrestin, the hormone-receptor complex is "targeted" to a specific endocytic pathway that turns off the signaling process. Endocytosis is the process by which the hormone-occupied receptor is brought from the plasma membrane into the cell. The eventual fate of the receptor depends in part upon the receptor type. Some receptors are rapidly internalized and recycled back to the cell membrane while others are destroyed and only newly produced receptors are expressed on the cell surface.
Non-G protein-coupled receptors
Receptor tyrosine kinases — Some peptides signal through receptors that are not linked to G proteins. One particular class of receptors possesses intrinsic protein tyrosine kinase activity. These receptors are comprised of an extracellular domain that is usually glycosylated, a single transmembrane domain, and a cytoplasmic domain that contains a protein tyrosine kinase region and a region that is a substrate for peptide ligand-activated phosphorylation.
With peptide binding, these receptors either phosphorylate themselves or are phosphorylated by other protein kinases [10]. After activation, these receptors initiate other intracellular signal transduction pathways including Ras that activates MAP kinase. MAP kinase, in turn, modulates other cellular proteins, particularly transcription factors. Specific phosphorylated tyrosine residues are also binding sites for Src homology regions 2 and 3 (SH2 and SH3 domains) that can activate various signaling pathways [11].
Examples of the receptor tyrosine kinase family include receptors for epidermal growth factor, insulin, insulin-like growth factor, fibroblast growth factor, vascular endothelial growth factor, platelet-derived growth factor, nerve growth factor, and macrophage colony stimulating factor [12].
Receptor serine/threonine kinases — Receptor serine/threonine kinases such as TGF-b receptors contain a single transmembrane domain. Stimulation of these receptors activates endogenous serine/ threonine kinase activity which modulates cellular protein function [13].
PATHOPHYSIOLOGIC RELEVANCE — Dysfunction of the control mechanisms of cellular signaling may lead to a number of pathophysiologic consequences [14]. Numerous receptor mutations have been identified that result in unregulated stimulation in the absence of hormone (constitutive activity). As examples, a constitutively active receptor has been found in thyroid adenomas producing clinical hyperthyroidism [15] and in precocious puberty secondary to a mutation in the luteinizing hormone receptor [16]. On the other hand, the McCune-Albright syndrome is due to postzygotic activating mutations in the gene encoding the G alpha s protein, resulting in activation of the signal-transduction pathway generating cyclic AMP [17-19]. The clinical manifestations include polyostotic fibrous dysplasia, cafe au lait spots, and hyperfunction of multiple glands that can lead to sexual precocity, Cushing's syndrome, acromegaly, hyperthyroidism, or hyperparathyroidism.

Peptide hormone signal transduction and regulation

Overview of transcription factors

INTRODUCTION — Transcription is the process whereby the information in genomic DNA is transferred to RNA. The transcription of all genes requires the activity of critical core components that initiate the construction and elongation of RNA. Elements of this basic machinery include the transcription initiation complex and various transcription factors.
The transcription initiation complex consists of multiple molecules, including RNA polymerase II and the TATA binding factor. Most, but not all, genes have a TATA box located approximately 20 and 30 base pairs upstream of the transcription initiation site. This element helps specify the precise site at which transcription is initiated by binding the TATA binding factor. The exact sequence of the TATA box is variable. A number of related thymine and adenine rich sequences all confer TATA box function.
Transcription also requires various additional proteins, named transcription factors, that bind to specific recognition sequences close to the transcription initiation sites. This binding provides a mechanism for tissue- and stimulus-specific gene expression: Tissue-specificity is determined in part by the profile of transcription factors expressed in a given cell type. Stimulus-specificity is partly based upon the occupancy and activation of particular receptors, which leads to transcription factor-mediated alterations in gene expression.
Hundreds of transcription factors have been identified. These factors and their recognition elements are listed on several websites, including TRANSFAC, JASPAR, and TELIS [1-4]. These websites organize transcription factors based upon the presence of specific motifs, such as the following: Leucine zippers (eg, a sequence consisting of a leucine residue at every seventh position) Zinc fingers (eg, the presence of a number of residues - usually four cysteine molecules - that coordinate one zinc ion) Helix-loop-helix (eg, two potential alpha helices connected by a loop of variable length)
Alternatively, the proteins can be characterized based on DNA binding motifs and some databases allow searches based on user-specified features.
An encyclopedic compendium of transcription factors is beyond the scope of this topic review. Instead, the general properties of transcription factors will be presented, followed by a brief review of the specific characteristics of a few, and the consequences of mutations in transcription factors. A review of the basics of molecular biology is presented separately. (See "Overview of molecular biology").
OVERVIEW OF TRANSCRIPTION FACTOR FUNCTION
Properties — Certain characteristics are shared by nearly all transcription factors: All transcription factors bind to short recognition sequences within DNA and interact with the proteins of the transcription machinery. All transcription factors modulate the rate at which their target genes are transcribed. Recent work has demonstrated that the genome contains fewer genes than previously believed and that many genes encode multiple alternative transcripts. Parallel work in stem cell biology and tissue regeneration have revealed the existence of molecular switches that serve to drive cells along various developmental trajectories. These discoveries highlight the importance of transcription factor function in determining cell fate and establishing differentiated expression patterns. Transcription factors may be present in an inactive or active form. In the case of the nuclear hormone receptors, activation occurs after ligand binding. With other transcription factors, such as the signal transduction and activation of transcription proteins (STATs), protein phosphorylation causes activation. Other transcription factors are constitutively active. As an example, Pit-1 is always active, although it is synthesized only in the pituitary gland, presumably as a result of control by other transcription factors [2].
Functions — A cell's developmental fate is a direct consequence of the specific receptors and transcription factors present within the cell when it is exposed to biologically active ligands. An enormous complexity of gene expression results from the combined actions of multiple ligands and receptors triggering downstream signaling via a large array of transcription factors.
The precise mechanisms by which transcription factors help regulate gene expression are not entirely known. A simplified view of this process is shown in the figure (show figure 1): The transcription factor binds to specific sites in the genome via its DNA binding domain. The transcription factor interacts (through additional domains) with other proteins that comprise the transcription initiation complex. The protein-protein interaction between the transcription factor and the initiation complex changes the activity of the initiation complex, resulting in a modification of the rate of transcription.
Assays of function — A commonly used in vitro method to detect the binding of transcription factors to their DNA recognition sites is the "electrophoretic mobility shift assay" or "electrophoretic gel retardation assay" (show figure 2). This assay exploits the property that a DNA-transcription factor protein complex and DNA alone migrate differently on a separating gel matrix, thereby causing a shift or retardation in movement.
The electrophoretic mobility shift assay is used to understand the following properties of transcription factors: What sequences are essential for transcription factor binding Where transcription factor recognition sites are located within specific genes What transcription factors bind to specific recognition sites
TRANSCRIPTION FACTOR MUTATIONS IN DISEASE — Mutations in specific transcription factors can lead to human disease and provide insight into the multi-faceted impact of these proteins. Examples include the transcription factors Runx2 and peroxisome proliferator-activated receptor gamma (PPARg).
Osteoblasts and adipocytes arise from a common precursor found in the bone marrow [5]. To illustrate the role of transcription factors in driving differentiation, this section will briefly review the roles of Runx2 and PPARg in driving the osteoblastic and adipocytic programs, respectively.
Cleidocranial dysplasia — Cleidocranial dysplasia was recognized as a clinical syndrome long before RUNX2 (also called OSF2 and CBFA1) was recognized as the gene mutated in the disorder. The cardinal clinical features of this disorder include delayed closure of cranial sutures, delayed tooth eruption, hypoplastic clavicles, short stature, scoliosis, and multiple additional skeletal abnormalities. Cleidocranial dysplasia is caused by a mutation in RUNX2, a member of the Runx family of transcription factors, located on chromosome 6p21. This single gene is responsible for the initial differentiation of osteoblasts to form skeletal structures [6,7]. (See "Normal skeletal development and regulation of bone formation and resorption").
Linkage mapping revealed heterozygous deletions including the RUNX2 locus in affected families, and sequencing revealed various loss-of-function mutations in additional disease kindreds [7]. A mouse Runx2 knockout leads to features reminiscent of human cleidocranial dysplasia when heterozygous, and lethality at birth when homozygous, with global ossification failure [8]. Both intramembranous and endochondral ossification are disrupted, and mature osteoblastic protein products are not present in the matrix. These findings show that Runx2 serves as a key developmental switch in the osteoblastic lineage.
Runx2 also impacts maturation of the osteoclast and chondrocyte lineages. Osteoclast development requires signals provided by both macrophage colony stimulating factor (M-CSF) and receptor activator of NFkappaB ligand (RANKL), the latter produced by osteoblasts. Osteoclast development is impaired in the Runx2 knockout, while in vitro osteoblast-osteoclast co-culture experiments with Runx2 overexpressing cells show increased RANKL expression and enhanced osteoclastogenesis [8,9]. The effects on osteoclastogenesis show that Rankl is expressed early in the differentiation of the osteoblastic lineage, upstream of another "master" osteoblastic developmental switch, the transcription factor Sp7 (also known as Osterix). Sp7 knockout mice express Runx2, display global failure of skeletal development, but without impairment of osteoclast development [10]. Thus, while Runx2 gene expression is needed for osteoclastogenesis, Sp7 expression is not.
Indian hedgehog (IHH), a paracrine factor that regulates chondrocyte maturation in the growth plate, is also dependent on Runx2. In the absence of Runx2, IHH signaling is diminished, resulting in more rapid chondrocyte maturation and correspondingly decreased chondrocyte proliferation [11]. The cross-talk between Runx2 and IHH accounts for the shortened limb phenotype encountered in cleidocranial dysplasia.
Mutations in the PPAR gamma gene — PPARg is a member of the steroid hormone receptor superfamily and is active as a heterodimer with RXR. This receptor modulates a variety of interrelated processes, including adipogenesis (tontonoz cell 94), insulin sensitivity, lipid peroxidation, lipoprotein transport, and inflammatory cytokine release. It is the target of the currently used thiazolidinedione drugs rosiglitazone and pioglitazone, which act as PPARg agonists [12].
Two isoforms of PPARg are known, PPARg1 and PPARg2. PPARg2 includes an additional 28 N-terminal amino acid residue and is restricted in its expression to the adipocyte lineage [13]. Moreover, this isoform causes increased ligand-independent transcriptional activation [14]. In spite of a decade of intensive study, the natural ligands for PPARg remain incompletely known. Among the potential physiological ligands are 15-deoxy-D12,14 prostaglandin J2, the first identified ligand, an unidentified ligand induced during adipogenesis, and dietary lipids [15-18]. Importantly, PPARg can modulate transcription both in the presence and absence of bound ligand via its interactions with associated coactivator and corepressor proteins. In adipose tissue, PPARg leads to lipid trapping and promotion of the adipocytic differentiation program [19,20]. In liver, macrophages, and other tissues PPARg activation leads to lipid oxidation.
Thiazolidinedione drugs are potent PPARg agonists [21]. Their therapeutic actions include increasing peripheral glucose disposal, leading to marked improvement in insulin sensitivity [22]. The improvement in insulin sensitivity is accompanied by an increase in the mass of adipose tissue and, in a sizable fraction of patients, by fluid retention. As noted above, both adipocytes and osteoblasts arise from a common precursor cell. Given the role of thiazolidinediones in promoting the adipocytic developmental program, it is not surprising that reduced bone formation has been observed in response to the drugs' administration in animal models [23-25]. However, whether similar adverse effects on bone mass occur in humans remains an open question [26,27].
Rare individuals have been reported with dominant-negative PPARg gene mutations. These patients manifest a syndrome that combines lipodystrophy with features of the metabolic syndrome, including insulin resistance, type 2 diabetes, hepatic steatosis, dyslipidemia, hypertension, and polycystic ovary syndrome in women [28-30]. A common P12A polymorphism is associated with type 2 diabetes risk, with the proline allele conferring a relative risk of 1.25 compared to the alanine allele [31]. (See "The metabolic syndrome (insulin resistance syndrome or syndrome X)").
SUMMARY — Transcription factors serve as molecular switches that allow modulation of gene expression and enable a multiplicity of cellular phenotypes to be generated from a limited number of genes. They are critical to both cellular development and responsiveness to physiological and pathological stimuli. Mutations in transcription factors have been identified as causes of syndromic human diseases.

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