HAEMOGLOBINOPATHIES

Introduction to Haemoglobinopathies

HAEMOGLOBIN VARIANTS

1. Sickle syndromes:

i. Sickle-cell trait

ii. Sickle-cell disease

2. Unstable hemoglobins:

Congenital Heinz body anemia; Hb Zurich 

3. Hemoglobins with abnormal oxygen affinity:

i. High affinity- Polycythemia (familial): Hb Chesapeake

ii. Low affinity- Cyanosis (familial): HbM

4. Structural variations leading to thalassemia:

i. Alpha thalassemia- Hb Constant spring

ii. Beta thalassemia- Hb Quong sze

5. Non-symptomatic hemoglobin variants: 

HbP, Q, N, J, etc.

PROPERTIES OF THE
HUMAN HEMOGLOBINS

  • Haemoglobin critical‐ oxygen delivery
  • Can alter red cell shape, deformability, and viscosity
  • Tetramer- Bind upto 4 O2
  • 2α chains (141 amino acids) & 2β chains (146 amino  acids)

PROPERTIES OF THE
HUMAN HEMOGLOBINS

  • HbA1 (α2 β2)‐ Major Adult
  • HbA2 (α2δ2)‐ Minor
  • HbF (α2γ2)
  • Haemoglobin Tetramer‐ Highly soluble but individual globin  chains are insoluble
  • Unpaired globin precipitates, forming inclusions that damage the cell

FUNCTION OF HAEMOGLOBIN

  • Oxygen transport
  • Bind O2 efficiently & retain at high O2 tension  (alveolus)
  • Release at low O2 tension (tissue)
  • Cooperativity or heme‐heme interaction
  • Bohr effect (ability of haemoglobin to deliver more oxygen to tissues at  low pH)

HEMOGLOBIN‐OXYGEN DISSOCIATION  CURVE

CLASSIFICATION OF HEMOGLOBINOPATHIES

  1. Structural Hemoglobinopathies: Hemoglobins with altered amino acid  sequences e.g., HbS
  2. Thalassemias: Defective biosynthesis of globin chains
  3. Thalassemic Hemoglobin Variants: Structurally abnormal Hb associated  with co‐inherited thalassemic phenotype HbE, Hb Constant Spring, Hb  Lepore
  4. Hereditary Persistence of Fetal Hemoglobin
  5. Acquired Hemoglobinopathies:

i. Methemoglobin

ii. Sulfhemoglobin

iii. Carboxyhemoglobin

iv. HbH in erythroleukemia

SICKLE CELL SYNDROME (Haemoglobinopathies)

  • Mutation in β globin gene that changes sixth amino acid from  glutamic acid to valine
  • HbS polymerises reversibly when deoxygenated, to form a  gelatinous network of fibrous polymer that stiffens the  erythrocyte membrane, ↑viscosity 

These changes produce  characteristic sickle shape‐ prone to hemolysis

  • Classification:

Homozygous SS Sickle Cell Anaemia

Heterozygous AS Sickle Cell Trait (generally asymptomatic –  protects against falciparum malaria)

FACTORS INCREASING SICKLING

  • Hypoxia
  • Low pH
  • Fever
  • Infection
  • Excess exercise
  • Anxiety, dehydration
  • Abrupt temperature changes

PATHOPHYSIOLOGY
OF SICKLE CELL CRISIS

CLINICAL FEATURES

  • Anaemia
  • Jaundice
  • Splenomegaly
  • Painful swelling in hands & feet
  • Chronic lower leg ulcers probably arise from ischemia and  super infection in the distal circulation
  • Constitutional symptoms: 

i. Impaired growth

ii. ↑ Susceptibility to infection

CLINICAL FEATURES

  • Vasooclusive phenomenon
  • Microinfarct- abdomen, chest pain, back pain, joints (recurrent  painful crisis)
  • These recurrent episodes, called painful crisis, are the most  common clinical manifestation
  • Macroinfarct- splenic sequestration crisis
  • Bone marrow infarct
    • Bone aseptic necrosis, osteomyelitis
    • Renal cortical necrosis 
    • Retinal damage 
    • Skin ulcers
    • Acute chest syndrome

INVESTIGATION

  • Diagnosis is usually established in childhood
  • Childhood history
  • Hemolytic anemia
  • Granulocytosis
  • RBC morphology‐ Sickle cell, Target cell, Howell‐jolly body
  • Intermittent episodes of ischemic pain
  • Diagnostic test- Sickling test +ve with reducing substance such as  sodium metabisulfite
  • Hb electrophoresis (HbS)

TREATMENT

  • Patient require ongoing continuity of care
  • Education and familiarity with pattern of symptoms provide  the best safeguard
  • Treatment of precipitating factors
  • Preventive measures‐ regular slit‐lamp examinations
  • Antibiotic prophylaxis appropriate for splenectomized  patients during dental or other invasive procedures
  • Vigorous oral hydration during or in anticipation of periods of  extreme exercise, exposure to heat or cold, emotional stress,  or infection
  • Pneumococcal and Haemophilus influenzae vaccines.
  • Hydroxyurea:
    • 10–30 mg/kg per day 
    • Increases fetal hemoglobin  and may also exert beneficial affects on RBC hydration, vascular wall  adherence, and suppression of the granulocyte and reticulocyte counts;  dosage is titrated to maintain a white cell count between 5000 and 8000  per L
  • BMT:
    • Definitive cures known to be effective and safe only in  children. Prognostic features justifying bone marrow transplant are the  presence of repeated crises early in life, a high neutrophil count, or the  development of hand‐foot syndrome
  • Gene therapy

THALASSEMIA SYNDROME (Haemoglobinopathies)

  • Hemoglobin consist of 2α & 2β peptide chains
  • HbA 95% – α2β2
  • HbA2 5% ‐ α2 δ2
  • Fetal HbF ‐ α2 γ2

(may persist in β thalassemia)

  • At birth, Hb F appx. 80 % and Hb A- 20 %.
  • By approximately six months of age, healthy infants will have transitioned to 
    • Mostly Hb A, 
    • A small amount of HbA2, and  
    • Negligible Hb F

BLOOD FILM
OF THALASSEMIA

EPIDEMIOLOGY

  • Affects men and women equally and occurs in approximately 4.4 of every10,000 live births
  • Alpha thalassemia occurs most often in persons of African and  Southeast Asian descent
  • Beta thalassemia is most common in persons of  Mediterranean, African, and Southeast Asian descent
  • Thalassemia trait affects 5 to 30 percent of persons in these  ethnic groups

ALPHA THALASSEMIA

  • Alpha thalassemia is the result of deficient or absent  synthesis of alpha globin chains, leading to excess beta  globin chains
  • Alpha globin chain production is controlled by  two genes on each chromosome 16

BETA THALASSEMIA

  • Beta thalassemia is the result of deficient or absent  synthesis of beta globin chains, leading to excess alpha  chains
  • Beta globin synthesis is controlled by one gene on  each chromosome 11

CLASSIFICATION OF THALASSEMIA

α‐ THALASSEMIAS

  • Hb Barts‐ Hydrops Foetalis
  • Deletion of all four α chain genes
  • Total suppression of α globin chain synthesis
  • Most severe form (Homozygous state)
  • Incompatible with life
  • Diagnosis‐ Lab picture of severe HA
  • Hb‐ Electrophoresis‐ Hb Barts‐ diagnostic

Hb‐H disease

  • Deletion of three α‐chain genes
  • Hb‐H β‐globin chain tetramer (β4)
  • Markedly impaired α‐chain synthesis
  • Clinical feature‐ s/o HA
  • Lab‐ Hemolytic Anemia, Heinz bodies (brilliant cresyl  blue stain)
  • Diagnostic‐ Hb‐ Electrophoresis

β‐ THALASSEMIAS

  • β‐ Thalassemia Major
  • Common form of congenital anemia
  • Homozygous form characterized by complete absence of β chain synthesis
  • Diagnosis‐ Lab picture of severe HA
  • Hb‐ Electrophoresis‐ HbF &
    HbA2‐ Diagnostic

SEVERITY OF
β-THALASSEMIA

CLINICAL FEATURES

  • Anemia
  • Marked hepatosplenomegaly
  • Marrow hyperplasia, frontal bossing & prominent malar eminence
  • Chipmunk facies, thalassemic facies
  • Iron overload
  • Growth retardation
  • Delayed puberty, DM
  • Cardiomegaly

CHIPMUNK FACIES, THALASSEMIC FACIES

TIME OF COMPLICATIONS OF  THALASSEMIA

DIAGNOSIS

  • Most persons with thalassemia trait are found  incidentally when their complete blood count shows a  mild microcytic anemia
  • Microcytic anemia can be caused by:
  1. Iron deficiency  
  2. Thalassemia
  3. Lead poisoning  
  4. Sideroblastic anemia  
  5. Anemia of chronic disease

SUPPLEMENTAL TESTS

  • Include:
  • Serum ferritin
  • The peripheral smear
  • Hemoglobin electrophoresis
  • Serum lead level
  • Rarely bone marrow aspirate

THE HEMOGLOBIN ELECTROPHORESIS

TREATMENT

  • Blood transfusion to maintain hematocrit
  • Folate supplementation
  • Avoid iron therapy
  • Desferrioxamine for iron chelation
  • Splenectomy
  • Allogenic bone marrow transplantation
  • Gene therapy
  • Antenatal diagnosis of thalassemia syndromes is now widely  available.
  • DNA diagnosis is based on PCR amplification of fetal DNA,  obtained by amniocentesis or chorionic villus biopsy

PREVENTION

  • Blood tests and family genetic studies can  show whether an individual has  thalassemia or is a carrier
  • A genetic counselor can detail the family  background, discuss risks

Other Biochemistry Notes

. Biochemistry of Proteins

Carbohydrate Metabolism

VITAMIN PYRIDOXINE AND BIOTIN

Vitamin A

Pyrimidine metabolism

Purine Metabolism

Cardiac Biomarkers

VITAMIN D

. Blood Metabolism (Heme synthesis and breakdown)

DNA Repair

Regulation of gene expression

DNA Replication

Transcription

All books/videos/software featured here are free and NOT HOSTED ON OUR WEBSITE. If you feel that your copyrights have been violated, then please contact us immediately.

Contact us: medicalfarre@gmail.com

218 thoughts on “HAEMOGLOBINOPATHIES”

  1. Pingback: munsters pinball machine

  2. scoliosis
    Hi there to all, it’s actually a nice for me to pay a visit this
    website, it includes precious Information. scoliosis

  3. Pingback: Buy Opana 10 mg online

  4. That is a very good tip particularly to those fresh to the blogosphere. Brief but very precise informationÖ Many thanks for sharing this one. A must read article!

  5. Pingback: nanaimo bc

  6. Pingback: nasstoys anal plugs

  7. scoliosis
    I’m not sure where you’re getting your information, but good topic.
    I needs to spend some time learning more or understanding more.
    Thanks for great information I was looking for
    this information for my mission. scoliosis

  8. Pingback: Vortex Venom

  9. I’d like to thank you for the efforts you have put in penning this blog. I am hoping to see the same high-grade content from you in the future as well. In truth, your creative writing abilities has motivated me to get my own, personal blog now 😉

  10. I really love your website.. Very nice colors & theme. Did you develop this site yourself? Please reply back as Iím planning to create my very own website and would love to know where you got this from or exactly what the theme is called. Kudos!

  11. Pingback: gas fireplace

  12. Pingback: bàn học cho bé

  13. Oh my goodness! Amazing article dude! Thank you so much, However I am having troubles with your RSS. I donít know why I am unable to join it. Is there anyone else getting identical RSS problems? Anybody who knows the solution can you kindly respond? Thanks!!

  14. I blog often and I seriously thank you for your content. This article has truly peaked my interest. I will bookmark your website and keep checking for new information about once a week. I subscribed to your RSS feed too.

  15. scoliosis
    It is appropriate time to make a few plans for the long run and it’s time to be happy.
    I’ve learn this put up and if I could I desire to
    suggest you some attention-grabbing issues
    or tips. Perhaps you can write subsequent articles referring
    to this article. I desire to learn even more issues about
    it! scoliosis

  16. Howdy! I could have sworn Iíve been to this website before but after going through a few of the articles I realized itís new to me. Anyhow, Iím definitely delighted I came across it and Iíll be bookmarking it and checking back often!

  17. Pingback: Architectural design

  18. Oh my goodness! Awesome article dude! Thanks, However I am having issues with your RSS. I donít understand the reason why I can’t subscribe to it. Is there anyone else getting the same RSS issues? Anyone who knows the solution can you kindly respond? Thanx!!

  19. dating sites
    Do you mind if I quote a couple of your posts as long as
    I provide credit and sources back to your website? My blog is in the very same niche as yours and
    my visitors would truly benefit from a lot of the information you present here.

    Please let me know if this okay with you. Many thanks!
    dating sites

  20. Aw, this was an incredibly good post. Taking the time and actual effort to produce a top notch articleÖ but what can I sayÖ I hesitate a lot and never seem to get anything done.

  21. You’ve made some really good points there. I checked on the internet to
    find out more about the issue and found most people will go along with your views on this site.

  22. May I just say what a comfort to find an individual who actually knows what they are talking about online. You actually know how to bring an issue to light and make it important. More and more people need to check this out and understand this side of the story. I can’t believe you are not more popular because you most certainly possess the gift.

  23. Pingback: شركة كشف تسربات المياه بالرياض

  24. After I initially left a comment I appear to have clicked on the -Notify me when new comments are added- checkbox and from now on whenever a comment is added I receive 4 emails with the same comment. Perhaps there is a means you can remove me from that service? Thank you!

  25. Wonderful blog! Do you have any recommendations for aspiring writers? I’m planning to start my own blog soon but I’m a little lost on everything. Would you suggest starting with a free platform like WordPress or go for a paid option? There are so many choices out there that I’m completely confused .. Any suggestions? Thanks a lot!

  26. You made some really good points there. I looked on the net for additional information about the issue and found most people will go along with your views on this web site.

  27. Pingback: tepeustu escort

  28. Pingback: how to spank properly

  29. Pingback: vibrators

  30. After exploring a number of the blog articles on your web site, I seriously appreciate your way of writing a blog. I bookmarked it to my bookmark webpage list and will be checking back in the near future. Please check out my website too and let me know how you feel.

  31. Hi, I do think this is a great website. I stumbledupon it 😉 I will return once again since i have saved as a favorite it. Money and freedom is the best way to change, may you be rich and continue to guide other people.

  32. Hello, i feel that i saw you visited my site so i got
    here to return the desire?.I am attempting to find issues to enhance
    my web site!I assume its good enough to use a few of your ideas!!

  33. Hi, I do think this is an excellent site. I stumbledupon it 😉 I’m going to come back yet again since i have book marked it. Money and freedom is the greatest way to change, may you be rich and continue to guide other people.

  34. I’m more than happy to find this page. I need to to thank you for your time due to this wonderful read!! I definitely appreciated every part of it and i also have you book-marked to check out new things in your website.

  35. Pingback: נערות ליווי בחיפה

  36. Pingback: deuterium gas for sale

  37. Pingback: huge squirting dildo

  38. Pingback: mobile homes for rent in sanford florida

  39. Good post. I learn something totally new and challenging on blogs I stumbleupon on a daily basis. It will always be useful to read articles from other authors and use a little something from their sites.

  40. Pingback: porn

  41. You’ve made some decent points there. I looked on the web for additional information about the issue and found most people will go along with your views on this site.

  42. Pingback: guns for sale under 350

  43. Pingback: mobile homes for sale in westmoreland county pa

  44. You’ve made some really good points there. I checked on the web for more info about the issue and found most individuals will go along with your views on this website.

  45. I blog quite often and I really appreciate your information. This great article has really peaked my interest. I’m going to book mark your blog and keep checking for new information about once a week. I subscribed to your Feed too.

  46. Pingback: first sex toys

  47. Pingback: bizarre dildo

  48. It’s actually a cool and useful piece of information.
    I’m glad that you simply shared this useful information with us.
    Please stay us up to date like this. Thank you for sharing.

  49. Pingback: realistic dildo

  50. Who needs to devote hours and hours grinding in the game to receive just a few resources? Right now you too can make use of a free game hack that provides you infinite resources on any sort of action game without having to grind endless hours! Our on-line cheats will offer you with endless coins, diamonds, or other kind of in-game item that is required to win. By using our game hacks, your gaming adventure will be less about numbers and more about fun! Take the chance right now to employ our brand-new working action game cheats that will certainly give you endless resources!

  51. Thank you for some other excellent post. Where else may just anybody get that type of info in such an ideal manner of writing? I’ve a presentation next week, and I am on the look for such info.|

  52. Very nice post. I just stumbled upon your blog and wanted to say that I’ve truly enjoyed surfing around your blog
    posts. In any case I will be subscribing to your feed and I hope you write again soon!

  53. Nice post. I learn something new and challenging on sites I stumbleupon on a daily basis. It’s always exciting to read through content from other writers and use a little something from their web sites.

  54. Your style is unique in comparison to other people I’ve read stuff from. Many thanks for posting when you have the opportunity, Guess I will just book mark this page.

  55. Your Online Metal Marketplace In Texas With Lowest Prices, Guaranteed. Thousands of Steel Items Available, Custom or Stock. Call Our Experts, Shop Steel Now

  56. Pingback: male sex toys

  57. Hello there, I believe your blog might be having internet browser compatibility issues. Whenever I take a look at your web site in Safari, it looks fine however when opening in I.E., it’s got some overlapping issues. I merely wanted to give you a quick heads up! Aside from that, excellent website!

  58. I’ve been surfing online more than three hours these days, yet I by no means
    found any fascinating article like yours. It is
    pretty worth enough for me. In my view, if all site owners
    and bloggers made excellent content as you probably
    did, the net will be a lot more helpful than ever before.

  59. When I initially left a comment I appear to have clicked on the -Notify me when new comments are added- checkbox and from now on every time a comment is added I get 4 emails with the same comment. Perhaps there is an easy method you can remove me from that service? Thanks!

  60. Pingback: Glock 17 gen 5 for sale

  61. Pingback: fn 509 tactical

  62. Pingback: virtual card buy

  63. Pingback: bayan eskort maltepe

  64. Pingback: escort istanbul pendik

  65. Oh my goodness! Impressive article dude! Thank you, However I am having troubles with your RSS. I donít understand why I cannot join it. Is there anybody else having the same RSS problems? Anyone that knows the answer can you kindly respond? Thanks!!

  66. Pingback: online pharmacy canada

  67. Pingback: guns for sale

  68. Pingback: healthplanscanada.ca

  69. An impressive share! I’ve just forwarded this onto a friend who has been doing a little homework on this. And he actually bought me dinner because I found it for him… lol. So allow me to reword this…. Thank YOU for the meal!! But yeah, thanks for spending time to discuss this topic here on your site.

  70. Pingback: slot online

  71. A motivating discussion is definitely worth comment. I do believe that you should publish more on this topic, it may not be a taboo subject but typically people do not talk about these topics. To the next! Cheers!!

  72. Hi, I do think this is a great website. I stumbledupon it 😉 I will revisit yet again since I book-marked it. Money and freedom is the greatest way to change, may you be rich and continue to help other people.

  73. Pingback: misconceptions about sex

  74. Pingback: best clitoral stimulator

  75. The next time I read a blog, I hope that it does not disappoint me just as much as this particular one. I mean, Yes, it was my choice to read, however I actually believed you’d have something helpful to talk about. All I hear is a bunch of complaining about something that you can fix if you weren’t too busy looking for attention.

  76. You made some really good points there. I checked on the net to learn more about the issue and found most people will go along with your views on this web site.

  77. Hello there, I believe your web site could be having web browser compatibility problems. When I look at your web site in Safari, it looks fine but when opening in Internet Explorer, it has some overlapping issues. I just wanted to give you a quick heads up! Besides that, great site!

  78. This is the right web site for anybody who wants to find out about this topic. You know a whole lot its almost tough to argue with you (not that I actually will need toÖHaHa). You certainly put a brand new spin on a topic that has been written about for a long time. Wonderful stuff, just wonderful!

  79. Iím amazed, I have to admit. Seldom do I encounter a blog thatís both educative and amusing, and without a doubt, you’ve hit the nail on the head. The issue is something not enough men and women are speaking intelligently about. I am very happy that I stumbled across this during my search for something concerning this.

  80. Pingback: shopping challenge

  81. Pingback: buy kratom

  82. Pingback: whopper dildo

  83. Iím amazed, I must say. Seldom do I encounter a blog thatís equally educative and amusing, and without a doubt, you’ve hit the nail on the head. The issue is something that too few folks are speaking intelligently about. Now i’m very happy that I came across this during my hunt for something regarding this.

  84. Pingback: Hair salon/s

  85. Pingback: Buy Weed Online

  86. Oh my goodness! Awesome article dude! Thanks, However I am experiencing problems with your RSS. I donít know the reason why I am unable to join it. Is there anybody having identical RSS issues? Anybody who knows the solution can you kindly respond? Thanks!!

  87. Pingback: strap on for beginners

  88. A motivating discussion is worth comment. I do think that you should publish more about this subject matter, it might not be a taboo subject but generally people do not talk about these subjects. To the next! Kind regards!!

  89. Pingback: adam and eve sex toys

  90. Pingback: male prostate massager

  91. Nice post. I learn something new and challenging on blogs I stumbleupon on a daily basis. It’s always exciting to read articles from other authors and practice a little something from other websites.

  92. Oh my goodness! Impressive article dude! Thank you, However I am having problems with your RSS. I donít know why I can’t join it. Is there anyone else having similar RSS problems? Anyone who knows the solution will you kindly respond? Thanks!!

  93. Nice post. I learn something totally new and challenging on websites I stumbleupon every day. It’s always helpful to read through content from other writers and practice a little something from their websites.

  94. Good post. I learn something totally new and challenging on blogs I stumbleupon everyday. It’s always interesting to read through content from other authors and practice something from other websites.

  95. Having read this I believed it was very enlightening. I appreciate you spending some time and effort to put this short article together. I once again find myself personally spending a significant amount of time both reading and leaving comments. But so what, it was still worthwhile!

  96. I must thank you for the efforts you’ve put in writing this blog. I’m hoping to check out the same high-grade content from you later on as well. In fact, your creative writing abilities has encouraged me to get my very own website now 😉

  97. Aw, this was a really good post. Taking the time and actual effort to create a great articleÖ but what can I sayÖ I put things off a whole lot and never manage to get nearly anything done.

  98. A fascinating discussion is worth comment. I think that you need to write more about this subject matter, it may not be a taboo matter but usually people don’t discuss these issues. To the next! Cheers!!

  99. Greetings! Very helpful advice within this article! It is the little changes that will make the most significant changes. Many thanks for sharing!

  100. I have to thank you for the efforts you’ve put in penning this site. I am hoping to check out the same high-grade blog posts from you later on as well. In fact, your creative writing abilities has inspired me to get my own blog now 😉

  101. A fascinating discussion is worth comment. I think that you need to publish more on this subject matter, it may not be a taboo matter but usually people do not speak about these subjects. To the next! Cheers!!

  102. Oh my goodness! Impressive article dude! Thanks, However I am going through issues with your RSS. I donít know the reason why I cannot subscribe to it. Is there anybody else getting identical RSS issues? Anyone who knows the answer will you kindly respond? Thanx!!

  103. Pingback: super bikes 2 arcade

  104. Pingback: g gasm curve

  105. Hi, I do think this is a great blog. I stumbledupon it 😉 I am going to revisit yet again since i have book marked it. Money and freedom is the greatest way to change, may you be rich and continue to help others.

  106. Pingback: Pinball machines

  107. An impressive share! I have just forwarded this onto a coworker who had been doing a little research on this. And he in fact bought me breakfast simply because I stumbled upon it for him… lol. So allow me to reword this…. Thank YOU for the meal!! But yeah, thanks for spending time to talk about this topic here on your site.

  108. Pingback: dungeness crab for sale

  109. Pingback: GOLDEN RETRIEVER PUPPIES FOR SALE

  110. Pingback: PARROTS FOR SALE

  111. Pingback: Pound of Weed

  112. Iím impressed, I must say. Rarely do I come across a blog thatís equally educative and interesting, and without a doubt, you’ve hit the nail on the head. The problem is something that not enough men and women are speaking intelligently about. I am very happy that I found this in my hunt for something concerning this.

  113. Pingback: software review

  114. An impressive share! I’ve just forwarded this onto a co-worker who was doing a little research on this. And he actually ordered me dinner because I discovered it for him… lol. So allow me to reword this…. Thank YOU for the meal!! But yeah, thanks for spending some time to talk about this issue here on your site.

  115. Hi, I do think this is a great blog. I stumbledupon it 😉 I will come back once again since i have book marked it. Money and freedom is the greatest way to change, may you be rich and continue to guide others.

  116. Pingback: PULVERIZER

  117. Your style is so unique compared to other people I have read stuff from. Thank you for posting when you’ve got the opportunity, Guess I will just book mark this site.

  118. You are so interesting! I don’t think I have read through a single thing like that before. So nice to discover another person with a few unique thoughts on this issue. Seriously.. thank you for starting this up. This site is something that’s needed on the web, someone with some originality!

  119. You are so interesting! I don’t think I have read a single thing like this before. So nice to find somebody with some genuine thoughts on this subject. Really.. thank you for starting this up. This website is something that is needed on the web, someone with a little originality!

  120. Can I just say what a comfort to find somebody that really understands what they are talking about on the internet. You certainly know how to bring an issue to light and make it important. A lot more people must read this and understand this side of your story. It’s surprising you’re not more popular because you certainly have the gift.

  121. Greetings, I do believe your website could possibly be having browser compatibility issues. Whenever I look at your site in Safari, it looks fine however, if opening in IE, it has some overlapping issues. I merely wanted to provide you with a quick heads up! Aside from that, wonderful site!

  122. An interesting discussion is definitely worth comment. There’s no doubt that that you ought to publish more about this subject matter, it might not be a taboo subject but generally folks don’t talk about these subjects. To the next! Kind regards!!

  123. An impressive share! I have just forwarded this onto a coworker who was doing a little research on this. And he actually bought me lunch because I found it for him… lol. So allow me to reword this…. Thank YOU for the meal!! But yeah, thanx for spending some time to talk about this issue here on your blog.

  124. I truly love your website.. Very nice colors & theme. Did you develop this web site yourself? Please reply back as Iím wanting to create my own site and want to learn where you got this from or just what the theme is called. Many thanks!

  125. Iím impressed, I have to admit. Rarely do I come across a blog thatís both equally educative and engaging, and let me tell you, you’ve hit the nail on the head. The issue is something which not enough men and women are speaking intelligently about. I am very happy that I stumbled across this in my hunt for something regarding this.

  126. Can I just say what a comfort to uncover somebody who actually knows what they’re talking about on the web. You definitely understand how to bring an issue to light and make it important. A lot more people have to read this and understand this side of the story. It’s surprising you aren’t more popular given that you certainly have the gift.

  127. Howdy! I could have sworn Iíve visited your blog before but after looking at some of the posts I realized itís new to me. Anyhow, Iím definitely happy I found it and Iíll be book-marking it and checking back frequently!

  128. An interesting discussion is worth comment. I do believe that you need to publish more on this subject, it might not be a taboo subject but usually people do not discuss such subjects. To the next! Best wishes!!

  129. Hi there! This article could not be written any better! Reading through this article reminds me of my previous roommate! He continually kept preaching about this. I most certainly will send this post to him. Pretty sure he’ll have a great read. Thank you for sharing!

  130. After looking over a few of the blog posts on your web site, I really appreciate your way of writing a blog. I saved it to my bookmark website list and will be checking back soon. Please check out my web site as well and let me know your opinion.

  131. Hi there! This blog post couldnít be written much better! Going through this article reminds me of my previous roommate! He constantly kept talking about this. I am going to send this information to him. Pretty sure he’ll have a great read. Thank you for sharing!

  132. Good post. I learn something totally new and challenging on websites I stumbleupon on a daily basis. It’s always helpful to read content from other writers and use a little something from their web sites.

  133. Ahaa, its good dialogue about this paragraph here at this weblog, I have read all that, so at this time me also commenting here.

  134. Greetings! Very helpful advice in this particular article! It is the little changes that will make the biggest changes. Many thanks for sharing!

  135. Pingback: where to buy kratom

Leave a Comment

Your email address will not be published.