Arthritis (बातज्वर), Molecular Mechanism of Pathogenesis

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View my previous abstract post on Pathogenesis of Arthritis

Cannot Nobel prize be awarded for Windows OS, Google or Facebook ?

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Announcement of Nobel prize soothed pounding of many people. Although no Nepali has been awarded, Nobel prize is the subject in the gossip of literate Nepali. Nobel prize has been becoming the dream and destination not only for scientists but also for politicians, economists, writers and so on. Nobel prize is intended for new discovery, or significant contributor who made life easier and well organized society.

The first step in the discovery of theory or science is the designing of research through literature search. Some search engines certainly have signified and accelerated in this process. There are many search engines, and Google is the widely used and popular. Google search engine script was discovered by Larry Page and Sergey Brin as PhD candidates at Stanford University. 

Analysis and data interpretation of research and experiments needs software for promptness and accuracy. The software needs good platform to be installed. Bill Gates and his colleagues had discovered and developed the popular operating system (OS), DOS, Windows. Mac OS, Unix, Linux, FreeBSD, etc. are the other OS, but still they  are not as popular, and easier as Windows OS. In addition, Microsoft has developed the office packages (Word, Excel, PowerPoint, etc.), which are also essential in research. Nobel prize in Physics has been awarded for research of hard disk miniaturization (2007), and development of integrated circuits (2000), which are essential part of computer hardware. I think, Software developer also has the similar type of contribution and deserves for the Nobel prize. 

Facebook and twitter, however, are not essential in the scientific study, but they are popular among the community and  are good medium to increase the relationship and information. And Facebook is the top web page based on the number of users everyday.

In my opinion, the famous novel, Harry Porter, Miscrosoft OS, Google, Facebook, Twitter, or their designer deserve Nobel prize in literature. Probably, there would be a policy, not to award Nobel prize who had gained popularity and money.

If Nobel prize is awarded for these computer applications, which category would be appropriate for them? Physics, due to the scripts design and engineering? Economics, as these are among top revenue generating companies? Peace,  because Facebook and Twitter had played an important role to dethrone the tyrant of Egypt and other countries. some people may think reverse of it, people agitated and involved in violence due to Facebook and Twitter.

Medicinal Plants in Nepal, Acorus calamus (बोझो)

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Since antiquity, man kind has been using plants to treat many diseases and some of these traditional medicines are still included as part of the habitual treatment of various maladies. Nepal also has been relying on locally available medicinal plants and in some remote area of Nepal, still there is few option for modern allopathic treatment. I am posting in serial, some of these important medicinal plants that are frequently used.

Acorus calamus L. (English: Sweet flag; Nepali: बोझो)
It belongs to the family Araceae. It is an erect herb with aromatic rootstock, leaves broad, ensiform, with distinct midrib. Spathe cylindrical and slightly curved. Flowers: bisexual, each with a perianth of six orbicular concave segments, stamens 6, ovary conical, fruits: oblong berries.
Constituents: Monoterpene hydrocarbons, sequestrine ketones, asarone (2, 4, 5-trimethoxy-1-propenylbenzene), and β-asarone contained in the essential oil distillates from root .
Uses: It is used as an analgesic for the relief of toothache or headache, to cure /prevent a hangover, to treat a cough, as a carminative for colic, to treat diabetes, to reduce bowel pains, to lessen swelling and for constipation, to cure fevers, for asthma and bronchitis, and as sedative. It exhibited a good anti-fungal activity as well.
References:

1. Joshi KK and SD Joshi. Genetic Heritage of Medicinal and Aromatic Plants of Nepal Himalayas. Buddha Academic Publishers and Distributors Pvt. Ltd., Kathmandu, Nepal. P-239 (2001).
2. Bajracharya MB. Ayurvedic Medicinal Plants and General Treatment. Piyusavarsi Ausadhalaya Mahaboudha, Kathmandu, Nepal. P-230 (1979).
3. Devkota KP, R Acharya, MP Baral and RP Adhikari.  Antimicrobial activities of some herbal plants used in traditional medicine in Nepal. In: Proceding of 3rd national conference on science and technology. Vol 2: 1311-1317. (1999).

contd....

महिलाहरुमा autoimmune रोगको सम्भावना ज्यादा हुने कारण

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चालिस बर्ष उमेरपछिको स्थिती हेर्ने हो भने, पुरुषलाई भन्दा महिलालाई auto-immune रोग लाग्ने सम्भावना तीन गुणा धेरै हुन्छ । अहिले सम्म पाइएको तथ्याङ्क अनुसार, महिला : पुरुष = ३:१ छ । मेरो लेख, Auto-immune रोग के हो त ? हालसालै गरिएको अध्य्यन अनुसार महिलाहरुमा auto-immune रोगको सम्भावना ज्यादा हुने निम्न कारणहरु पत्ता लागेका छन् ।

1. Estrogens (oestrogens) हार्मोन महिलाहरुमा उत्पादन हुन्छ भने पुरुषहरुमा testosterone हार्मोन । estrogens हार्मोनले immune system ज्यादा सकृय हुन उत्प्रेरणा दिन्छ ।
2. मानव शरीरमा २३ जोडा अनुबशिंक तत्वहरु (chromosomes) हुन्छन् । प्रत्येक जोडामा एक-बाबु तथा एक-आमाबाट आएका हुन्छन् । पुरुष र महिलामा २२ जोडा chromosome एकै किसिमका हुने भएता पनि २३ औं जोडा भने फरक हुन्छ । २३ औं जोडामा XX (महिला), XY (पुरुष)हुन्छ । यहीँ X chromosme मा immune प्रणालीलाई ज्यादा सकृय बनाउने केही रसायनहरु उत्पादन गर्ने अनुबशिंक तत्वका ईकाइहरु (genes) रहेका हुन्छन् । महिलाहरुमा X-chrosome दुइवटा हुनाले पुरुषको तुलनामा यस्ता रसायन हरु पनि दुईगुणा बढी उत्पादन हुन्छन् । हुन त gene दुईगुणा भयो भन्दैमा त्यसको उत्पादन पनि अनावश्यक रुपमा दुईगुणा नै हुन्छ भन्ने त होइन । नचाहिएको एउटा gene लाई छोपेर राख्ने र यस्को उत्पदन हुन नदिने अर्कै प्रणाली हुन्छ, यदी यो प्रणाली बेकार भएमा मात्र महिलाहरुमा autoimmune रोगको सम्भावना ज्यादा हुन्छ।
3. Microchimerism:- गर्भावस्थामा रहेको भ्रुण/बच्चा महिलाको रक्तसंचार प्रणाली सँग प्रत्यक्ष सम्पर्कमा रहेको हुँदैन, साल-नाल को माध्यमबाट अप्रत्यक्ष रुपमा संपर्कमा रहेको हुन्छ । तर, कारणबस महिलाको रक्तसंचार प्रणालीमा बच्चाको कोष, तन्तु इत्यादी आउन पुग्यो भने महिलाको Immune system सकृय भाईहाल्छ । यो सकृयता Helper CD4 T-cell ले स्मरण गरिराखेको हुन्छ जसले महिलालाई बच्चाको जन्म पश्चात पनि हानी पुर्याउँछ । सामान्यत: बच्चाको जन्म पश्चात यस्ता Helper CD4 T-cell आँफैँ नस्ट हुन्छन् ।

रोग प्रतिरोधात्मक प्रणाली ज्यादा सकृय भएर हुने रोगहरु (Autoimmune Diseases)

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हाम्रो शरीरमा बाह्य हानिकारक बस्तुहरु जस्तै: जीवाणु (bacterium), बिषाणु (virus), परजिवी (parasite) इत्यादी प्रवेश हुने बित्तिकै हाम्रो शरीरको रोग प्रतिरोधात्मक प्रणाली (Immune System) सकृय हुन्छ र रोग लाग्न दिदैन । यदि यो प्रणाली कमजोर भयो भने हाम्रो शरीर भित्र प्रवेश गर्ने जीवाणु/ बिषाणु/ परजिवीहरुले तुरुन्त आक्रमण गरिहाल्छन् र हामीलाई रोगहरु जस्तै: झाडा-पखाला, रुघा-खोकी, क्षयरोग, इत्यादी. लाग्छ ।

AIDS वास्तवमा आफैंमा कुनै रोग होइन तर यसले चाँही हाम्रो immune system लाई यती कमजोर बनाइदिन्छ कि निको नै नहुने गरी, अनी सबै किसिमको (सरुवा) रोगहरु लाग्छ र मृत्‍यु हुन्छ ।

तर immune system ज्यादा सकृय अथवा cross reaction भयो भने पनि यसले हाम्रो शरीरका आफ्नै कोष, तन्तु तथा अङ्गहरुलाई आक्रमण गर्न सुरु गर्छ अनी आँफैमा एक रोगको रुप लिन्छ, जसलाई Autoimmune Disease भनिन्छ । यसअन्तर्गत बात (Rheumatoid Arthritis), बिसमज्वर (Rheumatic fever), दम (Allergic Asthma), खास प्रकारको मुटुको रोग (Rheumatic heart disease), Graves' disease, Lupus, Optic neuritis, Pernicious anemia, Sjögren's syndrome, Primary biliary cirrhosism, Myasthenia gravis, Diabetes mellitus type 1, इत्यादी. (यस्ता सय भन्दा बढी किसिमका रोगहरु पत्ता लागेका छन्) ।
क्रमश:

Install LibreOffice in Older Version of Fedora

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As I have been writing (can be found under labels: Linux, Fedora, Computer), Linux OS has been improving in graphical user interface and other packages/applications. OpenOffice, which is one of the powerful application/package, was the Linux equivalent of MS Office (Word, Excel, Power-point, Access, etc.). Recently, OpenOffice has been replaced by LibreOffice in Linux OS probably due to license conflict. In the latest version, Fedora 15, it can installed as;

1. Open terminal, and become root user (type "su" and then type password ".......")
2. Type "yum install libreoffice" OR type "yum groupinstall "Office/Productivity""

In older version of Fedora (bur not older than Fedora 8), we have to

1. Download all the required files here (Other options are available to select there, e.g., to install in Windows, ".exe" file can be selected).
2. Extract the zipped file (mouse-right click and click on "extract here". Careful ! where does this file situated, normally it remains under home/Downloads).
3. Open terminal, and become root user
4. Type "yum localinstall /home/bishnu/Downloads/LibO_3.3.4rc1_Linux_x86_install-rpm_en-US/RPMS/* --nogpg" (after few seconds it will ask for permission, then type "y")
5. Then again type, "rpm -Uvh  /home/bishnu/Downloads/LibO_3.3.4rc1_Linux_x86_install-rpm_en-US/RPMS/desktop-integration/libreoffice3.3-redhat-menus-3.3-401.noarch.rpm --force"

Note: Bishnu can be replaced by your username, or entire /home/bishnu/Downloads can be replaced by actual location of these file. But it will be easier, if we paste this folder (software) under /Downloads, if it was brought from friend's computer/purchased). The file names LibO_3.3.4rc1..... / libreoffice3.3-redhat-menus-3.3-401 are variable with the time.

Nepalese in Reputable Science Journals

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Probably, there might be some articles published by Nepalese in the famous and reputed science journals, such as science, nature, cell, etc.

Recently, Lujendra Ojha, Mhaipi, Kathmandu has discovered the possibilities of water in the Mars. This made him a famous scientist, and he has been covered in all types of media worldwide. He is an undergraduate research intern at lunar and planetary laboratory, University of Arizona, Tucson, USA. He published his finding as second author in one of the most famous journal (Science, 5 Aug 2011, 333 (6043); 740-743, impact factor of this journal is 31.4).

Another two Nepalese (Deepak Koirala and Soma Dhakal) have published their research article as first and second author in one of the most reputed journal (Nature Chemistry, 28 Aug 2011, impact factor of this journal is 17.9). Deepak Koirala, Rupandehi district, was the batch topper in MSc from Central Department of Chemistry (CDC), TU, Nepal.  Soma Dhakal, Palpa district, also did his MSc from CDC, TU, Nepal and recipient of university fellowship award for his outstanding performance in research from Kent State University, USA. Currently, both are pursuing their PhD from Department of Chemistry and Biochemistry and School of Biomedical Sciences, Kent State University, Kent, Ohio 44242, USA.

Their success not only inspires Nepalese but also shows Nepalese are capable, if got the opportunity. Almost all Nepali who had completed their MSc from Tribhuvan University, Nepal had been doing well in foreign. However, there is no reputation of Nepal in science. International journals usually reject if the corresponding author's affiliation is Nepal (personal experience). This is mainly due to unavailability of good equipments, no budget allocation for research and higher study. Receiving chemicals and reagents used in the laboratories are the expensive and slow process. Ministry of “science and technology” is the least preferred for any political parties and politicians. 

And those Nepali scientists who got the international reputation, should be a leader to develop  / install science and technology and research in Nepal, whatever might be our corrupted government thinks. So that all bright young and brilliant Nepali will get chance to show talent, and do something for science.

Influencing Google+ Made me Switching off Facebook

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Although I am beginner of google+, nowadays I am spending more time in it as compared to Facebook. Obviously, some exciting features of Facebook had been luring not only teenagers but also geriatrics. But some limitations such as  option to add as friend only, though all connected people are not friends. Few years ago, I had requested one of my teacher to add as a friend. He knew me. I am confident he knew me, however, he asked to introduce myself. Even though I introduced myself, he doubt as we were friends. Can't we be connected each other in Facebook because we are student and teacher? That's why I have not requested any of my teachers to connect in Facebook yet.

I was asked to introduce before connecting in Facebook but still not connected

Another limitation of Facebook was some status. It might not be appropriate for my relatives connected, but useful for my class fellow. These status couldn't be hidden from each other.I have to restrict selecting one by one. Jokes that I wanted to post, might be laughable for some of my friend of college, which is not necessarily understandable by my friends of school level.

I hope Facebook overcome these limitation within few weeks (or probably, have updated). Otherwise I prefer google+ to Facebook.

नायक राजेश हमाल र सुक्ष्मजीवहरु

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कलाकार / नायक राजेश हमाललाई महानायक बनाएर लेखेका टिपोट को थुप्रो लागिसकेछ । निसन्देह, यो हाँस्य प्रायोजनको लागि मात्र लेखिएको हो । तर, भर्खर-भर्खर Microbiology पढ्न सुरु गर्नेहरुको लागि Bacteria/Virus को characterहरु सम्झिन सजिलो हुन सक्छ ।

1. राजेश दाइलाई त माईक्रोस्कोप नै नचाहिने रहेछ ब्याक्टेरिया हेर्न को लागि ....
2. राजेश दाइ सानो हुँदां Staphylococcus र Streptococcus को गुच्चा खेल्नुहुन्थ्यो रे ।
3. राजेश दाइ सानो हुँदां Escherichia coli र  Vibrio cholera को डण्डीबियो  खेल्नुहुन्थ्यो रे ।  एकदिन, E. coli डण्डीले V. cholera गुलीलाई अलि जोडले हिर्काउनुभएछ, त्यसैले आजसम्म पनि V. cholera बाङ्गोको बाङ्गै छ । 
4. HIV त राजेश दाइसँग डराएर पो रहेछ, CD4 T-cell भित्र लुकि-लुकी बस्ने । 
5. राजेश दाइको लामो कपाल देखेर पो Salmonella typhi पनि peritrichous (झुसे) भएको रहेछ ।
6. २०५१ सालमा नेपालमा ठुलो खडेरी परेको थियो, किन भनेर बुझ्दै जांदा त राजेश दाइले Agaricus biospora (mushroom) को छाता बनाएर ओढ्नु भएको रहेछ ।
7. राजेश दाइले एउटा भुस्याहा कुकुरलाई गोली हान्नु भएछ, गोली लाग्यो, घाऊ-रगत देखिएन, तर पानी देखी डराउने मात्र भएछ, १४ दिनपछी बल्ल कुकुर मरेछ । यसपल्ट त राजेश दाइपनि अचम्म पर्नुभएछ । (Bullet shaped Rhabdovirus).
8. राजेश दाइको 'देउता' चलचित्र हेरेपछि Proteus त एकै ठाउँमा बस्न नसक्ने चकचके भएछ । (Swarming motility of Proteus spp.)

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बिष्णु प्र. मरासिनी

Lumbini, Nepal, The Birth Place of Buddha (Siddhartha Gautam)

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2,500 ago, the powerful and influencing Nepal had given birth to Lord Buddha (623 BC) who lead the pathway of peace and civilization for humankind. Currently, this place is located in the Rupandehi district. But in modern days, Nepal ???........  Again, Nepal should be a leading country to the destination for peace and tranquillity.

Use light to show pathway for peace

Origin of peace

Art and peaceful life

Elysium in the mortal world

After following Budhha, Asoka became more happier and greater than as a Emperor

Please, stop violence, share love and knowledge, save the Earth

 Reference: World Heritage List

Pathogenesis of Arthritis

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Arthritis is the painful disorder of joints, a leading cause for the disability in geriatrics. Osteoarthritis (OA), rheumatoid arthritis (RA), gout, lupus etc. are the common types of arthritis. OA is a disease aquired by 'wear and tear', and injury leading to cartilage degradation. RA is chronic inflammatory disorder attacking mainly the joints. Gout develops due to monosodium urate (MSU) crystal deposition in synovial fluid.

Pathogenesis of arthritis is mainly due to the following reasons. The activation of immune cells because of cross reactivity with bacteria, virus, pollen grains etc., which share common epitope with synovium or defects in genes like HLA-DRB1*0401, single nucleotide polymorphism (PTPN22, STAT4, CDK6, etc.). Complement complex, C5b678(9)n are deposited on synovial lining and opsonize it. These immune cells release pro-inflammatory cytokines, which intitaites  proliferation of fibroblast and osteoclast, and ultimately demineralize and destroy the bone matrix. Agonist of RANK, TLR2, etc. trigger the activation of NF-kB, which ultimately produces matrix metalloproteinase, nitric oxide and other bone degenarating enzymes. Due to obesity, axial  force as well as varus malalignment increases, hence cartilage begin to erode. Uric acid (purine) is overproduced due to some hyperactive enzymes or overturn of nucleic acid rich dietary source, and renal failure (not removing of urate).

Joint damage and pain due to arthritis can be reduced using ice, joint replacement, physiotherapy, hyaluronic acid administration, avoiding purine rich diet, administration of drugs such as methotrexate, etanercept, infliximab, rituximab, tocilizumab, Ibuprofen, corticosteroids, colchicine, diclofenac,  allopurinol, etc.
(To be Continue.....) (Update: View part II)
References

1. Porth, C.M, and Matfin, G. Pathophysiology, concept of altered health states, 8th edition, Lippincott Willian and Wilkins Publisher (2009)
2. Firestein, G.S. Evolving concepts of rheumatoid arthritis. Nature 423, 356-361(2003)
3. El-Gabalawy H. S. et al.,  Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population, Genes and Immunity, Doi :10.1038/gene.2011.30(2011)
4. Loughlin, J. Osteoarthritis: All types of trouble-defining OA in the genomic era. Nature Reviews Rheumatology 7, 200-201(2011)

Epidemics of Diarrhea due to Escherichia coli (Shiga toxin producing enterohemorrhagic) in Europe

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Recently, enterohemorrhagic Escherichia coli (EHEC) strain has infected over 3,500 and kills over 40 people in the Europe and most of them are German [1]. Initially, it was blamed to salad and vegetables and the farmers for the cause of transmission, as concluded by case-control study. But the causative bacterial strain, EHEC O104:H4 has not been found in any of these salad and vegetables samples. Then authorities realize farmers were not culpable. Then they withdraw the blame with apology and announce the compensation for farmers. Now suspecting on bean, sprout, and agricultural practice [2].

EHEC O104:H4 is a type of E. coli classified on the basis of somatic O-antigen (over 170 different type: 1-170), and flagellar H-antigen (over 50 different types: 1-50). In E. coli, there are different chemical structure and functional group comprising lipopolysaccharide of plasma membrane (O-antigen), polysaccharide of  capsule (K-antigen) and flagella (H-antigen). Combining of these different antigens there could be thousands of different types of E. coli. The infective EHEC O104:H4 is new to Europe but this strain was reported from Korea in 2006 [3]. Does this means this strain is shipped from Korea? Certainly not, or needs exigent research.

Every organism has the tendency to adapt the environment with necessary genotype reshuffle or addition, and phenotypic variation, suitable to survive, as Darwinism. Bacterial strains also, always tend to increase virulence and pathogenicity by adapted gene transfer and mutation. In latent type of infection, plasmid and/or gene transferred from virulent strain to non-virulent may get proliferated for several months without symptom and unknown to health professional. This may be the one of the possible reason for outbreak in Europe, which is still under research to find the source of infection. So, the organism whose reservoir is the environment, they proliferated when the environmental condition becomes optimum, as said by Rita Colwell [6].

Vibrio, Escherichia has the environmental reservoir unlike smallpox and polio virus. So they are always prone to infect mammal once environmental condition become favourable. E. coli is even more dangerous as it is opportunistic pathogen and can acquire antibiotic resistance as well as virulence.

In my study (in NAST), some strains of E. coli were found to be resistant against all commonly used antibiotics (courtesy: Nabaraj Dahal, Pankaj Baral, and Sanjiv Neupane). This shows it is the dreadful strain having most flexibility in genetic variation among bacterial kingdom. However, the innovation and more research on antibiotics may enervates its massive proliferation.

Multi-drug resistant E. coli reconfirmed on M-endo agar.

Antibiotics sensitive E. coli (ATCC 25922) reconfirmed on M-endo agar.

Even in the Europe, the bacterial strain can invade people where living standard is high as well as good sanitation, well managed health system. Also, Nepal had faced problem of diarrhoeal epidemics and hundreds of people died in remote area, two years ago. But it was different scenario, poor people were lack of medicine and ORS.
Few months ago, an unprecedented outbreak of cholera in Haiti was the reason to blame Nepalese peacekeeping soldier. But neither stool nor rectal swab nor antibody test of these soldiers showed positive result of V. cholera (or was not investigated). Even no one could be verified as carrier. And probably, the sample of drinking water, seawater and sewage from different source was not analysed properly to make a conclusion. Only the co-incidence was the bacterial strain found there resembled with the South Asian strain, which is not only confined in Nepal but also other South Asian countries like Bangladesh, India, Pakistan etc.

References:

1. European Centre for Disease Prevention and Control,  Stockholm, Sweden, 22 June 2011, 11:00
2. Editorials, 16 June, 2011, Nature, Vol. 474, 251
3. Woo Kyun Bae, et al., Jun 2006, Yonsei Medical Journal, Vol. 47(3), 437-439
4. Marian Turner,  9 June, 2011, Nature, Vol. 474, 137
5. Kai Kupferschmidt, 10 June 2011, Science, Vol. 332, 1249-1250
6. Martin Enserink, 5 November 2010, Science, Vol. 330, 738-739