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Alexion’s Soliris® (eculizumab) Receives Orphan Drug Designation for the Treatment of Neuromyelitis Optica (NMO)

Structure of eculizumab. Eculizumab was engineered to reduce immunogenicity and eliminate effector function. Human IgG2 and IgG4 heavy-chain sequences were combined to form a hybrid constant region that is unable to bind Fc receptors or to activate the complement cascade. Eculizumab exhibits high affinity for human C5, effectively blocking its cleavage and downstream proinflammatory and cell lytic properties. Reprinted from Rother et al with permission.  

Alexion's Soliris® (eculizumab) Receives Orphan Drug Designation for the ...

Fort Mills Times
In a Phase 2 study presented at the 2012 annual meeting of the American Neurological Association (ANA), Soliris treatment was associated with a significant reduction in the frequency of relapses (recurring attacks) in patients with severe, relapsing ...

http://www.fortmilltimes.com/2013/06/27/2789656/alexions-soliris-eculizumab-receives.html


Eculizumab (INN and USAN; trade name Soliris) is a humanized monoclonal antibody that is a first-in-class terminal complement inhibitor and the first therapy approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare, progressive, and sometimes life-threatening disease characterized by excessive destruction of red blood cells (hemolysis). It costs £400,000 (US$600,000) per year per patient

Eculizumab also is the first agent approved for the treatment of atypical hemolytic uremic syndrome (aHUS), an ultra-rare genetic disease that causes abnormal blood clots to form in small blood vessels throughout the body, leading to kidney failure, damage to other vital organs and premature death.

In clinical trials in patients with PNH, eculizumab was associated with reductions in chronic hemolysis, thromboembolic events, and transfusion requirements, as well as improvements in PNH symptoms, quality of life, and survival.Clinical trials in patients with aHUS demonstrated inhibition of thrombotic microangiopathy (TMA),the formation of blood clots in small blood vessels throughout the body, including normalization of platelets and lactate dehydrogenase (LDH), as well as maintenance or improvement in renal function.

Eculizumab was discovered and developed by Alexion Pharmaceuticals and is manufactured by Alexion. It was approved by the United States Food and Drug Administration (FDA) on March 16, 2007 for the treatment of PNH, and on September 23, 2011 for the treatment of aHUS. It was approved by the European Medicines Agency for the treatment of PNH on June 20, 2007, and on November 24, 2011 for the treatment of aHUS. Eculizumab is currently being investigated as a potential treatment for other severe, ultra-rare disorders.

Celgene buys MophoSys for myeloma antibody development

Celgene buys MophoSys for myeloma antibody development
German biopharmaceutical company MorphoSys will jointly develop an antibody for the treatment of multiple myeloma (MM) and leukaemia with Celgene Corporation. 

http://www.pharmaceutical-technology.com/news/newscelegene-buys-mophosys-for-myeloma-antibody-development?WT.mc_id=DN_News

Novartis' Omalizumab Meets Phase III Endpoints

Novartis' Omalizumab Meets Phase II...

Novartis reports new Phase III data showing omalizumab significantly...



http://www.pharmalive.com/novartis-omalizumab-meets-phase-iii-endpoints

Structures of resistance-breaking derivatives of established antibiotic classes. Selected compounds are depicted that were recently launched or are currently in development. Ceftobiprole has increased affinity for PBP2a, a member of the target family of penicillin-binding proteins not affected by marketed β-lactams. Tigecycline, iclaprim, telithromycin, and telavancin make contacts to additional binding sites on their established targets or address additional targets. Structural elements responsible for the novel target interactions are marked bold. MCB-3681, TD-1792, and CBR-2092 are hybrid molecules, in which two pharmacophors from different antibiotic classes are attached by linkers. Linkers are marked bold

All antibiotics that have been successfully employed for decades as monotherapeutics in the treatment of bacterial infections rely on mechanisms of bacterial growth inhibition which are by far more complex than inhibition of a single enzyme. Such successful antibiotics have in common that they address several targets in parallel and/or that their targets are encoded by multiple genes. Such multiplicity of targets and of target genes has the advantage that the emergence of spontaneous target-related resistance is a comparatively slow process. Recently registered antibiotics and novel antibiotics in development are discussed in the light of this promising concept of antibacterial polypharmacology.

How many modes of action should an antibiotic have?

• Heike Brötz-Oesterhelt 
• Nina A Brunner 

• AiCuris GmbH & Co.KG, Friedrich-Ebert Strasse 475, Building 302, D-42117 Wuppertal, Germany

Available online 30 July 2008

• http://dx.doi.org/10.1016/j.coph.2008.06.008,

http://www.sciencedirect.com/science/article/pii/S1471489208000799

Preventing Dangerous Liaisons

A new peptidomimetic inhibits prostate cancer’s growth by preventing the androgen receptor from binding to its cofactor
Read more

http://www.chemistryviews.org/details/news/4884471/Preventing_Dangerous_Liaisons.html

Gut Feeling for Obesity Treatment

Gut Feeling for Obesity Treatment

Newly synthesized benzimidazole-type compounds work directly in the gut rather than circulating in the blood to lower triglycerides
Read more

http://www.chemistryviews.org/details/news/4907951/Gut_Feeling_for_Obesity_Treatment.html

Silibinin (INN), also known as silybin, is the major active constituent of silymarin, a standardized extract of the milk thistle seeds containing mixture of flavonolignans consisting of among others of silibinin, isosilibinin, silicristin, and silidianin

Silibinin (INN), also known as silybin, is the major active constituent of silymarin, a standardized extract of the milk thistle seeds containing mixture of flavonolignans consisting of among others of silibinin, isosilibinin, silicristin, and silidianin. Silibinin itself is mixture of two diastereomers silibinin A and silybinin B in approximately equimolar ratio. Both in vitro and animal research suggest that silibinin has hepatoprotective (antihepatotoxic) properties that protect liver cells against toxins.^[1][2] Silibinin has also demonstrated in vitro anti-cancer effects against human prostate adenocarcinoma cells, estrogen-dependent and -independent human breast carcinoma cells, human ectocervical carcinoma cells, human colon cancer cells, and both small and nonsmall human lung carcinoma cells.^[3][4][5][6]
Chemically modified silibinin, silibinin dihydrogen disuccinate disodium (trade name Legalon SIL) a solution for injection, is currently being tested as a treatment of severe intoxications with hepatotoxic substances, such as death cap (Amanita phalloides) poisoning.^[7] There is also clinical evidence for the use of silibinin as a supportive element in alcoholic and Child grade ‘A’ liver cirrhosis.^[8]

 FROM SILYBUM MARIANUM (L.) GAERTN.
A NEW NATURAL PREVENTIVE TARGETED AT THE LIVER
The liver, due to the vital role it plays in metabolism, is particularly exposed to the harmful action of endogenous and exogenous toxic substances. In fact, many potentially harmful molecules (alcohol, drugs, hormones, etc.) are metabolized by the liver and transformed into more hydro-soluble derivatives for subsequent biliary extraction and removal from the body. This detoxication process is achieved by a variety of enzymes (oxidizing, reducing, hydrolyzing or conjugating) located in the hepatic microsomes, part of the smooth endoplasmic reticulum of the liver cell. For this reason the upkeep of the integrity of the liver cell is necessary for the safeguarding of health. Several biochemical reactions involve as starters or intermediates various free radical species which constitute a continuous risk factor for the integrity of the hepatocytes.Therefore, any prevention aimed at reducing potential damage to the liver and any substances contributing to its integrity are certainly of interest. Derivatives of the traditionally used European plant Silybum marianum (L.) Gaertn. (Asteraceae) occupy an eminent position in liver protection. The name Silybum derives from "sillybon" (tuft, pendant), an ancient Greek word used by Dioscorides (I century A.D.) to indicate a thistle with white spotted leaves. An old legend tells that these white marks and stripes on the leaves represent the drops of Mary's milk fallen from her breast while she was breastfeeding Jesus during their escape to Egypt.² Since ancient times S. marianum has been known and used to be recommended as an emetic. During the Middle Ages the plant was probably cultivated in monasteries and used for medicinal purposes: the roots, herb and leaves were recommended for swelling and erysipelas (St. Hildegard from Bingen, 1098-1179) or for the treatment of liver complaints (Lonicerus, John Gerard, Pietro Andrea Mattioli, XVI-XVII centuries). From 1755 onwards, the specific use of S. marianum fruit for the treatment of liver disease, disorders of the bile duct and spleen was documented. At present, the standardized extract (silymarin) obtained from the fruit of S. marianum and containing as main constituents silybin, silydianin and silychristin (Fig.1), is widely used in European medicine in the treatment of liver disease. The main constituent silybin has been subjected to several biochemical and pharmacological studies which have demonstrated its interesting properties but also its poor bioavailability. Complexation with soy phosphatidylcholine gives rise to the lipophilic complex (US Patent 4, 764, 508) which substantially improves the bioavailibility of silybin. This results in a marked preventive action as observed in several models of liver intoxication including those with a strong involvement of oxidative stress. In this way, the silybin-phosphatidylcholine complex SILIPHOS®, containing 33% of silybin, endowed with antioxidant activity and, simultaneously, able to prevent cellular derangement by stabilizing the cell membranes and restoring the normal ultrastructure of the hepatocytes, plays a key role in the prevention of liver damage.http://www.swansonvitamins.com/health-library/products/siliphos.html

1. Al-Anati L, Essid E, Reinehr R, Petzinger E (2009). "Silibinin protects OTA-mediated TNF-alpha release from perfused rat livers and isolated rat Kupffer cells". Molecular Nutrition & Food Research 53 (4): 460–6. doi:10.1002/mnfr.200800110. PMID 19156713.
2. Jayaraj R, Deb U, Bhaskar AS, Prasad GB, Rao PV (2007). "Hepatoprotective efficacy of certain flavonoids against microcystin induced toxicity in mice". Environmental Toxicology 22 (5): 472–9. doi:10.1002/tox.20283. PMID 17696131.
3. Mokhtari MJ, Motamed N, Shokrgozar MA (2008). "Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line". Cell Biology International 32 (8): 888–92. doi:10.1016/j.cellbi.2008.03.019. PMID 18538589.
4. Bhatia N, Zhao J, Wolf DM, Agarwal R (1999). "Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin". Cancer Letters 147 (1–2): 77–84. doi:10.1016/S0304-3835(99)00276-1. PMID 10660092.
5. Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS (2007). "Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer". Journal of Surgical Research 143 (1): 58–65. doi:10.1016/j.jss.2007.03.080. PMID 17950073.
6. Sharma G, Singh RP, Chan DC, Agarwal R (2003). "Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells". Anticancer Research 23 (3B): 2649–55. PMID 12894553.
7. Mitchell, T (2009). "Intravenous Milk thistle (silibinin-legalon) for hepatic failure induced by amatoxin/Amanita mushroom poisoning". (Clinical study).
8. Saller R, Brignoli R, Melzer J, Meier R (2008). "An updated systematic review with meta-analysis for the clinical evidence of silymarin". Forschende Komplementärmedizin (2006) 15 (1): 9–20. doi:10.1159/000113648. PMID 18334810. Retrieved 2010-12-14.

A combination of the myxoma virus and the immune suppressant rapamycin can kill glioblastoma multiforme, the most common and deadliest malignant brain tumor

 read all at

http://www.dddmag.com/news/2013/06/virotherapy-rapamycin-combo-kills-brain-tumors

rapamycin, sirolimus

.Artificial sweetener a potential treatment for Parkinson’s disease.

Mannitol, a sugar alcohol produced by fungi, bacteria, and algae, is a common component of sugar-free gum and candy. The sweetener is also used in the medical field — it’s approved by the FDA as a diuretic to flush out excess fluids and used during surgery as a substance that opens the blood/brain barrier to ease the passage of other drugs.

Now Profs. Ehud Gazit and Daniel Segal of Tel Aviv University‘s Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience, along with their colleague Dr. Ronit Shaltiel-Karyo and PhD candidate Moran Frenkel-Pinter, have found that mannitol also prevents clumps of the protein α-synuclein from forming in the brain — a process that is characteristic of Parkinson’s disease.

Read more at

http://scienceblog.com/63913/artificial-sweetener-a-potential-treatment-for-parkinsons-disease/

STARTING MATERIALS IN API MANUFACTURING, ROLES, REG ASPECTS :: DRUG SCALEUP AND MANUFACTURING INTERNATIONAL

STARTING MATERIALS IN API MANUFACTURING, ROLES, REG ASPECTS :: DRUG SCALEUP AND MANUFACTURING INTERNATIONAL

Ambrx partners with Zhejiang for breast cancer antibody drug conjugate development

Ambrx has partnered with Zhejiang Medicine for the development and commercialization of ARX788, its antibody drug conjugate (ADC) for breast cancer... Targeting Her2-positive breast cancer, ARX788 is developed by the clinical stage biopharmaceutical company Ambrx as site-specific ADC.

http://contractresearch.pharmaceutical-business-review.com/news/ambrx-partners-with-zhejiang-for-breast-cancer-antibody-drug-conjugate-development-170613

MEDICINE IN ANCIENT EGYPT

 


Historically, many Egyptologists focused primarily on the very visible aspects of ancient Egyptian society, such as the pyramids, much to the bain of those interested in more than just monumental architecture. From the beginning of the scholarly study of Egypt's past there have been few scholars who recognized the importance of the process of disease and health on a population. With the turn of the century, new archaeological discoveries, increased knowledge of Egyptian language and writing, and the advent of more sophisticated medical techniques, new life was breathed into the study of disease and health in the ancient Nile Valley. It was this period that saw the academic study of Egyptian disease segregated into three distinct categories.
The first is the study of medical Papyri. Early on it was recognized that the textual material of the Dynastic Period pertaining to the recognition and treatment of disease was extremely important for understanding both the state of health as well as the concept of disease in ancient Egypt. The second is the study of the artistic representation of disease in the Nile Valley. The Egyptian's predilection to portrayl life in a relatively realistic manner offers an excellent opportunity for the study of disease. The third, and perhaps most obvious, is the study of human remains, both skeletal and soft tissue, of ancient Egyptians. With the advent of increasingly sophisticated medical techniques at the beginning of the 20th century, as well as those complex medical techniques in use today, the analysis of Egypt's veritable wealth of human remains provided a tremendous boost to the study of the state of disease and health in the ancient Nile Valley.


Medical Papyri 


The Edwin Smith Papyrus 


The Edwin Smith Surgical Papyrus is, without a doubt, one if the most important documents pertaining to medicine in the ancient Nile Valley. Placed on sale by Mustafa Agha in 1862, the papyrus was purchased by Edwin Smith. An American residing in Cairo, Smith has been described as an adventurer, a money lender, and a dealer of antiquities.(Dawson and Uphill: 1972). Smith has also been reputed as advising upon, and even practicing, the forgery of antiquities.(Nunn 1996:26) Whatever his personal composition, it is to his credit that he immediately recognized the text for what it was and later carried out a tentative translation. Upon his death in 1906, his daughter donated the papyrus in its entirety to the New York Historical Society. The papyrus now resides in the collections of the New York Academy of Sciences.
In 1930, James Henry Breasted, director of the Oriental Institute at the University of Chicago, published the papyri with facsimile, transcription, English translation, commentary, and introduction. The volume was accompanied by medical notes prepared by Dr. Arno B. Luckhardt. To date, the Breasted translation is the only one if its kind.
The Edwin Smith papyrus is second in length only to the Ebers papyrus, comprising seventeen pages (377 lines) on the recto and five pages (92 lines) on the verso. Both the recto and the verso are written with the same hand in a style of Middle Egyptian dating.


The Ebers Papyrus 


Like the Edwin Smith Papyrus, the Ebers Papyrus was purchased in Luxor by Edwin Smith in 1862. It is unclear from whom the papyrus was purchased, but it was said to have been found between the legs of a mummy in the Assassif district of the Theben necropolis.
The papyrus remained in the collection of Edwin Smith until at least 1869 when there appeared, in the catalog of an antiquities dealer, and advertisement for "a large medical papyrus in the possession of Edwin Smith, an American farmer of Luxor."(Breasted 1930) The Papyrus was purchased in 1872 by the Egyptologist George Ebers, for who it is named. In 1875, Ebers published a facsimile with an English-Latin vocabulary and introduction.
The Ebers Papyrus comprises 110 pages, and is by far the most lengthy of the medical papyri. It is dated by a passage on the verso to the 9th year of the reign of Amenhotep I (c. 1534 B.C.E.), a date which is close to the extant copy of the Edwin Smith Papyrus. However, one portion of the papyrus suggests a much earlier origin. Paragraph 856a states that : "the book of driving wekhedu from all the limbs of a man was found in writings under the two feet of Anubis in Letopolis and was brought to the majesty of the king of Upper and Lower Egypt Den."(Nunn 1996: 31) The reference to the Lower Egyptian Den is a historic anachronism which suggesting an origin closer to the First Dynasty (c. 3000 B.C.E.)
Unlike the Edwin Smith Papyrus, the Ebers Papyrus consists of a collection of a myriad of different medical texts in a rather haphazard order, a fact which explains the presence of the above mentioned excerpt. The structure of the papyrus is organized by paragraph, each of which are arranged into blocks addressing specific medical ailments.
Paragraphs 1-3 contain magical spells designed to protect from supernatural intervention on diagnosis and treatment. They are immediately followed by a large section on diseases of the stomach (khet), with a concentration on intestinal parasites in paragraphs 50-85.(Bryan 1930:50) Skin diseases, with the remedies prescribed placed in the three categories of irritative, exfoliative, and ulcerative, are featured in paragraphs 90-95 and 104-118. Diseases of the anus, included in a section of the digestive section, are covered in paragraphs 132-164.(Ibid. 50) Up to paragraph 187, the papyrus follows a relatively standardized format of listing prescriptions which are to relieve medical ailments. However, the diseases themselves are often more difficult to translate. Sometimes they take the form of recognizable symptoms such as an obstruction, but often may be a specific disease term such as wekhedu or aaa, the meaning of both of which remain quite obscure.

Paragraphs 188-207 comprise "the book of the stomach," and show a marked change in style to something which is closer to the Edwin Smith Papyrus.(Ibid.: 32) Only paragraph 188 has a title, though all of the paragraphs include the phrase: "if you examine a man with a…," a characteristic which denotes its similarity to the Edwin Smith Papyrus. From this point, a declaration of the diagnosis, but no prognosis. After paragraph 207, the text reverts to its original style, with a short treatise on the heart (Paragraphs 208-241).
Paragraphs 242-247 contains remedies which are reputed to have been made and used personally by various gods. Only in paragraph 247, contained within the above mentioned section and relating to Isis' creation of a remedy for an illness in Ra's head, is a specific diagnosis mentioned. (Bryan 1930:45)
The following section continues with diseases of the head, but without reference to use of remedies by the gods. Paragraph 250 continues a famous passage concerning the treatment of migraines. The sequence is interrupted in paragraph 251 with the focus placed on a drug rather than an illness. Most likely an extract from pharmacopoeia, the paragraph begins: "Knowledge of what is made from degem (most likely a ricinous plant yielding a form of castor oil), as something found in ancient writings and as something useful to man."(Nunn 1996: 33)
Paragraphs 261-283 are concerned with the regular flow of urine and are followed by remedies "to cause the heart to receive bread."(Bryan 1930:80). Paragraphs 305-335 contain remedies for various forms of coughs as well as the genew disease.
The remainder of the text goes on to discuss medical conditions concerning hair (paragraphs 437-476), traumatic injuries such as burns and flesh wounds (paragraphs 482-529), and diseases of the extremities such as toes, fingers, and legs. Paragraphs 627-696 are concerned with the relaxation or strengthening of the metu. The exact meaning of metu is confusing and could be alternatively translated as either mean hollow vessels or muscles tissue.(Ibid.:52) The papyrus continues by featuring diseases of the tongue (paragraphs 697-704), dermatological conditions (paragraphs 708-721), dental conditions (paragraphs 739-750), diseases of the ear, nose, and throat (paragraphs 761-781), and gynecological conditions (paragraphs 783-839)


Kahun Gynecological Papyrus 

The Kahun Papyrus was discovered by Flinders Petrie in April of 1889 at the Fayum site of Lahun. The town itself flourished during the Middle Kingdom, principally under the reign of Amenenhat II and his immediate successor. The papyrus is dated to this period by a note on the recto which states the date as being the 29th year of the reign of Amenenhat III (c. 1825 B.C.E.). The text was published in facsimile, with hieroglyphic transcription and translation into English, by Griffith in 1898, and is now housed in the University College London.
The gynecological text can be divided into thirty-four paragraphs, of which the first seventeen have a common format.(Nunn 1996: 34) The first seventeen start with a title and are followed by a brief description of the symptoms, usually, though not always, having to do with the reproductive organs.
The second section begins on the third page, and comprises eight paragraphs which, because of both the state of the extant copy and the language, are almost unintelligible. Despite this, there are several paragraphs that have a sufficiently clear level of language as well as being intact which can be understood. Paragraph 19 is concerned with the recognition of who will give birth; paragraph 20 is concerned with the fumigation procedure which causes conception to occur; and paragraphs 20-22 are concerned with contraception. Among those materials prescribed for contraception are crocodile dung, 45ml of honey, and sour milk.(Ibid:35)
The third section (paragraphs 26-32) is concerned with the testing for pregnancy. Other methods include the placing of an onion bulb deep in the patients flesh, with the positive outcome being determined by the odor appearing to the patients nose.
The fourth and final section contains two paragraphs which do not fall into any of the previous categories. The first prescribes treatment for toothaches during pregnancy. The second describes what appears to be a fistula between bladder and vagina with incontinence of urine "in an irksome place."(Ibid. 35)


The Investigation of Disease Patterns Through Human Remains and Artistic Representations 


Parasitic Diseases 


Schistosomiasis (bilharziasis) 


Of the three main species of the platyhelminth worm Schistosoma, the most important for Egypt are S. mansoni and S. haematobium. There is a complex life cycle alternating between two hosts, humans and the fresh water snail of the genus Bulinus. The infection is caught by humans who come into contact with the free swimming worm which the snail releases in the water. The worm penetrates the intact skin and enters the veins of the human host. The main symptom of the presence of the parasite is haematuria which results in serious anemia, loss of appetite, urinary infection, and loss of resistance to other diseases. There may also be interference with liver functions.
One of the finest archaeological examples for the existence of schistosomiasis in ancient Egypt was the discovery of calcified ova in the unembalmed 21st Dynasty mummy of Nakht. Upon medical examination, the mummy not only exhibited a preserved tapeworm, but also ova of the Schistosoma haematobium and displayed changes in the liver resulting from a schistosomal infection.(Millat et al. 1980:79)


Bacterial and Viral Infections 


Tuberculosis (Mycobacterium tuberculosis) 


Ruffer (1910) reported the presence of tuberculosis of the spine in Nesparehan, a priest of Amun of the 21st Dynasty. This shows the typical features of Pott's disease with collapse of thoracic vertebra, producing the angular kyphosis (hump-back). A well known complication of Pott's disease is the tuberculous suppuration moving downward under the psoas major muscle, towards the right iliac fossa, forming a very large psoas abscess.(Nunn 1996:64)
Ruffer's report has remained the best authenticated case of spinal tuberculosis from ancient Egypt. All known possible cases, ranging from the Predynastic to 21st Dynasty were reviewed by Morse, Brockwell, and Ucko (1964) as well as by Buikstra, Baker, and Cook.(1993) These included Predynastic specimens collected at Naqada by Petrie and Quibell in 1895 as well as nine Nubian Specimens from the Royal College of Surgeons of England. Both reviewers were in agreement that there was very little doubt that tuberculosis was the cause of pathology in most, but not all, cases. In some cases, it was not possible to exclude compression fractures, osteomyelitis, or bone cysts as causes of death.
The numerous artistic representation of hump-backed individuals are provocative but not conclusive. The three earliest examples are undoubtedly of Predynastic origin. The first is a ceramic figurine reported to have been found by Bedu in the Aswan district. It represents an emaciated human with angular kyphosis of the thoracic spine crouching in a clay vessel.(Schrumph-Pierron 1933) The second possible Predynastic representation with spinal deformity indicative of tuberculosis is a small standing ivory likeness of a human with arms down at the sides of the body bent at the elbows. The head is modeled with facial features carefully indicated. The figure is shown with a protrusion of the back and on the chest.(Morse 1967: 261) The last Predynastic example is a wooden statue contained within the Brussels Museum. Described as a bearded male with intricate facial features, the figure has a large rounded hunch-back and an angular projection of the sternum.(Jonckheere 1948: 25)
As well, there are several historic Egyptian representations which indicate the possibility of tuberculosis deformity. One of the most suggestive, located in and Old Kingdom 4th Dynasty tomb, is of a bas relief serving girl who exhibits localized angular kyphosis. A second provocative example has its origin in the Middle Kingdom. A tomb painting at Beni Hasan, the representation shows a gardener with a localized angular deformity of the cervical-thoracic spine.(Morse 1967: 263)


Poliomyelitis 


A viral infection of the anterior horn cells of the spinal chord, the presence of poliomyelitis can only be detected in those who survive its acute stage. Mitchell (Sandison 1980:32) noted the shortening of the left leg, which he interpreted as poliomyelitis, in the an early Egyptian mummy from Deshasheh. The club foot of the Pharaoh Siptah as well as deformities in the 12th Dynasty mummy of Khnumu-Nekht are probably the most attributable cases of poliomyelitis.
An 18th or 19th Dynasty funerary staele shows the doorkeeper Roma with a grossly wasted and shortened leg accompanied by an equinus deformity of the foot. The exact nature of this deformity, however, is debated in the medical community. Some favor the view that this is a case of poliomyelitis contracted in childhood before the completion of skeletal growth. The equinus deformity, then, would be a compensation allowing Roma to walk on the shortened leg. Alternatively, the deformity could be the result of a specific variety of club foot with a secondary wasting and shortening of the leg.(Nunn 1996: 77)


Deformities 


Dwarfism 


Dasen (1993) lists 207 known representations of dwarfism. Of the types described, the majority are achondroplastic, a form resulting in a head and trunk of normal size with shortened limbs. The statue of Seneb is perhaps the most classic example. A tomb statue of the dwarf Seneb and his family, all of normal size, goes a long way to indicate that dwarfs were accepted members in Egyptian society. Other examples called attention to by Ruffer (1911) include the 5th Dynasty statuette of Chnoum-hotep from Saqqara, a Predynastic drawing of the "dwarf Zer" from Abydos, and a 5th Dynasty drawing of a dwarf from the tomb of Deshasheh.
Skeletal evidence, while not supporting the social status of dwarfs in Egyptian society, does corroborate the presence of the deformity. Jones (Brothwell 1967:432) described a fragmentary Predynastic skeleton from the cemetery at Badari with a normal shaped cranium both in size in shape. In contrast to this, however, the radii and ulna are short and robust, a characteristic of achondroplasia. A second case outlined by Jones (Ibid.:432) consisted of a Predynastic femur and tibia, both with typical short shafts and relatively large articular ends.


References 


Breasted, J.H. - The Edwin Smith Surgical Papyrus (University of Chicago Press: University of Chicago, 1930)
Brothwell, D. - "Major Congenital Anomalies of the Skeleton," in Diseases in Antiquity: A Survey of Disease, Injuries, and Surgery in Early Populations (eds.) A.T. Sandison and D. Brothwell (Charles C. Thomas: Springfield, 1967)
Bryan, P.W.  - The Papyrus Ebers (Geoffrey Bles: London, 1930)
Buikstra, J.E.; Baker, B.J.; Cook, D.C.- "What Disease Plagues the Ancient Egyptians? A Century of Controversy Considered," In Biological Anthropology and the Study of Ancient Egypt (eds.) W,V. Davies and R. Walter (British Museum Press: London, 1993)
Dasen, V. - Dwarfs in Ancient Egypt and Greece (Clarendon Press: Oxford, 1993)
Dawson, W.R. and E.P. Uphill - Who Was Who in Egyptology (Egyptian Exploration Society: London, 1993)
Jonckheere, F. - "Le Bossu des Mussées Royaux D'Art et D'Histoire de Bruxelles," Chronique D'Égypt (45) 25, 1958.
Millet, N.; Hart, G.; Reyman, T.; Zimerman, A.; Lewein, P. - "ROM I: Mummification for the Common People," in Mummies, Disease, and Ancient Cultures (eds.) Aiden and Eve Cockburn (Cambridge University Press: Cambridge, 1980)
Morse, D. - "Tuberculosis," in Diseases in Antiquity: A Survey of Diseases, Injuries, and Surgery in Early Populations (eds.) A.T. Sandison and D. Brothwell (Charles Thomas: Springfield, 1967)
Morse, D.; Brothwell, D.; Ucko, P.J.  - "Tuberculosis in Ancient Egypt," in American Review of Respiratory Diseases (90), 1964)
Nunn, J.F. - Ancient Egyptian Medicine (University of Oklahoma Press: Norman, 1996)
Ruffer, M.A. -"Potts'che Krankheit an Einer Ägyptischer Mumie aus der Zeiy der 21 Dynastie," in Zur Historischen Biologie der Krankheiserreger (3), 1910 "On Dwarfs and Other Deformed Persons," Bulletin de Societé D'Archéologie D'Alexandrie (13)1, 1911
Sandison, A.T. - "Diseases in Ancient Egypt," in Mummies, Disease, and Ancient Cultures (eds.) Aiden and Eve Cockburn (Cambridge University Press: Cambridge, 1980)
Schrumph-Pierron, B. - "La Mal de Pott en Égypt 4000 Ans Avant Notre Ére," Aesculpe (23)1933

Chemical Nanoengineering: Designing Drugs Controlled by Light

Researchers at IRB Barcelona and IBEC design the first peptides regulated by light to modulate biological processes. (Credit: Copyright Laura Nevola)





The scientific cooperation between chemists, biotechnologists and physicists from various Catalan institutes, headed by Pau Gorostiza, from the Institute for Bioengineering of Catalonia (IBEC), and Ernest Giralt, from the Institute for Research in Biomedicine (IRB Barcelona), has led to a breakthrough that will favor the development of light-regulated therapeutic molecules.

read all at
 http://www.sciencedaily.com/releases/2013/06/130618101516.htm?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+sciencedaily%2Fmatter_energy%2Forganic_
chemistry+%28ScienceDaily%3A+Matter+%26+Energy+News+--+Organic+Chemistry%29

HANDBOOK OF MEDICINAL HERBS-by DOCSTOC

Handbook of Medicinal Herbs (PDF)

INDA

Investigational new drug application from Gaurav Kr

Incyte Drug Jakafi ® (ruxolitinib) Improved Overall Survival in Phase III Trial of Patients with Myelofibrosis

ruxolitinib Incyte Drug Jakafi®ruxolitinib Improved Overall Survival in Phase ... Incyte Drug Jakafi®ruxolitinib Improved Overall Survival in Phase III Trial of Patients with Myel. by Business Wirevia The Motley Fool Jun 16th 2013 220AM ... http://www.dailyfinance.com/2013/06/16/incyte-drug-jakafi-ruxolitinib-improved-overall-su/ Ruxolitinib (trade names Jakafi and Jakavi, by Incyte Pharmaceuticals and Novartis) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of bone marrow cancer. It is also being investigated for the treatment of other types of cancer (such as lymphomas and pancreatic cancer), for polycythemia vera, and for plaque psoriasis. The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size, relieving debilitating symptoms, and improving overall survival

ABILIFY® Granted Additional Approval as Adjunctive Therapy for the Treatment of Depression in Japan

ABILIFY® Granted Additional Approval as Adjunctive Therapy for the Treatment of Depression in Japan

Otsuka Pharmaceutical Co., Ltd. today obtained regulatory approval from the Japanese Ministry of Health, Labor and Welfare (MHLW) for ABILIFY as the first antsipsychotic drug in Japan to treat...

http://japan.pharmaintellect.com/2013/06/abilify-granted-additional-approval-as.html?utm_source=feedburner&utm_medium=email&utm_campaign=Feed%3A+Pharmainvest+%28PharmaInvest%29

Ibrutinib Phase 2 Data: Analyses Show Efficacy with Ibrutinib Monotherapy in Patients with Relapsed or Refractory Mantle Cell or Diffuse Large B-cell Lymphoma

ibrutinib

June 16, 2013 

Janssen Research & Development, LLC (Janssen), today announced the results of two separate Phase 2 studies suggesting that ibrutinib, an investigational oral Bruton's tyrosine kinase (BTK) inhibitor, shows efficacy when used as a monotherapy in patients with relapsed/refractory mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL). The studies were presented today at the European Hematology Association (EHA) 18^th Annual Congress in Stockholm, Sweden. Ibrutinib is being jointly developed by Janssen and Pharmacyclics, Inc.

Ibrutinib (USAN), also known as PCI-32765, is an experimental drug candidate for the treatment of various types of cancer. It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton tyrosine kinase (Btk).

Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson's Janssen Pharmaceutical division for B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and multiple myeloma.

Ibrutinib was first designed and synthesized at Celera Genomics by Zhengying Pan, who along with a team of chemists and biologists reported in 2007 a structure-based approach for creating a series of small molecules that inactivate BTK through covalent binding to cysteine-481 near the ATP binding domain of BTK[2]. 

These small molecules irreversibly inhibited BTK by using a Michael acceptor for binding to the target cysteine. 

In April 2006, Pharmacyclics acquired Celera’s small molecule BTK inhibitor discovery program, which included a compound, PCI-32765 (known as compound 13 in the Pan et al paper) that was subsequently chosen for further preclinical development based on the discovery of anti-lymphoma properties in vivo . 

Since 2006, Pharmacyclics’ scientists have advanced the molecule into clinical trials and identified specific clinical indications for the drug.  It also has potential effects against autoimmune arthritis.

Pharma-Execs-2012-Pipeline-Report

 
Just days before this article went to press, FDA approved the first of a new kind of oral enzyme treatment that mediates cellular response, Incyte/Novartis' Jakafi, for a rare bone marrow disease called myelofibrosis. The next JAK inhibitor, Pfizer's toficitinib, could hit the market late next year, meaning a lot of rheumatoid arthritis patients will never again have to sit in a hospital for a couple of hours to get an anti-TNF infusion. Many innovative drugs, long out of the gate, are closing in on the finish line; science is back, and a better understanding of the way genomics shapes disease is bringing about better outcomes, and sometimes faster approvals.

read all at

http://www.pharmexec.com/pharmexec/Deals/Pharm-Execs-2012-Pipeline-Report/ArticleStandard/Article/detail/752361?contextCategoryId=48159

Amgen, Cytokinetics expand collaboration

Omecamtiv mecarbil

Omecamtiv mecarbil

Omecamtiv mecarbil

Omecamtiv mecarbil

Omecamtiv mecarbil
Amgen, Cytokinetics expand collaboration

Thursday, June 13, 2013 01:30 PM

Amgen and Cytokinetics, a clinical-stage biopharmaceutical company, have expanded their strategic collaboration to include Japan. In 2006, Cytokinetics and Amgen entered into a collaboration to discover, develop and commercialize novel small-molecule therapeutics that activate cardiac muscle contractility for potential applications in the treatment of heart failure. Omecamtiv mecarbil is the most advanced drug candidate in this collaboration.

- See more at:
 http://www.centerwatch.com//news-online/article/4852/amgen-cytokinetics-expand-collaboration

 Omecamtiv mecarbil , previously codenamed CK-1827452, is a cardiac specific myosin activator. It is clinically tested for its role in the treatment of left ventricular systolic heart failure. Systolic heart failure is characterised as a decreased cardiac output (<40% ejection fraction), due to decreased stroke volume, resulting in the inability to meet the metabolic demands of the body. The loss of contraction is caused by a reduced number of effective actin-myosin cross bridges in the left ventricular myocytes. One possible underlying mechanism is altered signal transduction that interferes with excitation-contraction coupling. A decreased cardiac output causes peripheral hypotension and activation of the sympathetic nervous system. This in turn stimulates the cardiac myocytes excessively, eventually leading to left ventricular hypertrophy, characteristic of chronic heart failure. Some symptoms of systolic heart failure are fatigue, peripheral oedema, dyspnoea, exercise intolerance and breathlessness. Current inotropic drug therapies such as dobutamine, are palliative and not a cure. They also cause many adverse effects including arrhythmias related to increased myocardical oxygen consumption, desensitization of adrenergic receptors and altering intracellular calcium levels. Thus systolic heart failure is considered malignant, however the novel mechanism of Omecamtiv Mecarbil is a hopeful long-term resolution.

The Design, Development and Scale-Up of Safe Chemical Processes and Operations

2 - 4 October 2013 • Chilworth Global, Princeton, NJ, USA

Dr Vahid Ebadat, Chilworth Technology Inc.

Dr. Swati Umbrajkar

Dr Will Watson, Scientific Update

http://ecampaign.scientificupdate.co.uk/index.php?action=social&c=17c276c8e723eb46aef576537e9d56d0.882

Developing safe processes is of paramount importance to any chemical company. Exothermic chemical reactions in batch and semi- batch processes can result in serious injury to people and plant if they get out of control. Results of thermal runaways include violent loss of containment, possibly explosion and the release of flammable or toxic materials to the environment.
Employers are bound by Health & Safety legislation to ensure the safety of their employees and those outside their employment who might be affected by their activities. Chemical manufacturers must therefore be aware of all potential dangers in their processes and take steps to eliminate them. The best approach is to design safety into the process from the start.
This seminar is designed to enhance the awareness of chemists and engineers regarding hazard issues. Utilizing the expertise of the chemists and chemical engineers at Chilworth Global and Scientific Update, it will consider hazard control of new chemical processes throughout their development cycle: from early development through to full-scale production. Hazards can often be eliminated by appropriate choice of reagent or synthetic route at the R&D stage. Where this is not possible, techniques exist to quantify the hazards so that robust engineering solutions can he applied in production.

Who Should Attend?

• R&D and Process Development Chemists, Chemical Engineers, Managers and anyone whose responsibilities include safety or risk assessment of chemical processes or building safety into chemical process scale-up.

Visit SCIENTIFIC UPDATE website for complete course information.

http://ecampaign.scientificupdate.co.uk/index.php?action=social&c=17c276c8e723eb46aef576537e9d56d0.882