[Dr Jean Languillon (1912-2003), a major unrecognized leprologist]. / Le Dr Jean Languillon (1912-2003), un léprologue majeur trop méconnu.

Languillon's contribution to the control of leprosy cannot be reduced to the manual of leprology which remains the reference for anyone working on this disease in sub-Saharan Africa. This would mean forgetting his works that established the immunological origin of leprosy and its cutaneous, adverse and neurological complications.Another major aspect, the importance of his contribution to the treatment of the disease, in particular through the development of polychimiotherapy (PCT), which has made Institut Marchoux in Bamako one of the five WHO's collaborating centers in the field of clinical research in leprosy.Languillon was also involved in a holistic approach of the disease by creating the first leprosy surgery unit and implementing physiotherapy, orthopedic care with appropriate equipment, and social rehabilitation… without forgetting preventive aspects of complications through the necessary regular administration of treatments, and control of patients spread over wide territories, by creating a corps of leprosy nurse monitors and leprosy specialists. These will provide essential support to the doctor most often in charge of a huge sector where the need of assistance was obvious.Languillon ended his African career by creating the ILAD, Institute of Applied Leprology in Dakar, which offers the full range of care, as he always advocated.Finally, he did not resist the call of Order of Malta which offered him to share his expertise in the different countries where the Order was involved.

[Snakes as a source of drugs from the Han to the Song Dynasties].

This paper examined the history of snakes as a source of drugs from the Han to the Song Dynasties. Snake products, for medicinal purposes, were not widely used in the Han, Wei and Jin Dynasties out of worship and fear of snakes.The source of snake products taken for medical purposes might be partly because local people ate snakes in the South area. Palace snakes and pit viper products were taken as drugs in the Tang Dynasty for the treatment of leprosy and ulcers of the female external genitals. Zaocysdhumnades were seldom used as medicine because they were not recorded in medical documents in the Tang Dynasty, but only seen in some notes. They were widely used in medical practice in the late Tang and the early Song Dynasties and were formally recorded in medical documents for the diseases caused by Wind. Their effectiveness, rarity, high value and toxicity contraindication were repeatedly stressed while palace snakes and pit vipers were seldom mentioned and used.

Dimitrios Zambakis' Scientific Hypothesis on the Transmission of Leprosy.

Dimitrios Zambakis was an acclaimed physician at his time, most recognized for his work on leprosy. He theorized that leprosy was a hereditary disease, receiving many awards for his work including the Cholera Medal of Honour (1854), Château-Villard Prize from the Faculty of Medicine in Paris (1898), The Montyon Prize, and the title of Pasha. However, his theory was routinely argued against and was later proven to be invalid. Leprosy is regarded as a contagious disease spread by contact and is not hereditary. The last name appears to be spelled in various ways (Zambakis, Zambaco). For this paper, "Dimitrios Zambakis" will be used.

Fundación Neumológica Colombiana 30 años de una institución con espíritu / Fundación Neumológica Colombiana 30 years of an institution with spirit

Hablar de la Neumología moderna en Colombia y de la Fundación Neumológica Colombiana es hablar de Darío Maldonado Gómez. Nacido en Pamplona, Norte de Santander, llegó a Bogotá siendo un adolescente, cuando sus padres se vieron obligados a salir de su ciudad natal hacia la capital, con todos sus hijos, producto de la violencia encendida a finales de la década de los 40´s. Con el ejemplo de su padre, Darío Maldonado Romero, médico que se especializó en la lepra y consagró sus esfuerzos al desarrollo de políticas de salud pública. Así, con la ambición de aprender y apropiar la ciencia, el arte y el humanismo que sustentan la medicina, ingresó a la Universidad Nacional en Bogotá y obtuvo su título de médico en 1959. Su ánimo de aprender y de poder ofrecer siempre las mejores opciones a sus pacientes, lo llevaron pronto a Chicago y Milwaukee, Estados Unidos, donde, en la década de los 60´s, se entrenó en Medicina Interna y Neumología con el profesor Gordon Snider, pionero y figura de la Neumología moderna en el mundo.

Talking about modern Pulmonology in Colombia and the Colombian Pulmonary Foundation is talking about Darío Maldonado Gómez. Born in Pamplona, Norte de Santander, he came to Bogotá as a teenager, when his parents were forced to leave their hometown for the capital, with all their children, as a result of the violence inflamed at the end of the 1940s. With the example of his father, Darío Maldonado Romero, a doctor who specialized in leprosy and devoted his efforts to the development of public health policies. Thus, with the ambition of learning and appropriating the science, art and humanism that sustain medicine, he entered the National University in Bogotá and obtained his medical degree in 1959. His desire to learn and to always be able to offer the best options to his patients, they soon took him to Chicago and Milwaukee, United States, where, in the 1960s, he trained in Internal Medicine and Pulmonology with Professor Gordon Snider, pioneer and figure of modern Pulmonology in the world.

Dr. Betty Clements: Breaking Gender Barriers in the Air Force and Neurology.

Women currently make up 45.9% of neurology residents and fellows, although little is known about the individual women who broke gender barriers to train as neurologists. Grace Elizabeth Betty Clements (1918-1965) was the first woman trainee at the Mayo Clinic to practice neurology and later became a founder of the Barrow Neurological Institute. Before paving the way for future women trainees in neurology, she served as a Women Airforce Service Pilot including flying atomic bomb planning missions during World War II. Following the war, her path to medicine included volunteering in the American Red Cross in the Philippines where she treated patients with Hansen disease (leprosy). Clements returned to her home state to complete medical school at the University of Nebraska before seeking neurologic training at the Mayo Clinic in 1954. Following additional training at Queen Square, she became a founder of the Barrow Neurological Institute in Phoenix, Arizona. Many early women in neurology have remarkable backgrounds that have equipped them for their career in medicine which Clements exemplifies.

[The history and influence of Losheng Sanatorium in Taiwan area].

Losheng Sanatorium, as a prophylactic-therapeutic institution for isolation, treatment, rehabilitation and social control of leprosy patients, was established by the Japanese colonial government in Taiwan in 1930. Losheng Sanatorium effectively carried out the compulsory isolation of leprosy patients, under the assistance of the public medical system with the help of police and the Bao-Jia management in the Japanese colonial period in Taiwan. Losheng sanatorium imported DDS, a therapeutic drug for leprosy, popularised an outpatient treatment model of leprosy, and developed mobile medical services after the Second World War. Losheng detected and treated leprosy patients successfully through the support of special skin clinics in public hospitals and missionary hospitals after Multi-drug Therapy was introduced in Taiwan in 1984. The Department of Health, Executive Yuan of the Taiwan area in commenced administration of Losheng Sanatorium in 1999 transformed it into a community-based general hospital. Losheng sanatorium adopted different control strategies in different historical periods based on the requirements of health, epidemic prevention systems and leprology developments to achieve its goals of leprosy control. The Sanatorium provides an example to understand and further study epidemical control and public health practice in the Taiwan area.

Demetrius Zambaco Pasha (1832-1913): The first leprologist of the Orient.

Démétrius Zambaco Pasha (1832-1913) was an internationally renowned Ottoman-born French dermatologist of Greek origin who is considered the first leprologist of the Orient. A graduate from the Faculty of Medicine in Paris, he practised there until he returned to Istanbul in 1872 and later served as a private physician to the Ottoman sultan Abdul Hamid II (1842-1918), then Abbas Hilmi Pasha (1874-1944), the last Khedive of Egypt. Dr Zambaco produced numerous publications in a variety of medical subjects including leprosy, syphilis, morphinomania, eunuchs, and medical history. Leprosy, however, was his main field of scientific interest, with nearly 40 studies published and many other communications presented at international medical congresses. Due to his outstanding scientific contributions, Dr Zambaco garnered many accolades including the Cholera Medal of Honour, the Montyon Prize, and Légion d'Honneur from France as well as the honorary title of Pasha, a higher rank in the political and military system, from the Ottoman Empire.

2,4 Dinitrophenol as Medicine.

In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950's to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin® and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescription, as both a sleeping pill and "morning sickness" anti-nausea medication targeting pregnant women in the 1950's. The "thalidomide babies" became the case-in-point for the need of strict guidelines by the U.S. Food & Drug Administration (FDA) or full multi-species teratogenicity testing before drug approval. More recently it was found that thalidomide is useful in graft versus host disease, leprosy and resistant tuberculosis treatment, and as an anti-angiogenesis agent as a breakthrough drug for multiple myeloma (except for pregnant female patients). Decades of diabetes drug discovery research has historically focused on every possible angle, except, the energy-out side of the equation, namely, raising mitochondrial energy expenditure with chemical uncouplers. The idea of "social responsibility" allowed energy-in agents to be explored and the portfolio is robust with medicines of insulin sensitizers, insulin analogues, secretagogues, SGLT2 inhibitors, etc., but not energy-out medicines. The primary reason? It appeared unorthodox, to return to exploring a drug platform used in the 1930s in over 100,000 obese patients used for weight loss. This is over 80-years ago and prior to Dr Peter Mitchell explaining the mechanism of how mitochondrial uncouplers, like 2,4-dinitrophenol (DNP) even worked by three decades later in 1961. Although there is a clear application for metabolic disease, it was not until recently that this platform was explored for its merit at very low, weight-neutral doses, for treating insidious human illnesses and completely unrelated to weight reduction. It is known that mitochondrial uncouplers specifically target the entire organelle's physiology non-genomically. It has been known for years that many neuromuscular and neurodegenerative diseases are associated with overt production of reactive oxygen species (ROSs), a rise in isoprostanes (biomarker of mitochondrial ROSs in urine or blood) and poor calcium (Ca2+) handing. It has also been known that mitochondrial uncouplers lower ROS production and Ca2+ overload. There is evidence that elevation of isoprostanes precedes disease onset, in Alzheimer's Disease (AD). It is also curious, why so many neurodegenerative diseases of known and unknown etiology start at mid-life or later, such as Multiple Sclerosis (MS), Huntington Disease (HD), AD, Parkinson Disease, and Amyotrophic Lateral Sclerosis (ALS). Is there a relationship to a buildup of mutations that are sequestered over time due to ROSs exceeding the rate of repair? If ROS production were managed, could disease onset due to aging be delayed or prevented? Is it possible that most, if not all neurodegenerative diseases are manifested through mitochondrial dysfunction? Although DNP, a historic mitochondrial uncoupler, was used in the 1930s at high doses for obesity in well over 100,000 humans, and so far, it has never been an FDA-approved drug. This review will focus on the application of using DNP, but now, repositioned as a potential disease-modifying drug for a legion of insidious diseases at much lower and paradoxically, weight neutral doses. DNP will be addressed as a treatment for "metabesity", an emerging term related to the global comorbidities associated with the over-nutritional phenotype; obesity, diabetes, nonalcoholic steatohepatitis (NASH), metabolic syndrome, cardiovascular disease, but including neurodegenerative disorders and accelerated aging. Some unexpected drug findings will be discussed, such as DNP's induction of neurotrophic growth factors involved in neuronal heath, learning and cognition. For the first time in 80's years, the FDA has granted (to Mitochon Pharmaceutical, Inc., Blue Bell, PA, USA) an open Investigational New Drug (IND) approval to begin rigorous clinical testing of DNP for safety and tolerability, including for the first ever, pharmacokinetic profiling in humans. Successful completion of Phase I clinical trial will open the door to explore the merits of DNP as a possible treatment of people with many truly unmet medical needs, including those suffering from HD, MS, PD, AD, ALS, Duchenne Muscular Dystrophy (DMD), and Traumatic Brain Injury (TBI).

The Molecular Mechanisms of Thalidomide Teratogenicity and Implications for Modern Medicine.

Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and antiangiogenic activities are considered in many other refractory diseases. The aim is to develop derivatives that are not teratogenic but maintain the therapeutic potential. This requires detailed knowledge about the underlying molecular mechanisms. Much progress has been made in deciphering the teratogenic mechanisms in the last decade. Here, we summarize these mechanisms, explain thalidomide resistance of rodents, and discuss possible mechanisms that could explain why the drug primarily targets the developing limb in the embryo. We also summarize the most important therapeutic mechanisms. Finally, we discuss which therapeutic and teratogenic mechanisms do and do not overlap, and if there is a chance for the development of non-teratogenic thalidomide derivatives with therapeutic potential.

[Overseas medical cooperation for elimination of leprosy].

The typical leprosy doctor is disappearing in Japan. One of the reasons for this is that no more new cases arise among people of Japanese nationality. Furthermore, among people of other nationality living in Japan, occurrence of the cases has become rare. At the same time, it has become difficult to get a new medical person for leprosy field because the interest for the overseas medical cooperation has become diversified and there is a misunderstanding that the problem of leprosy in the world has been resolved. However we need to keep speaking out that there are still much more to be done. When we fortunately have someone who wishes to become a leprologist, his/her training is only possible in the very site of NGO in developing countries. One may start his/her work by passionate motivation of "living together", but actually he/she needs to be nurtured by people there. Another way to get involved is to first become a specialist of some sort, and then get in a medical system of a developing country as a narrow range specialist, and while serving them there, one can deepen his/her experiences as a whole leprosy. It is also important for us to think how we accept people who have worked overseas. We need to investigate and construct the supporting system for them. As long as leprosy patients exist in the world who are still suffering, we, as Japanese, need to make efforts in continuously sending people who live with them.

Anticuerpos séricos antiglicolípido fenólico 1 en personal de centros de salud en contacto con pacientes con enfermedad de Hansen / Antiphenolic glycolipid-1 antibodies in personnel in health centers in contact with Hansen´s disease patients

La lepra es una enfermedad con diferentes formas clínicas, sin embargo, es poco el conocimiento que se tiene sobre portadores de Mycobacterium leprae (M. leprae), así como de su transmisión y los fenómenos inmunológicos que conllevan a la aparición de la enfermedad. El antígeno Glicolípido Fenólico 1 (PGL-1) es un factor de virulencia, específico del M. leprae que protege a la bacteria del ataque de los macrófago. El objetivo principal de la siguiente investigación fue detectar anticuerpos anti PGL-1 en el personal en contacto estrecho con pacientes con lepra, para conocer su grado de exposición al bacilo y su utilidad como factor de riesgo para sufrir la enfermedad. Se seleccionó un grupo de individuos (n: 52) en contacto frecuente con pacientes leprosos y un grupo control (n: 60) sin contacto demostrado. La presencia de anticuerpos séricos IgM anti PGL-1 se determinó por la técnica de ELISA. Del total analizado, se detectaron anticuerpos anti-PGL-1, en 22 muestras (42,3%) del grupo expuesto y 3 (5,0%) en el grupo control (p<0,05). No se observaron diferencas en relación al sexo (45,5% vs. 41,5%). Se encontró un predominio de la seropositividad en el personal entre 36 a 55 años, sin relación a los años de exposición. Se destaca una mayor frecuencia en el personal médico (73,3%) y un riesgo relativo de exposición al bacilo de la Lepra del 1.9 en la población expuesta. Estos resultados demuestran un mayor porcentaje de personas seropositivas al anti-PGL-1 en el personal de centros de salud, relacionado al grado de exposición al bacilo de Hansen, especialmente el personal médico. Hallazgos que sugieren riesgo incrementado de adquirir M. leprae con respecto a la población general. Se recomienda la toma de medidas de bioseguridad, así como realizar un seguimiento serológico de los casos positivos del presente estudio.

Lepra: algunas relaciones socioeconómicas en Venezuela / Leprosy: some socioeconomic relations in Venezuela

En Venezuela se alcanzó el criterio de eliminación de lepra- como problema de salud pública- (tasas inferiores a 1 caso por 10.000 hab) en 1997 a nivel nacional, sin embargo aún existen regiones del país, donde las tasas de enfermedad siguen siendo elevadas. Para el cálculo de prevalencia de lepra en cada uno de los estados del país, además de los casos informados por el Sistema de Información del Programa de Lepra, se toma en cuenta la posibles casos nuevos originados por individuos infectantes con diagnóstico tardíos que presumiblemente premanecen ocultos debido al largo período de incubación de la enfermedad. Se examina la distribución geográfica de la lepra, su relación con algunas características socioeconómicas de la población y con aspectos operacionales del programa de control de la enfermedad

Incremento de óxido nítrico en el suero y sobrenadantes de cultivo de células mononucleares de pacientes con la enfermedad de Hansen en estado reaccional tipo II / Increase in nitric oxide concentrations in serum and mononuclear cell cultures from patients with type II rection state of Hansen`s disease

El término "reacción" es usado en lepra para describir síntomas y signos de inflamación aguda. En la forma multibacilar de la enfermedad se producen reacciones tipo II, es decir, eritema nodoso lepromatoso (ENL). El óxido nítrico (ON) podría jugar un papel en la respuesta de huésped, donde la producción elevada de ON estaría involucrada en cuadros inflamatorios agudos. En este trabajo se evaluá la producción de ON en suero y en sobrenadantes de cultivos de células mononucleares (CMN). El ON fue medido indirectamente por el método de Griess. En suero, el 52 por ciento de los pacientes con ENL (15/29) presentó niveles de nitritos/nitratos mayores de 30 µM; así 8/15 presentaron una concentración de 36,38 ± 5,71 µM; 1/15 de 70,5 µM y 6/15 mayor de 100 µM (205,97 ± 5 µM). En concordancia con estos resultados, se encontró que sólo los sobrenadantes de cultivos de células mononucleares de los pacientes con ENL colectados a las 120 horas de incubación presentaron niveles significativamente elevados de nitritos/nitratos (10 µM ± 6,53), en comparación con los sobrenadantes de los polos estables de la enfermedad, lepra lepromatosa y lepra tuberculoide, cuyos valores fueron 2,52 µM ± 1,18 y 2,69 µM ± 1,07, respectivamente. Los resultados muestran niveles relativamente encrementados de nitritos/nitratros en el grupo de pacientes con estado reaccional tipo II (ENL), lo cual sugiere la participación de la iNOS en este grupo

Essentially christian eminently philanthropic the mission to lepers in british India

A história antiga da Missão para leprosos na India é a história das relações entre a política, a religião e a medicina, dentro do contexto do imperialismo britânico.A Missão perseguia o par de objetivos inseparáveis da evangelização e da civilização, desenvolvendo não só um programa religioso, como também um político e cultural. Tais atividades e suas consequências eram multifacetadas, porque enquanto os missionários seguiam sua vocação religiosa, eles também forneciam cuidados médicos a pessoas e lugares que o governo colonial não podia ou não queria atender. Dentro do contexto do programa imperial britânico, o trabalho dos missionários passava ideais sociais e culturais ocidentais para as populações a que serviam, inculcando nos pacientes as crenças cristãs e oferecendo cuidados médicos a indivíduos que haviam sido expulsos de suas comunidades. A cura do físico estava intimamente ligada à salvação da alma, à cura espiritual e ao processo civilizatório