Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
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Severe acute respiratory syndrome (SARS) originated in Southern China in November 2002, and was brought to Hong Kong in February 2003. From Hong Kong, the disease spread rapidly worldwide but mostly to Asian countries. At the end of the epidemic in June, the global cumulative total was 8422 cases with 916 deaths (case fatality rate of 11%). People of all ages were affected, but predominantly females. Health care workers were at high risk and accounted for one-fifth of all cases. Risk factors for death included old age and comorbid illnesses, especially diabetes. The disease is caused by a novel coronavirus and is transmitted by droplets or direct inoculation from contact with infected surfaces. Contaminated sewage was found to be responsible for the outbreak in a housing estate in Hong Kong affecting over 300 residents. The mean incubation period was 6.4 days (range 2-10). The duration between onset of symptoms and hospitalisation was from 3 to 5 days. The relatively prolonged incubation period allowed asymptomatic air travellers to spread the disease globally. The number of individuals infected by each case has been estimated to be 2.7. Effective control of nosocomial transmission included early detection of disease, strict isolation of patients, practice of droplet and contact precautions and compliance with the use of personal protective equipment. Effective control of disease spread in the community included tracing and quarantine of contacts. Development of a validated diagnostic test and an effective vaccine as well as elimination of possible animal reservoirs are measures needed to prevent another epidemic.
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PMID:SARS: epidemiology. 1501 27

Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy is an autoimmune peripheral-nerve and/or nerve-root disorder known to usually respond to intravenous immunoglobulin-G treatment. Benefit can involve any combination of motor-nerve fibers and large and small sensory-nerve fibers responsible for a progressively crippling, unbalancing, discomforting or painful disorder. "Diabetic neuropathy" is commonly considered untreatable. However, 81% of my 48 recently-summarized type-2 diabetes patients with polyneuropathy, adequately-treated with intravenous immunoglobulin-G, off-label, were relieved, sometimes completely, of various motor and sensory symptoms, including pain, thereby resembling Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy. Spinal fluid protein in them is often elevated, higher values seeming to auger a better intravenous immunoglobulin-G response. Continuing the improvement requires continuing the intravenous immunoglobulin-G treatment, indicating both intravenous immunoglobulin-G responsiveness and dependency. The intravenous immunoglobulin-G responsive type-2 diabetes polyneuropathy usually is dysschwannian, sometimes mainly dysneuronal intravenous immunoglobulin-G, the most beneficial and safest treatment, is costly, but if intravenous immunoglobulin-G-treatability of a dysimmune component of type-2 diabetes neuropathy is overlooked, dismissed or rejected, as commonly happens, other costs are high regarding the patient's worsening morbidity and disability, and resultant need for increased medical care. A novel intravenous immunoglobulin-G regimen effective for fragile patients is Two Non-Consecutive-Days Every Week, using 0.4 gm/kg body wt/day. Possible molecular mechanisms of intravenous immunoglobulin-G benefit are discussed. I propose that a) there is a higher incidence of Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy-like neuropathy in type-2 diabetes patients and in patients with a strong family history of type-2 diabetes, and b) the intravenous immunoglobulin-G-treatable neuropathy in type-2 diabetes can be brought on by the genetico-diabetoid-2 state. The genetic-metabolic milieu (but not necessarily glucose dysmetabolism per se.) of type-2 diabetes putatively predisposes to the presumably-dysimmune intravenous immunoglobulin-G-responsive polyneuropathy. In some of our patients, especially ones having a strong type-2 diabetes genetic background, the intravenous immunoglobulin-G-responsive neuropathy preceded the diagnosis of type-2 diabetes by 5-10 years. Accordingly, Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy patients having a strong type-2 diabetes genetic background are designated "genetico-diabetoid-2 neuropathy" prior to their manifesting type-2 diabetes. Intravenous immunoglobulin-G is herein suggested as a treatment for Severe Acute Respiratory Syndrome, a recent, and feared-repetitive, pandemic with many fatalities caused by a highly-contagious mutant coronavirus, for which there is no definitive treatment. Intravenous immunoglobulin-G might: a) combat a dysimmune component of Severe Acute Respiratory Syndrome, including the reactive cytokine-chemokine storm against respiratory tissues; b) contain some antibodies effective against the coronavirus non-specific components of Severe Acute Respiratory Syndrome; c) block host-cell receptors for the virus; and d) counteract secondary infections.
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PMID:Intravenous immunoglobulin G is remarkably beneficial in chronic immune dysschwannian/dysneuronal polyneuropathy, diabetes-2 neuropathy, and potentially in severe acute respiratory syndrome. 1508 99

The zinc metallopeptidase angiotensin-converting enzyme 2 (ACE2) is the only known human homologue of the key regulator of blood pressure angiotensin-converting enzyme (ACE). Since its discovery in 2000, ACE2 has been implicated in heart function, hypertension and diabetes, with its effects being mediated, in part, through its ability to convert angiotensin II to angiotensin-(1-7). Unexpectedly, ACE2 also serves as the cellular entry point for the severe acute respiratory syndrome (SARS) virus and the enzyme is therefore a prime target for pharmacological intervention on several disease fronts.
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PMID:ACE2: from vasopeptidase to SARS virus receptor. 1516 41

Severe acute respiratory syndrome (SARS) is a new respiratory viral epidemic that originated in China but has affected many parts of the world, with devastating impact on economies and the practice of medicine and rehabilitation. A novel coronavirus has been implicated, with transmission through respiratory droplets. Rehabilitation was significantly affected by SARS, because strict infection control measures run counter to principles such as multidisciplinary interactions, patients encouraging and learning from each other, and close physical contact during therapy. Immunocompromised patients who may silently carry SARS are common in rehabilitation and include those with renal failure, diabetes, and cancer. Routine procedures such as management of feces and respiratory secretions (eg, airway suctioning, tracheotomy care) have been classified as high risk. Personal protection equipment presented not only a physical but also a psychologic barrier to therapeutic human contact. Visitor restriction to decrease chances of disease transmission are particularly difficult for long-staying rehabilitation patients. At the height of the epidemic, curtailment of patient movement stopped all transfers for rehabilitation, and physiatrists had to function as general internists. Our experiences strongly suggest that rehabilitation institutions should have emergency preparedness plans because such epidemics may recur, whether as a result of nature or of bioterrorism.
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PMID:Impact of a viral respiratory epidemic on the practice of medicine and rehabilitation: severe acute respiratory syndrome. 1529 68

Angiotensin-converting enzyme-2 (ACE2) is the first human homologue of ACE to be described. ACE2 is a type I integral membrane protein which functions as a carboxypeptidase, cleaving a single hydrophobic/basic residue from the C-terminus of its substrates. ACE2 efficiently hydrolyses the potent vasoconstrictor angiotensin II to angiotensin (1-7). It is a consequence of this action that ACE2 participates in the renin-angiotensin system. However, ACE2 also hydrolyses dynorphin A (1-13), apelin-13 and des-Arg(9) bradykinin. The role of ACE2 in these peptide systems has yet to be revealed. A physiological role for ACE2 has been implicated in hypertension, cardiac function, heart function and diabetes, and as a receptor of the severe acute respiratory syndrome coronavirus. This paper reviews the biochemistry of ACE2 and discusses key findings such as the elucidation of crystal structures for ACE2 and testicular ACE and the development of ACE2 inhibitors that have now provided a basis for future research on this enzyme.
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PMID:Angiotensin-converting enzyme-2: a molecular and cellular perspective. 1554 71

In the future, transfer of vital sensor data from patients to the public health care system is likely to become commonplace. Systems for automatic transfer of sensor data are now at the prototype stage. As electronic health record (EHR) systems adapt such functionality, widespread use may become an actuality in the foreseeable future.To prevent spreading of diseases, an early detection of infection is important. At the time an outbreak is diagnosed, many people may already be infected due to the incubation period. This study suggests an approach for detecting an epidemic outbreak at an early stage by monitoring blood glucose data collected from people with diabetes. Continuous analysis of blood glucose data may have the potential to prevent large outbreaks of infectious diseases, such as different strains of Influenza, Cholera, Plague, Ebola, Anthrax and SARS.When a person gets infected, the blood glucose value increases. If the blood glucose data from a large number of patients with diabetes are collected in a central database, it may be possible to detect an epidemic disease outbreak at an early stage. Advanced data analysis on the data may detect predominant numbers of incidences, indicating a possible outbreak. This gives the health authorities the possibilities to take actions to limit the outbreak and its consequences for all the inhabitants in an affected area.At the Norwegian Centre for Telemedicine, a mobile system for automatic transfer of blood glucose values has been constructed. By using wireless communication standards such as Bluetooth and GSM, the system transfers blood glucose data to an electronic health record system. Combined with a system accessing and querying data from EHR systems for patient surveillance we are extending our work into an Epidemic Disease Detection using blood Glucose (EDDG) system.
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PMID:Using blood glucose data as an indicator for epidemic disease outbreaks. 1616 Feb 62

The renin-angiotensin-aldosterone system (RAAS) is a key regulator of systemic blood pressure and renal function and a key player in renal and cardiovascular disease. However, its (patho)physiological roles and its architecture are more complex than initially anticipated. Novel RAAS components that may add to our understanding have been discovered in recent years. In particular, the human homologue of ACE (ACE2) has added a higher level of complexity to the RAAS. In a short period of time, ACE2 has been cloned, purified, knocked-out, knocked-in; inhibitors have been developed; its 3D structure determined; and new functions have been identified. ACE2 is now implicated in cardiovascular and renal (patho)physiology, diabetes, pregnancy, lung disease and, remarkably, ACE2 serves as a receptor for SARS and NL63 coronaviruses. This review covers available information on the genetic, structural and functional properties of ACE2. Its role in a variety of (patho)physiological conditions and therapeutic options of modulation are discussed.
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PMID:The emerging role of ACE2 in physiology and disease. 1746 36

Multiple organ damage in severe acute respiratory syndrome (SARS) patients is common; however, the pathogenesis remains controversial. This study was to determine whether the damage was correlated with expression of the SARS coronavirus receptor, angiotensin converting enzyme 2 (ACE2), in different organs, especially in the endocrine tissues of the pancreas, and to elucidate the pathogenesis of glucose intolerance in SARS patients. The effect of clinical variables on survival was estimated in 135 SARS patients who died, 385 hospitalized SARS patients who survived, and 19 patients with non-SARS pneumonia. A total of 39 SARS patients who had no previous diabetes and received no steroid treatment were compared to 39 matched healthy siblings during a 3-year follow-up period. The pattern of SARS coronavirus receptor-ACE2 proteins in different human organs was also studied. Significant elevations in oxygen saturation, serum creatinine, lactate dehydrogenase, creatine kinase MB isoenzyme, and fasting plasma glucose (FPG), but not in alanine transaminase were predictors for death. Abundant ACE2 immunostaining was found in lung, kidney, heart, and islets of pancreas, but not in hepatocytes. Twenty of the 39 followed-up patients were diabetic during hospitalization. After 3 years, only two of these patients had diabetes. Compared with their non-SARS siblings, these patients exhibited no significant differences in FPG, postprandial glucose (PPG), and insulin levels. The organ involvements of SARS correlated with organ expression of ACE2. The localization of ACE2 expression in the endocrine part of the pancreas suggests that SARS coronavirus enters islets using ACE2 as its receptor and damages islets causing acute diabetes.
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PMID:Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. 1933 47

Facing escalating health care expenditures, the governments of countries with national health insurance programs are trying to control or even to reduce health care utilization. Little research has examined the effects of decreased health care utilization on health outcomes. Applying a natural experiment design to the Taiwan population between 2000 and 2004, which includes the 2003 SARS epidemic when an average 20% decline in health care utilization occurred, this study examines the association between a decline in health care utilization and health outcomes measured by cause-specific mortality rates. We analyse the monthly mortality rates caused by infectious diseases, cancer, diabetes mellitus, nervous system diseases, cerebrovascular diseases, heart and other vascular diseases, respiratory system diseases, digestive system diseases, genitourinary system diseases and accidents. Models control for age, sex, month and year effects. Results show the heterogeneous effect of reduced health care utilization on health outcomes. Patients with diabetes mellitus or cerebrovascular diseases are vulnerable to short-term reductions in health care; compared with the non-SARS period, mortality caused by diabetes mellitus and cerebrovascular diseases significantly increased during the SARS epidemic by 8.4% and 6.2%, respectively. No significant change in mortality rates caused by the other diseases or accidents is found. This study suggests that governments of countries where health care utilization and spending are similar to or inferior to those in Taiwan should carefully evaluate the impact of policies that attempt to reduce health care utilization. Furthermore, when an area encounters an epidemic, governments should be aware of the negative consequences of voluntary restraints on access to health care that accompany decreases in utilization.
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PMID:Health care utilization and health outcomes: a population study of Taiwan. 2225 70

In the early treatment of diabetes with vanadium, inorganic vanadium compounds have been the focus of attention; organic vanadium compounds are nowadays increasingly attracting attention. A key compound is bis(maltolato)oxidovanadium, which became introduced into clinical tests Phase IIa. Organic ligands help modulate the bioavailability, transport and targeting mechanism of a vanadium compound. Commonly, however, the active onsite species is vanadyl (VO(2+)) or vanadate (H(2)VO(4) (-)), generated by biospeciation. The mode of operation can be ascribed to interaction of vanadate with phosphatases and kinases, and to modulation of the level of reactive oxygen species interfering with phosphatases and/or DNA. This operating mode has also been inferred for most cancerostatic vanadium compounds, although some, for example vanadocenes, may directly intercalate with DNA. Novel medicinal potentiality of vanadium compounds is geared towards endemic diseases in tropical countries, in particular leishmaniasis, Chagas' disease and amoebiasis, and viral infections such as Dengue fever, SARS and HIV.
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PMID:The potentiality of vanadium in medicinal applications. 2304 79


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