| 1. |
- Bredberg, Anders, et al.
(author)
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Targeting versus tinkering: Explaining why the clinic is frustrated with molecular mapping of disease mechanisms.
- 2013
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 81:4, s. 553-556
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Journal article (peer-reviewed)abstract
- We argue that our common diseases should not necessarily be taken as a sign of physiological error. Regulatory networks developed by evolutionary forces to support reproductive fitness happen to include disease as a side-effect. For example, inflammatory and autoimmune diseases are secondary to a strong defence against infections. An evolutionary perspective can help us understand why many drugs targeted to single molecules or linear signaling pathways fail in clinical trials. We present the hypothesis that a tinkering research strategy, as compared with the prevailing reductionist approach, may be more likely to help us find the tools needed to interfere optimally with disease-generating networks. One application of the hypothesis can be to analyze how manipulation with diet and gut microbial flora influences multiple sclerosis patients, rather than to first map in detail the molecular disease mechanism and then develop targeting drugs.
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| 2. |
- Jamshidi, Nima, et al.
(author)
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Design and testing of statistical methods to classify the severity of steppage gait based on center of pressure data
- 2012
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 79:3, s. 334-337
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Journal article (peer-reviewed)abstract
- In this research kinematics parameters derived from ground reaction forces were evaluated to limit differential diagnoses and measure the degree of disabilities during walking among neuropathic subjects. 25 neuropathic subjects affected by drop foot and 20 normal subjects were enrolled in the study. Each subject was tested in average 10 ± 2 times for calculating kinetics parameters derived from ground reaction forces. The results revealed that the center of pressure displacement pattern in sole of foot can be a good index for differential diagnoses and measuring the degree of disabilities. This research can extend the clinical applications of ground reaction force plate and introduce suitable criteria to measure the degree of disability among neuropathic patients. © 2012 Elsevier Ltd.
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| 3. |
- Kumar, Arvind, et al.
(author)
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Information homeostasis as a fundamental principle governing the cell division and death
- 2011
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In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 77:3, s. 318-322
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Journal article (peer-reviewed)abstract
- To express the genetic information with minimal error is one of the key functions of a cell. Here we propose an information theory based, phenomenological model for the expression of genetic information. Based on the model we propose the concept of 'information homeostasis' which ensures that genetic information is expressed with minimal error. We suggest that together with energy homeostasis, information homeostasis is a fundamental working principle of a biological cell. This model proposes a novel explanation of why a cell divides and why it stops to divide and, thus, provides novel insights into oncogenesis and various neuro-degenerative diseases. Moreover, the model suggests a theoretical framework to understand cell division and death, beyond specific biochemical pathways.
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| 4. |
- Landin-Olsson, Mona, et al.
(author)
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Is type 1 diabetes a food-induced disease?
- 2013
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 81:2, s. 338-342
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Journal article (peer-reviewed)abstract
- The incidence of type 1 diabetes among children has almost doubled during the last decades in Sweden. Type 1 diabetes is considered as an autoimmune disease with unknown aetiology. Here we propose that the immune reaction may be initiated by food-derived mechanisms. The incidence of diabetes parallels an increased consumption of pasta, white bread, meat, cheese, low-fat milk, exotic fruits, soda, and snacks. Simultaneously, the consumption of potatoes, butter, high-fat milk, and domestic fruit has decreased. Three categories of food related reaction mechanisms are discussed against the following items (1) proteins from wheat, meat, and milk, (2) fat from processed food, and (3) exotic fruits. The current food consumption is suggested to initiate a pro-inflammatory reaction in the intestine and thereby reduce the intestinal barrier function. This may influence tolerance development and thus pave the way for an autoimmune attack on pancreatic beta cells.
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| 5. |
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| 6. |
- Lövheim, Hugo
(author)
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A new three-dimensional model for emotions and monoamine neurotransmitters
- 2012
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In: Medical Hypotheses. - : Elsevier BV. - 0306-9877 .- 1532-2777. ; 78:2, s. 341-348
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Journal article (peer-reviewed)abstract
- The monoamines serotonin, dopamine and noradrenaline have a great impact on mood, emotion and behavior. This article presents a new three-dimensional model for monoamine neurotransmitters and emotions. In the model, the monoamine systems are represented as orthogonal axes and the eight basic emotions, labeled according to Tomkins, are placed at each of the eight possible extreme values, represented as corners of a cube. The model may help in understanding human emotions, psychiatric illness and the effects of psychotropic drugs. However, further empirical studies are needed to establish its validity. (C) 2011 Elsevier Ltd. All rights reserved.
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| 7. |
- Pikwer, Andreas
(author)
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Depersonalization disorder may be related to glutamate receptor activation imbalance.
- 2011
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 77, s. 593-594
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Journal article (peer-reviewed)abstract
- Low-dose ketamine administration mimics, both clinically and on gross neuroimaging, depersonalization disorder. The perceptual effects of ketamine may be due to secondary stimulation of glutamate release and lamotrigine, possibly by inhibited glutamate release, may reduce some of ketamine's so-called dissociative effects. However, lamotrigine does not seem to be useful in the treatment of depersonalization disorder. Glutamate release in prefrontal cortex is increased by subanaesthetic doses of ketamine, resulting in increased inhibition, possibly via intercalated GABAerg cells, of projections from amygdala, affecting structures critically involved in depersonalization. I speculate that, in depersonalization disorder, the increased glutamate activity in prefrontal cortex is due to intrinsic imbalance, resulting in long-term potentiation, at the postsynaptic glutamate receptors on the GABAerg interneurons while the same receptor abnormality at the synapses on the intercalated GABAerg cells of the amygdala result in long-term depression in the case of either normal or high glutamate release.
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| 8. |
- Redfors, Björn, et al.
(author)
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Are the different patterns of stress-induced (Takotsubo) cardiomyopathy explained by regional mechanical overload and demand: Supply mismatch in selected ventricular regions?
- 2013
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In: Medical hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 81:5, s. 954-960
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Journal article (peer-reviewed)abstract
- Takotsubo cardiomyopathy (TCM) or stress-induced cardiomyopathy is an increasingly recognized syndrome characterized by severe regional left ventricular dysfunction in the absence of an explanatory coronary lesion. TCM may lead to lethal complications but is completely reversible if the patient survives the acute phase. The pathogenesis of TCM and the mechanism behind this remarkable recovery are unknown. Plasma levels of catecholamine are elevated in many TCM patients and exogenously administered catecholamine induces TCM-like cardiac dysfunction in both humans and rats. A catecholamine excess increases myocardial metabolic demand by increasing the force of contraction as well as the heart rate, and also alters cardiac depolarization patterns. We propose that an altered spatiotemporal pattern of cardiac contraction and excessive force of contraction may lead to a redistribution of wall stresses in the left ventricle. This redistribution of wall stress causes regional mechanical overload of regions where wall tension becomes disproportionately great and renders these cardiomyocytes "metabolically insufficient". In other words, these cardiomyocytes experience a demand: supply mismatch on the basis of excessive metabolic demand. In order to prevent the death of these cardiomyocytes and to prevent excessive wall tension from developing in neighboring regions, a protective metabolic shutdown occurs in the affected cardiomyocytes. This metabolic shutdown, i.e., acute down regulation of non-vital cellular functions, serves to protect the affected regions from necrosis and explains the apparently complete recovery observed in TCM. We propose that this phenomenon may share important characteristics with phenomena such as ischemic conditioning, stunning and hibernation. In this manuscript, we discuss our hypothesis in the context of available knowledge and discuss important experiments that would help to corroborate or refute the hypothesis.
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| 9. |
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| 10. |
- Sodersten, P, et al.
(author)
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Obesity and the brain
- 2011
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In: Medical hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 77:3, s. 371-373
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Journal article (peer-reviewed)
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| 11. |
- Stenman, Emelie, et al.
(author)
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Increased monoaminergic neurotransmission improves compliance with physical activity recommendations in depressed patients with fatigue.
- 2012
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877.
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Journal article (peer-reviewed)abstract
- Clinical studies have shown that moderately intense physical activity effectively treats various types of depression. Beneficial effects have been reported in the acute phase of the disease as well as in a long-term perspective. In addition, epidemiological studies have shown that inactivity increases the risk of depression and that exercise prevents relapse. Depressed patients are often prescribed antidepressants, with or without psychotherapy. Some studies have, however, suggested that the most frequently used antidepressants, selective serotonin reuptake inhibitors (SSRIs), contribute to fatigue, which is a common residual symptom associated with depression and the target of the proposed study. Profound fatigue may in turn decrease the ability and motivation to perform the beneficial physical activity, e.g. via executive dysfunction. Fatigue and impaired executive function are commonly linked to disturbed cerebral dopaminergic and noradrenergic neurotransmission. This kind of dysfunction is hard to overcome, even when the major symptoms of depression are alleviated. Interestingly, physical activity has been suggested to improve the dopamine and norepinephrine neurotransmission. Furthermore, the favorable effects may be reciprocal; improved dopamine and norepinephrine transmission in the brain may hypothetically increase the ability and motivation to exercise, since some parts of the brain (e.g. the prefrontal cortex, striatum and cerebellum) that control movement and initiative receive dopaminergic and noradrenergic projections. Based on these findings and assumptions, our hypothesis is that increased dopaminergic and noradrenergic neurotransmission, via intake of a dopamine- and norepinephrine-enhancing agent, improves the compliance with prescribed physical activity in patients with depression and residual fatigue. We also believe that the increased physical activity can prevent relapse into depression, even after interruption of medication. Since increased physical activity also has been shown to improve executive cognitive function, we suggest that executive function should be examined as a secondary outcome together with other possibly related variables such as quality of life, sick leave and BMI.
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| 12. |
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| 13. |
- Wilder-Smith, Annelies, et al.
(author)
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Hypothesis : Impregnated school uniforms reduce the incidence of dengue infections in school children
- 2011
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In: Medical Hypotheses. - : Elsevier. - 0306-9877 .- 1532-2777. ; 76:6, s. 861-862
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Journal article (peer-reviewed)abstract
- Dengue infection causes a significant economic, social and medical burden in affected populations in over 100 countries in the tropics and sub-tropics. Current dengue control efforts have generally focused on vector control but have not shown major impact. School-aged children are especially vulnerable to infection, due to sustained human-vector-human transmission in the close proximity environments of schools. Infection in children has a higher rate of complications, including dengue hemorrhagic fever and shock syndromes, than infections in adults. There is an urgent need for integrated and complementary population-based strategies to protect vulnerable children. We hypothesize that insecticide-treated school uniforms will reduce the incidence of dengue in school-aged children. The hypothesis would need to be tested in a community based randomized trial. If proven to be true, insecticide-treated school uniforms would be a cost-effective and scalable community based strategy to reduce the burden of dengue in children.
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| 14. |
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