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- Exploiting nanoparticle for targeted apoptosis as therapeutic modality
against filarial parasite: A plausible premise.
Abstract: Introduction: Under the flagship of tropical disease research programme of WHO, search for new therapeutic modality against human lymphatic filariasis has emerged as thrust driven area of research considering massive socioeconomic burden associated with this disease. However, given the technical limitation of procuring parasite material from suitable animal model and huge financial burden for resource intensive in-depth research, there is need for target specific approach. Hypothesis: Available evidence suggests apoptosis as a plausible rationale, hence essential parasitic protein with potential for proliferation may be considered as prospective target. In order to achieve precision in darting them, agents with specific affinity might be exploited. In this context thermodynamic affinity between high entropy surface plasmon of nanoparticle and thiol residue of target proteins for mutual interaction may prove to be apposite. Such interaction is expected to result conformational and consequent functional derangement of the target protein. Evaluation of hypothesis: For this purpose, we have bioinformatically searched with precise criterion to retrieve essential thiol proteins from B. malayi proteome database. Further, growth associated proteins from this shortlist were selected as possible targets. Representative protein like ubiquitin C terminal hydrolase for its prominent role in cell cycle regulation, might be allowed for exposure with nanoparticle in silico, followed by authentication through real experimental evidence. Conclusion: If successful, this unique method may not only provide a valid therapeutic modality for this parasitic disease but also might develop newer insight into the physiology of parasitic growth through nano-protein interactions to be utilized in future.
PubDate: 04/09/2017 10:29:07 pm
- Oxidized LDL elicits protein disulfide isomerase reductase activity
temporally associated with respiratory burst in macrophages.
Abstract: Atherosclerosis is an inflammatory disease whose progression is strongly associated to oxidative stress. Oxidized low-density lipoprotein (ox-LDL) is thought to have a central role in atherosclerosis development, mainly due to induction of foam cell formation from its accumulation in macrophages. Despite antibodies against ox-LDL (anti-ox-LDL) has been demonstrated in human sera, there is no consensus of itssignificance. To elucidate the immunogenic implication of anti-ox-LDL production, we explored the hypothesis that, as much as ox-LDL, it elicits oxidants production via NADPH oxidase activity by inflammatory macrophages. Ox-LDL alone triggered significant superoxide anion release by macrophages (39.7±1.14 nmol/min/106 cells) compared to dormant phagocytes (1.2±0.4 nmol/min/106 cells), while complex ox-LDL/anti-ox-LDL antibodies elicited stronger NADPH oxidase activity (107±1.16 nmol/min/106 cells). Protein disulfide isomerase (PDI) has been previously shown as a chaperone involved in protein translocation of NADPH oxidase components to the phagocytic membrane surface. So, we determined its reductase activity under identical stimuli. Using a fluorescent probe cleavage, we were able to demonstrate that either free or anti-ox-LDL-bounded ox-LDL prompts a vigorous PDI thiol reductase activity, event inhibited by ditionitrobenzoic acid and bacitracin. These results suggest that ox-LDL alone or anti-ox-LDL-complexed trigger PDI activity on macrophage membrane temporally correlated to NADPH activity.
PubDate: 04/09/2017 10:29:07 pm
- Platelet-rich plasma: A novel adjuvant treatment for recurrent anterior
urethral stricture.
Abstract: Urethral stricture is one of the oldest known urologic diseases and has a substantial impact on quality of life and healthcare costs. An internal urethrotomy is any procedure that expands a stricture by incising it transurethrally. The goal of the internal urethrotomy is an enlarged lumen. However stricture recurrence is the most common complication of internal urethrotomy. Several adjuvant therapies have been used in conjunction with internal urethrotomy but none of them are used routinely due to lack of confirmative data. Platelet-rich plasma is an autologous blood product containing a high concentration of platelets that is being used for a very wide range of clinical healing applications. It also comprises a concentration of fundamental protein growth factors shown to be actively excreted by platelets to initiate wound healing. We therefore propose that the subcutaneous injection of platelet-rich plasma at the planned urethrotomy site may prevent recurrence and provide superior healing and long-term results.
PubDate: 04/09/2017 10:29:07 pm
- Iron loading: A peril in pregnancy.
Abstract: The article has been forwarded to the production team. The processing may take few weeks. Then the proof will be forwarded to the corresponding author. The final PDF and HTML files will be uploaded when the corrections to the proof are returned by the corresponding author.
PubDate: 07/28/2014 04:33:14 am
- The amplitude of heart rate oscillations is dependent on metabolic status
of sinoatrial node cells.
Abstract: The article has been forwarded to the production team. The processing may take few weeks. Then the proof will be forwarded to the corresponding author. The final PDF and HTML files will be uploaded when the corrections to the proof are returned by the corresponding author.
PubDate: 07/28/2014 04:33:14 am
- That the Shaken Baby Syndrome is based on a false subarachnoid model and
is therefore invalid.
Abstract: The article has been forwarded to the production team. The processing may take few weeks. Then the proof will be forwarded to the corresponding author. The final PDF and HTML files will be uploaded when the corrections to the proof are returned by the corresponding author.
PubDate: 07/28/2014 04:33:14 am
- The mathematics of the United States healthcare re-reform.
Abstract: The article has been forwarded to the production team. The processing may take few weeks. Then the proof will be forwarded to the corresponding author. The final PDF and HTML files will be uploaded when the corrections to the proof are returned by the corresponding author.
PubDate: 07/28/2014 04:33:14 am
- Epilepsy as a pyridoxine-dependent condition: Familial disorders of
pyridoxine metabolism.
Abstract: The article has been forwarded to the production team. The processing may take few weeks. Then the proof will be forwarded to the corresponding author. The final PDF and HTML files will be uploaded when the corrections to the proof are returned by the corresponding author.
PubDate: 07/28/2014 04:33:14 am
- Another interpretation for the geographical gradient of cancer mortality
rate.
Abstract: The article has been forwarded to the production team. The processing may take few weeks. Then the proof will be forwarded to the corresponding author. The final PDF and HTML files will be uploaded when the corrections to the proof are returned by the corresponding author.
PubDate: 07/28/2014 04:33:14 am
- Media diseases of the never-sleeping brain: Was George Orwell right'
Abstract: Introduction Modern media are instruments of a cross-linked social system. Because everyone is involved, media-associated psychological effects have arisen. Due to the bizarre effects of media-caused behaviour, authors have discussed the question of the entity of possible new- and media-associated symptoms and devised a practical way to approach this question. In summary, the question that arises is whether George Orwell’s literally-formulated hypotheses could clarify the phenomenon of media-associated diseases. Hypothesis Owing to the increasing use of new media tools, such as smartphones and handhelds, and social media networks, bizarre reports of media-associated aggressive or self-aggressive behaviour have arisen. These reports are perhaps not only a result of a permanent multitasking-use of the new media tools but also a new entity of media-associated diseases caused by the media tools themselves. Conclusion To check these implications, we propose a stepwise clinical pathway to clarify the question if the phenomenon of media-associated diseases is genuine or only an end result of the increased use of media tools.
PubDate: 04/15/2014 12:15:02 pm
- Serum protein halogenation and nitrosylation: trait of maintained
over-stimulation of blood phagocytes in sporadic Parkinson's disease.
Abstract: IntroductionHalogenative and nitrosative stress are two types of oxidative stress that have been proposed as pathogenic mechanisms in Parkinson’s disease (PD). They can be caused by over-stimulation of phagocytes.HypothesisWe hypothesize that maintained phagocyte over-stimulation leads to both halogenative and nitrosative stress in Parkinson’s disease, which are present in serum and cerebrospinal fluid of patients. These types of oxidative stress could modify proteins related to the pathogenesis of Parkinson’s disease.Testing of scientific methodsIn our lab, it has been detected the presence of halogenative stress in serum and, to a lesser extent, cerebrospinal fluid of Parkinsonian patients leading to excess of advanced oxidized protein products or AOPP. On the other hand, nitrosative stress is also present in serum and cerebrospinal fluid of patients with early PD, characterized by the selective increase of 3-nitrotyrosine proteins other than nitroalbumin and free 3-nitrotyrosine. Nitrosylation stress is accompanied by modification of the sites of nitrosylation of α-synuclein in patients with early PD, characterized by dominant nitrosylation of tyrosine 125/136 residues. Discussion Since metabolism of advanced oxidized protein products and 3-nitrotyrosine proteins has been associated to phagocytic over-stimulation, this pathological alteration could play a pathogenic role in sporadic PD. Our observations also lead to the hypothesis that serum level of advanced oxidized protein products is a prognostic marker for Parkinson’s disease duration, and these oxidized proteins could participate in neuroinflammation. Besides, the evaluation of nitrosative stress through enhanced levels of 3-nitrotyrosine proteins in serum and cerebrospinal fluid without changes in nitroalbumin, together with the profile of tyrosine nitrosylation of serum α-synuclein characterized by dominant nitrosylation of Tyr125/136 could serve for diagnosis of sporadic Parkinson’s disease. Nitro-α-synuclein is a main component of Lewy bodies, hallmarks of the disease, and serum nitro-α-synuclein could represent a pathogenic factor in PD.
PubDate: 04/15/2014 12:15:02 pm
- Neuro analysis: a neuro scientific psychiatry. Why' how' and
when'
Abstract: Why do we need neuroscientific psychiatry, how can we achieve it, and when will we know it has been achieved' Brain-related psychiatry is essential for us to know what exactly went wrong with our patients. Curative interventions are impossible before we know the etiopathology of our patients. How can we approach this daunting task' It has recently become apparent that global distributed neuronal-network brain disturbances cause psychiatric disorders, thus we need to find the correlated underlying neuronal-network disturbances of the various phenomenological manifestations of psychiatric disorders. NeuroAnalysis is the proposed approach and Clinical Brain Profiling is a concrete plan by which mental disorders can be translated into their associated brain disturbances. A concise overview explaining NeuroAnalysis is presented. Once we start eliminating mental disorders, we will know that neuroscientificpsychiatry has been attained.
PubDate: 04/15/2014 12:15:02 pm
- Delirium in medical inpatients: Adverse outcomes.
Abstract: Introduction Despite advances in understanding delirium over the past thirty years, adverse outcomes persist. We aim to review the literature pertaining to adverse outcomes, and their causes, associated with delirium in medical inpatients. Hypothesis Despite extensive research in delirium to date, delirium patients continue to suffer adverse outcomes. We offer four hypotheses as to why poor outcomes continue to be associated with delirium and propose new areas of research. Evaluation of hypotheses Delirium has been associated with institutionalization, increased length of hospital stay, cognitive and functional decline and mortality.1,2,3 Less is known, or even conjectured, in relation to the cause(s) of poor outcomes. Conclusions In the evidence gap we have proposed a number of hypotheses that explore the attrition observed in delirium. These can be understood within the dynamic tension between frailty, emergent illness, triggers, unmet need and survival properties for patients at the limits of redundancy. Further research into the drivers behind poor outcomes is needed.
PubDate: 04/15/2014 12:15:02 pm
- GATA binding protein 3: the autism perspective.
Abstract: At this moment large numbers of children in the world are suffering from the autism spectrum disorders (ASDs) while the exact etiology of this disorder is still under investigation. Even though the better diagnostic and awareness about this brain disorder is considered as reasons for the high number of subjects with ASD today, the truth of the matter, and what really matters, is that the number of children suffering from ASD are very high (about 1 in 50). Clinical interventions against ASD are currently limited and also not very rewarding. This review indicates that GATA3 may be involved in the etiology of ASD and that this molecule may be a possible drug target against ASD.
PubDate: 04/15/2014 12:15:02 pm
- Alternative view of congestive heart failure exacerbations: Role of
lymphatic function and inflammation.
Abstract: Introduction: Lymphatic function and inflammation are two related concepts that have been neglected in heart failure. All of the symptoms of heart failure, hence, compensatory mechanisms can be related to overwhelmed or dysfunctional lymphatic function. Lymphatics are responsible for tissue homeostasis controlling approximately 12 liters of fluid. These thin walled valved pumping systems are also intimately involved in immunity and control of inflammation. Lipid and nutritional transport; and repair of damaged tissues by cellular transport round out its many function. The Hypothesis: Inflammation is the cause of decompensated heart failure and lymphatics and their reaction to environment are the primary mediators. This concept is consistent with a new model of disease - regeneration balanced by degeneration with inflammation (lymphatic function) serving as the fulcrum. Evaluation of the Hypothesis: The pharmacology of lymphatic function in the context of heart failure is lacking. A new term lymphangiontrope is introduced and is defined as an intervention that improves the function of lymphatics by increasing amplitude and frequency of lymphangion contraction. A table summarizing the known pharmacological affects is presented. A table is proposed of possible therapies that could be directed toward improvement of lymphatic function allowing patients to compensate for cardiac dysfunction. Conclusion: The lymphatic system represents a peripheral therapeutic target for improving heart failure symptoms.
PubDate: 04/15/2014 12:15:02 pm
- Evolution of heart failure: Crotchety old cardiologist.
Abstract: Introduction: Diseases are in constant evolution and new diseases spring into our world. The changes can be subtle and often overlooked. The article Alternative View of Congestive Heart Failure Exacerbations Role of Lymphatic Function and Inflammationexamines the lymphatic system. This article implies that heart failure exacerbations frequently occur due to an adverse perturbation of the periphery as opposed to the decline of central cardiac function. Hypothesis: Heart failure is evolving due to environmental factors that affect the periphery. Our patients have evolved into a larger species suffering from obstructed sleep apnea, metabolic syndrome, recalcitrant hypertension, and inflammation. Right heart failure has become a more common presentation of heart failure. Evaluation of Hypothesis: Heart failure is not unique and the disease continues to evolve. Peripheral stressors include salt, systemic inflammation of diabetes and diet, obesity and obstructive sleep apnea. These environmental factors stress the right heart causing edema and fatigue. All left heart failure eventually ends in right heart dysfunction. These factors make right heart failure a significant problem that requires targeted therapy. Conclusion: Potential therapies for right heart failure are presented directing future clinical trials. The cardiologist is crotchety because he wants to know the effect of heart failure medication on circulating stem cells, inflammation, and lymphatic function a powerful mediator of peripheral compensation.
PubDate: 04/15/2014 12:15:02 pm
- Appetite hormones and hyperemesis gravidarum.
Abstract: Introduction:Hyperemesis gravidarum is described as unexplained excessive nausea and vomiting during pregnancy, leading to fluid, electrolyte imbalance, nutritional defficiency and weight loss. The Hypothesis:Appetite is affected by many factors including the hormones. There is a communication between the gastrointestinal (GI) tract, adipose tissue and appetite centers of central nervous system (CNS). These gut-brain and adipocyte-brain axis are important for appetite regulation and have both neural and humoral components. The Evaluation of Hypothesis:The gastrointestinal (GI) tract and adipose tissue are the source of important appetite-regulating hormones. They are included in energy metabolism, and have roles in modifying appetite, insulin resistance and obesity. These hormones may also have important role in etiopathogenesis of hyperemesis gravidarum and weight changes during pregnancy. Conclusion: We hypothesize that orexigenic and anorexigenic hormones might have important role in etiopathogenesis of hyperemesis gravidarum and weight changes during pregnancy. If we can prove this hypothesis, our medical approach to hyperemesis or cases with eating disorders during pregnancy would change. We would be able to provide an effective medication to these pregnant women and thus improve quality of life and prevent high health costs.
PubDate: 04/15/2014 12:15:02 pm
- Molecular refrigerators: a new approach in anti-cancer therapy.
Abstract: Introduction The temperature difference between normal and cancer cells was proven to be one of the fundamental quantities in the cancer growth. The allosteric transition is a conformational change of a protein conditioned to the binding at a specific site; in an enzyme, the two different parts can oscillate around their equilibrium state: if the temperature increases these parts increase their oscillating amplitudes, decreasing in their functionality. The Hypothesis The entropy generation approach has been used in order to evaluate the stationary conditions of tumoral cells, in relation to the transport processes. The tumoral systems can assume all the values of volume, temperature, chemical reaction rate and the time of chemical reaction, inside its stationary range of variation: outside of this range, the cancer cannot develop and dies. Evaluation of Hypothesis The control of these physical-chemical processes can be obtained by using molecular refrigerators in order to control the temperature of the cells. The aim is to maintain the temperature of a normal cell and not to allow the cell to increase it temperature up to the cancer state. The useful effect consists in obtaining conformational changes in a protein by supplying free energy on one site of the molecule, required for driving the cooling process. This thermalization is suggested as an anticancer therapy. The temperature variation is evaluated by using the entropy generation approach. Conclusion The results obtained represent a new approach to the study of the cancer and to the development of new anticancer therapy, based on molecular refrigeration.
PubDate: 04/15/2014 12:15:02 pm
- The proposed mechanisms of skeletal muscle contraction: Possible
uncertainties in the interpretation of the data.
Abstract: Introduction. The work of A.V. Hill and coworkers, of A.F. Huxley and followers, of Eisenberg and coworkers, of Lombardi and coworkers is rapidly sketched. The classical hypothesis. In the Huxley-Simmons model, the elastic element must be stretched by one dimensional fluctuations (Brownian motions) before any chemical change in state. The transition rates are made realistic by assuming that three or more attached state are necessary.. Evaluation of the classical hypothesis. Some of the concepts generally accepted in the models of muscle contraction are cast in doubt. These are: 1. the lack of consideration of the water-protein interactions; 2. the believe that viscosity is irrelevant in the economy of muscle contraction, 3. the concept of the drag stroke, 4. the significance of the Huxley-Simmons manoeuvre; 5. the possible interference of the equipment on the measurements; 6. the lack of consideration of the acceleration of the load. Conclusion. The lack of consideration of the above items may compromise the correct building of the model of muscle contraction.
PubDate: 04/15/2014 12:15:02 pm
- Cryotherapy for prophylaxis of wisdom teeth impactions'
Abstract: Not all third molars become impacted, but much pathology derives from those which are impacted. Consequently many impacted wisdom teeth demand surgical removal with resultant traumatic morbidity. Prophylaxis of impactions includes removal of teeth anterior in the arch with follow up orthodontics. Other methods have been proposed for terminating growth of third molar follicles for prophylaxis of impaction. Proposed here is a novel hypothesis which suggests cryo- therapy on developing follicles to avoid future impactions.
PubDate: 04/15/2014 12:15:02 pm
- Simultaneous pathways activation in the initiation of parturition in
humans.
Abstract: Introduction Despite of numerous studies and remarkable progress in the understanding of human reproduction the pathways by which parturition is initiated in humans remain unclear. Hypothesis Human parturition is a physiological reaction process initiated by the simultaneous activation of pro-labor inflammatory pathways in the utero-placental and cervico-vaginal domains. Evaluation of Hypothesis Progesterone control uterine quiescence by reducing myometrial responsiveness to cytokines. After anti-progestinic treatment there is infiltration of polymorphonuclear granulocytes, macrophages and mast cells into the cervix. Anatomical regionalization in labor promotion supports a strong association between inflammatory activation and onset of preterm labor. Nuclear factor κβ seems to be a modulator of these functions by regulating the expression of prostaglandins, chemokines and pro-inflammatory cytokines (PIC) involved in both term and preterm labor. In guinea pigs in late pregnancy, the cytokines interleukin (IL)-8 and IL-1 beta induced a cervical ripening morphologically similar to the antiprogestinic effect. Cervical ripening has been associated with activation of pathways, sharing a pro-inflammatory physiologic reaction that includes the inducible isoform of the nitric oxide synthase (NOS). Oxytocin seems to be the trigger for uterine contractions since there is a maximal oxytocin receptor formation concentration and gap junction formation in the myometrium in parturition. The steroids play a crucial role in controlling oxytocin receptor formation. Oxytocin is also one of the stimuli that increase uterine PG synthesis. Coupling of oxytocin receptor occupancy and PG synthetase activity in the myometrium contributes to parturition progression. The fetus may be involved in the coordination of placental estrogen production, through mechanical distention of the uterus, and through its secretion of neuro-hypophysial hormones as well as other stimulators of PG synthesis. Glucocorticoids, prostaglandins, estrogen and placental CRH are facilitators in the onset of parturition. Conclusion Human parturition is a physiological reaction process initiated by the simultaneous activation of pro-labor inflammatory pathways in the utero-placental and cervico-vaginal domains.
PubDate: 04/15/2014 12:15:02 pm
- Cancerogenic hypercycle: A new conception of cancer treatment.
Abstract: Introduction Modern theories on the carcinogenesis cannot explain the process of cancerous progression, i. e. the process of creation of new cancerous cell clones. The hypothesis The hypothesis on the cancerous hypercycle explains this process by the creation of a new form of inner-cell self-organization out of the chaos generated by disintegration and competition of the DNA and the RNA worlds. This process develops based on laws of synergetic and can be subject to computer modelling. Evaluation of hypothesis The molecular biology data confirm this hypothesis. Conclusion Computer modelling of this process will allow to detect cancer early, to elaborate new methods of its control and treatment.
PubDate: 04/15/2014 12:15:02 pm
- Do statins ameliorate radiation-induced cardiovascular toxicity'
Abstract: Introduction: Radiation therapy has long been implicated as a cause of cardiovascular morbidity and mortality with early reports of vessel injury dating back to the late 1800s. On the other hand statins are a class of drugs used to lower cholesterol levels. We aimed to evaluate whether statins ameliorate radiation-induced vessel injury by decreasing the atherosclerotic plaque formation or not. The hypotheses:We hypothesize that statins may be able to decrease the radiation-induced atherosclerotic plaques in the coronary arteries by protecting vascular endothelium and decreasing oxidative stress. Evaluation of hypotheses:The pathology and pathophysiology of coronary artery disease after radiotherapy appears to differ; however only slightly from that of coronary artery disease in the general population. Numerous studies of radiation injury show that the injury of endothelial cells is the key point in most tissues. Radiation also causes a loss of endothelial thromboresistance through the loss of thrombomodulin and increased expression of tissue factor which promote inflammatory processes. The morphologic changes associated with radiation-induced arterial disease are identical to those found in spontaneous atherosclerosis. On the other hand statins (3-hydroxy-3-methyl-glutaryl-CoAreductase (HMG-CoA reductase) inhibitors) are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Statins exhibit action beyond lipid-lowering activity in prevention of atherosclerosis the commonly used lipid-lowering compounds, statins, in addition to their effect on cholesterol, has many cholesterol-independent, vasculoprotective, so-called pleiotropic effects, many of which counteract the effects of radiation on endothelial cells. The non-lipid related effects of inhibitors of statins counteract many of the radiation-induced changes in vascular endothelium. Conclusion:We would use HMG-CoA reductase inhibitors in order to decrease radiation-induced atherosclerotic plaques in the coronary vessels. This idea would be important and has implication for future use.
PubDate: 04/15/2014 12:15:02 pm
- Might a pleasure improve anhedonia and depression'
Abstract: Anhedonia (a reduction of the ability to feel pleasure) is considered a key symptom in major depression and may influence some of its most important symptoms, such as apathy, difficulty in concentrating and maintaining attention, and gloomy mood. Various pleasurable sensations seem to be useful both in anhedonia and in depression. These pleasures are more intense than the usual daily ones, and their greater intensity could mean they can still be felt by a certain number of anhedonic individuals. Hypothesis Feeling a pleasant stimulus enhances the user’s sensitivity to subsequent rewards, so subsequent pleasures can be felt more strongly for a certain time. In this way, a pleasure strong enough to be still felt by some anhedonic individuals might reinforce their sensitivity to other rewards, enabling them to regain previously faded or lost pleasures, hence improving the anhedonia. Consequences Since many symptoms of depression could be influenced by anhedonia, ameliorating anhedonia may alleviate also these symptoms of depression.
PubDate: 04/15/2014 12:15:02 pm
- Eyestrain and progressive myopia: A minus lens induces asthenopia at the
near range by interfering with the development of the eye.
Abstract: Asthenopia, or eye strain, is often thought to be more prevalent in cases of presbyopia when performing close-up work, but it can also be induced in the myopic eye at the near range with a minus lens; and it contributes to progressive myopia. A minus lens projects the focal point from a close-up object farther behind the retina. The crystalline lens would have to “bulge” more to bring it into focus—more than how much it would normally “bulge” for near focusing. This means the ciliary muscle, which controls the shape of the crystalline lens, would have to tighten up more. If the ciliary muscle tightens up excessively, the oblique muscles would also tighten up more in response. (The oblique muscles are already tense since the eye is myopic.) The excess tension of the oblique muscles can force the sclera to elongate and thereby reducing the distance between the retina and the focal point. This alleviates some of the strain on the ciliary muscle. The crystalline lens would not have to “bulge” to its maximum—although it would still “bulge” more than how much it would normally “bulge” for near focusing. It can be demonstrated that if the eye was continuously subjected to such a condition for an extended period of time, near-point asthenopia can promote progressive myopia. Progressive myopia is the tendency for one’s myopia to become worse. It is attributed to asthenopia because more than the normally required “effort to see” was generated before a near image could be brought into focus.
PubDate: 04/15/2014 12:15:02 pm
- Geste antagoniste: Infiltration of its trigger point with Botulinum
neurotoxin type A in cervical dystonia.
Abstract: Introduction.Sensory components, as pain and the geste antagoniste (GA), are present in dystonia; GA temporarily diminishes the abnormal movement. Intramuscular botulinum neurotoxin (IM BoNT) is an efficacious treatment for cervical dystonia (CD) and also for some sensory conditions, such as postherpetic neuralgia and diabetic neuropathy. Hypothesis. This work tried to assess whether subcutaneous BoNT (SCBoNT), applied at the trigger point of GA, could increase the efficacy of IMBoNT in CD. Evaluation of Hypothesis. Nine patients with CD and an identified a GA were recruited. While receiving IMBoNT, five of them had no dystonia while sitting, and four had improved dystonia; seven experienced pain. In addition to the dose of IMBoNT, every patient received SCBoNT at the trigger point of GA, during eight to twenty-four months. During this period, among the five patients without dystonia at rest, one reported disappearance of torticollis during gait, and three saw the interval between IMBoNT prolonged by four or six weeks. Among four with persistent dystonia, one attained a normal neck position, and two experienced amelioration of dystonia. Pain was diminished in five patients. Conclusion.SCBoNT infiltration of the trigger point resulted in additional benefit in seven out of nine patients treated with IMBoNT. SC BoNT at the trigger point of GA might constitute a means of improving CD by itself, or of increasing the benefit provided by IM BoNT or other therapies. Further studies are needed to confirm this hypothesis.
PubDate: 04/15/2014 12:15:02 pm
- Diacutaneous fibrolysis versus passive stretching after articular
immobilization: Muscle recovery and extracellular matrix remodelling.
Abstract: Introduction: Atrophy and muscle shortening due to articular immobilization are commom problems in musculoskeletal rehabilitation. Muscle stretching mechanical stimuli might be considered as golden standard procedure to improve muscle flexibility in rehabilitation. Muscle stretching generates mechanotransduction, potentiating specific gene expression and promotes sarcomerogenesis and extracellular matrix remodeling on shortened and atrophied muscles. Hipothesis: Diacutaneous Fibrolysis- like stretching - uses an external force to stress mechanically connective and muscle tissues to treat muscle shortening; thus, it is widely used in clinical practice even if there is no evidence to support it. Considering this subject, we hypothesize that diacutaneous fibrolysis can generate mechanotransduction, affecting muscle hypertrophy and extracellular matrix remodeling after immobilization. Testing of scientific methods: Was designed a laboratory experimental study with a sample of 50 rats. The sample will be randomly divided into 5 groups: Control group (CG, n=10) with non-immobilized rats; 3-week immobilization group (IG3, n=10); 3-week immobilization/3-week non-immobilization group (INIG3, n=10); 3-week immobilization/3-week stretching group (STR, n=10); and 3-week immobilization/3-week Diacutaneous Fibrolysis group (DF, n=10).All rats will have their left tibiotarsal joint immobilized in maximum plantar flexion with the orthotics for 3 consecutive weeks. After the immobilization period the intervention groups will receive their respective intervention on their left triceps suralis for 3 weeks. The dependent variables of the study will be: sarcomere analysis, polymerase chain reaction, conective tissue density, collagen birefrigence and matrix metalloproteinases. Statistical analysis will be performed using analysis of variance and Duncan post hoc test will be applied for differences between groups. For all calculations a 5% (p<0,05) significance level will be established. Discussion: If the hypothesis is confirmed, the present study might provide evidence to support the use of this physical therapy resource widely used to treat muscle dysfunctions.
PubDate: 04/15/2014 12:15:02 pm
- Could wisdom tooth provide tooth germs for tooth regeneration'
Abstract: To completely regenerate a tooth in human oral cavity is not yet achieved by current studies. Here we conceive a man-induced method to construct a teeth germ and that might be used to regenerate a tooth in vivo. This idea generated by traits of the development of the compound odontoma, a benign tumor of tooth malformation. The disease is a kind of developmental tooth malformation, characterized by several small teeth inside the entity. Those scattered denticles/daughter teeth germs, formed in early stage of odontoma morphogenesis, showed similar layers with normal tooth, and could grow into tooth-like shapes. In consideration with recent report that mouse tooth germ constructed in vitro could develop into a fully functioned tooth in adult mouse jaws. We hope this hypothesis could help to generate tooth germs for in vivo implantation.
PubDate: 04/15/2014 12:15:02 pm
- BID is a potential link between DNA damage and inflammatory responses in
tumorigenesis.
Abstract: Introduction The BH3-only BID is a pro-apoptotic protein of the Bcl-2 family that is crucial for mitochondria-mediated apoptosis in many cell systems. However, some recent studies find that BID may also play a pro-survival role. It can be the intermediate substance of DNA damage response, which is connected with the phosphorylation of BID.Likewise, BID-/- cells and mice decrease the release of inflammatory factors. BID is also a mediator of inflammation. Hypothesis Based on the above point of view, we hypothesize that BID,a novel convergent molecular, is a potential link between the inflammation and the irrepairable DNA damage responses in tumorigenesis. Evaluation of hypothesis Clear evidence has been obtained that inflammation plays a critical role in tumorigenesis, and some of the molecular mechanisms have been elucidated including the inflammation in tumorigenesis is related to the DNA damage. The inflammatory cells turn into cancer cells that their DNA must be destroyed. Most of the time, damaged DNA is able to be repaired, and BID phosphorylation by the kinase ATM involved in the DNA repair response. But if over the ability, the damaged DNA will initiate the cells or the organs apoptosis or tumorigenesis. Moreover, BID drives production of pro-inflammation cytokine and chemokines resulting in either increasing of stressed cells or a local inflammatory response. So, we consider that inflammation depends on BID to link DNA damage response. Conclusion BID plays a key regulatory role in boththe inflammation and DNA damage responses. However, the acting forms are difference, and the works time may same or either. In brief, BID,a novel convergent molecular, may be a potential link between the inflammation and the irrepairable DNA damage responses in tumorigenesis. However, much more works needs to be done to demonstrate the hypothesis.
PubDate: 04/15/2014 12:15:02 pm
- IgG4-associated complement activation in membranous nephropathy - a Fab
phenomenon'
Abstract: IgG4-related diseases encompass a growing list of organ involvement including membranous nephropathy, a disease entity generally associated with circulating antibodies to glomerular antigens and localized activation of complements. Although both IgG4 and complements were present in the renal biopsy specimens, the mechanistic link between them remains uncertain, particularly since IgG4 is known to inhibit complement activation. The solution to this conundrum may lie in the recently discovered Fab arm exchange phenomenon. In this article we hypothesize that IgG4 molecules undergo structural perturbations via the dynamic Fab arm exchange phenomenon, which might then render it capable of complement activation and hence have a direct role in the pathogenesis of IgG4-related MN.
PubDate: 04/15/2014 12:15:02 pm
- Vasa vasorum hypoxia in arteriosclerosis obliterans, peripheral artery
disease and restless leg syndrome.
Abstract: Introduction With the ageing population circulation problems in the peripheral arteries decrease the quality of life. ASO (arteriosclerosis obliterans), PAD (peripheral artery disease), IC (intermittent claudication) and RLS (restless legs syndrome) are the main diseases associated with problems of the peripheral arteries. They cause unpleasant sensations all over the body. The vasa vasorum (v.v.) consist of the internal and external part and form a microvasculature of the arterial walls. The sympathetic nervous system releases noradrenaline (norepinephrine) directly into the blood and consequently from v.v. into the outer layer of smooth muscle cells starting their contraction5. The contraction is maintained by the stretching. The hypothesis We propose two pathways for the pathophysiology of ASO, PAD and RLS: 1. A new microvascular hypoxia hypothesis and 2. A sympathetic pathway via noradrenaline (NA). However, both pathways lead to an increasing hypoxia of the main arterial wall and finally to the diseases. We propose that the most vulnerable part of vasculature is v.v.. A minor arterial constriction leads to a significant decrease in blood flow in v.v. and, thus, to a hypoxia and finally anoxia (Fig.1). Simultaneously, smooth muscle cells in hypoxia cannot relax due to a lack of ATP and the blood flow in the main artery is impaired. Therefore these diseases could be classified as microvascular diseases. Evaluation of Hypothesis Based on the anatomy and physiology, it is obvious that oxygen supply via vasa vasorum is the evolutionary weak part of the circulation due to theit branching and low blood pressure against the high intramural pressure in the layer of the smooth muscle. Conclusion We propose an simple explanation for several vascular diseases. Their origin might be in the structural and functional weaknesses of the v.v., which lead to metabolic problems, hypoxia, in the smooth muscle layer of the main artery.
PubDate: 04/15/2014 12:15:02 pm
- Quantitative urinary biomarkers of epilepsy as a pyridoxine-dependent
condition.
Abstract: The study testifies hypothesis on epilepsy as an inborn error of pyridoxine (vitamin B6) metabolism and suggests non-invasive quantitative biomarkers for evaluation of clinical status and monitoring an individual treatment by antiepileptic drugs. In children with different forms of epilepsy and matched healthy controls urinary parameters of pyridoxal-phosphate (PLP)-dependent tryptophan degradation were measured by HPLC method with simultaneous ultraviolet and fluorimetric detection. Concentrations of compounds formed or metabolized in the course of tryptophan degradation (kynurenines, indoxyl-sulfate) and correlations between them turned out to be quantitative biomarkers useful for evaluation of patient’s clinical state and monitoring individualized antiepileptic treatment. In particular, the value of 4-pyridoxic acid to kynurenine ratio appears to be an index of an experienced seizure attack, while the ratio of 3-hydroxyanthranilic acid to 3-hydroxykynurenine reflects activity of kynureninase, the enzyme of critical sensitivity to PLP supply. Growing progressively worse, epilepsy is accompanied by aggravation of PLP-dependent disturbances of tryptophan metabolism and expanding inhibition of kynureninase. The affected pyridoxine metabolism is discussed as an inborn genetic sign of epilepsy open to many years of pyridoxine replacement therapy.
PubDate: 04/15/2014 12:15:02 pm
- Do we need new HbA1c target'
Abstract: HbA1c should be tested during the first and subsequent assessments in all diabetic patients since HbA1c reflects mean glycemia over the past few months and has a strong predictive value for diabetic complications. Studies have shown that tight blood glucose control reduces complications in diabetic patients. The most important limiting factor for tight blood glucose control is hypoglycemia. However, it is known that incretins (GLP-1 analogues and DPP-4 inhibitors), that have been increasingly used, do not cause severe hypoglycemia.
PubDate: 04/15/2014 12:15:02 pm
- Tears shedding may be adapted to heal physical and psychological hurting
in man.
Abstract: In addition to human many other animal species shed tears. Theories suggest that tears serve as a pain response, sympathies gainer, and nonverbal communicator as pheromones, stress and toxin releaser and way of expression of sudden intense emotions. However, these theories remained partially acceptable and the question is still alive that why we shed tears on getting mental or physical injuries' As for basal tears are for lubrication of eyes, nostril damping and eye protection is acceptable but shedding emotional tears seems to a mere wastage of such important proteins and electrolytes. Therefore, we gave hypotheses about the usefulness of tears shedding adaptation in man that tears shedding are to heal the physical injury as they contain antimicrobial, tissue healer and analgesic products and the components of tears must be reflected in high concentration in nervous system and somatic systems on psychological hurting; therefore tear may act as mental healer. In order to assess antimicrobial activity, the diameters of zones of inhibition by human emotional tears applied on bacterial cultures and a broad spectrum antibiotic (positive control) will be measured and compared. Skin wounds of equal thickness and deepness will be created on the back of animals. Microscopic morphological characteristics of wound healing will be compared in wounds treated with tears (experimental) and treated with sterile saline (control) groups. Moreover, pain will be assessed and compared in control and experimental animals. Protein analysis will be done in tears and cerebrospinal fluid by using standard protocol to find out quantities of tears specific proteins and correlate with their tears. Tears being antimicrobial, tissue healer and analgesic may have some usefulness in them and tear shedding may be a useful adaptation in man.
PubDate: 04/15/2014 12:15:02 pm
- Enhancing safety and efficacy of bisphosphonate therapy by association
with hydroxyapatite as adjuvant drug carriers.
Abstract: Osteoporosis or decay of bones is one of the major causes of morbidity and sometimes mortality across the world. An enhanced bone resorption and decreased bone regeneration could be the reasons underlying this disease. Bisphosphonates are one of the most potent treatment strategies available for the treatment of this condition. Bisphosphonates negatively influence the bone resorption activity by decreasing osteoclast survival. However, they are associated with a wide number of side effects which might be associated with the molecular mechanism of their action. A simultaneous use of hydroxyapatite which acts by a divergent mechanism i.e. osteoinduction and osteogenesis may however potentiate the action of bisphosphonates with reduced side effects. Furthermore, hydroxyapatite offers distinguish advantage of getting converted to different drug carrier such as ceramic based nanoparticles. Hence, bisphosphonates delivered by a hydroxyapatite based drug carrier may have a potentiating effect of bisphosphonate action with reduced side effects.
PubDate: 04/15/2014 12:15:02 pm
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