Journal of Medical Hypotheses and Ideas
Volume:2 Issue: 2, 2008

Efficient non-viral vectors for gene delivery based on chitosan polymer is dependent on a variety of factors, e.g. loading and lelease capacity, stability in biological system and complex size. This system may have low loading, release and stability capacity. Biodegradable and biocompatible nanoparticles formulated using a chitosan polymer has the potential for sustained and controlled gene delivery. Our hypothesis is that nanoparticles-mediated wild-type p53 gene delivery would result in sustained gene expression, and hence better efficacy with a therapeutic gene. In this study, we have determined the pharmaceutical and biological characterization of Chitosan nanoparticles containing wild-type p53. Nanoparticles containing plasmid were formulated using a microemulsion reverse micellar and ionic gelation techniques. In conclusion, chitosan nanoparticles- p53 complex gene delivery results in sustained and better antiproliferative activity, which could be therapeutically beneficial in cancer treatment.

A variety of options is available for retinal detachment (RD) repair, including pneumatic retinopexy, scleral buckling and vitrectomy alone or in combination with a scleral buckle. However, RD-induced photoreceptor degeneration causes permanent loss of visual performance even after successful surgery. The increased expression and release of tumor necrosis factor-α (TNF-α) is an important cause of photoreceptor degeneration associated with RD. It also plays an important role in proliferative vitreoretinopathy (PVR) formation. Therefore, we propose that systemic or intravitreal use of infliximab (an anti-TNF-α monoclonal antibody) in adjunct with standard RD surgery may halt the process of photoreceptor degeneration and prevent PVR formation, which would enhance the anatomic and functional outcome of RD surgery.

Spatial resolution of the eye is determined in the complex pattern and all the layers of the retina as well as the primary visual cortex and lateral geniculate body contribute. There is evidence that any given pathway transmitting visual information is restricted to a limited band of spatial frequencies. Moreover, it seems that the limiting array is in the retina. More than a century ago, Bergmann and Helmholtz laid the foundation for the sampling theory of visual resolution when they argued that for two points to be discriminated, at least one unstimulated photoreceptor must lie between two stimulated photoreceptors. In this article, we propose that the photoreceptor diameter is not the limiting factor for spatial resolution, and contrast sensitivity is the end-point determinant factor in the spatial frequencies less than photoreceptor diameter.

We have previously shown that rose bengal (RB) itself and not as a photosensitiser could induces dual modes of cell death in melanoma cells and has clinical activity against melanoma. But the mechanisms of RB-induced cell death are unclear. Recently lysosome was reported to initiate different kinds of cell death including necrosis, caspase-dependent and -independent apoptosis. The hypothesis of this study is to investigate the role of lysosome in mediating RB-induced cell death in melanoma cells focusing on lysosomal protease cathepsin B (CB). We present two lines of evidence indicating a central role for the CB in mediating cell death. First, inhibition of CB would result in a strong protection against drug-induced cell death and apoptosis in melanoma cells. Simultaneous inhibition of caspases would determine that CB acts upstream or downstream the caspase cascade. Second, we show RB triggers disruption of lysosomes leading to release and activation of CB using an engineered yellow fluorescent protein-tagged CB. It is hypothesized that RB-induced cell death in melanoma cells is mediated through lysosomal CB in this novel cell death pathway. This idea points to a new tumor-suppressive role for lysosomes which may be less affected by chemotherapy-induced resistance mechanisms.

difference in the sedimentation of red blood cells from healthy and non-healthy ones can be seen. To support a previously published work on the idea that red blood cell inclusion could increase of erythrocyte sedimentation rate (ESR). The author hereby studied the ESR in the malarial infection model. It could be seen that ESR is increased in malarial infection and varies on the intensity of infection.

Many studies have indicated that viruses can interact with mitochondria and affect their function. Further, emerging data now show that many more viruses may influence the mitochondrial pathway of apoptosis and thus there is widespread potential for interaction with the respiratory chain in this organelle. Such interactions could have consequences for the clinical outcome of persistent viral infections when energy generation is disturbed; and eventually will be a possible cause for chronic fatigue syndrome (CFS). Therefore, it is hypothesized that viral infections maybe the main aetiology for this syndrome.

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders characterized by predominantly macrovesicular hepatic steatosis that occur in individuals even in the absence of consumption of alcohol in amounts considered harmful to the liver. At present, there is no standard recommended treatment for NAFLD. Treatment currently focuses on gradual weight loss through diet and regular exercise. Insulin sensitizers such as thiazolidinediones and metformin show promise, and several studies have explored the role of lipid lowering agents and antioxidants. Coenzyme Q10 (CoQ) is a powerful antioxidant and has an important role in respiratory metabolism, as a mobile electron and proton carrier in the mitochondrial electron transport chain. However, to date, there is no published clinical trial on CoQ in NAFLD. We postulate the hypothesis that CoQ might be effective in the treatment of NAFLD.

Patients with zonular weakness, undergoing cataract surgery, have a very high risk of the Intraocular Lens (IOL) dislocation during this operation. Strengthening the capsular bag is undeniably important in these patients. In this article, we suggest a novel surgical technique as a prospective treatment for zonular weakness in such patients. A triangular capsular flap is cut from the anterior capsule with the base directed towards the zonular break area. Basal peripheral iridotomy (PI) is performed in the same zone through corneal paracentesis. The tip of the capsular flap is caught with capsular forcept which is guided through both PI and corneal paracentesis. The tip of the flap is fixed in corneal stroma with a full thickness 10/O suture. After the lens implantation, the triangular anterior capsular flap is sutured in PIat iris edges and residues of flap in the anterior chamber are cut along the iris plane. Sutures from cornea along with the cut part of the flap are removed. This technique may be more practical in ECCE but it is very difficult to perform in Phacoemulsification. In this condition, a very tiny iris clip can be used instead of suturing to grasp the capsular flap in PI site and suspend it from the iris. This flap prevents dislocation of bag contents into vitreous and the possibility of vitreous loss through zonular defect and is a reliable support for PC/IOL. We can perform zonuloplasty in one quadrant zonal defect or 2-4 quadrants in the cases like Marfan Syndrome. Zonuloplasty is an innovative surgical procedure in cases with zonular instability more than 1/4 quadrant when CTR is ineffective.

Multiple sclerosis (MS) is widely believed to be an autoimmune disorder. Another exciting idea regarding the aetiology of MS may be that the immune response in MS could result from a chronic infection rather than autoimmunity in the usual sense. M. leprae-induced myelin damage in the early infectious process provides valuable insights into the pathologic mechanisms of multiple sclerosis. However, no research has hypothesized the possible involvement of mycobacterium leprae or its components in pathogenesis of MS. Most of the antigens of mycobacterium leprae and mycobacterium tuberculosis are members of stress protein families. Of the M. leprae and M. tuberculosis antigens identified by monoclonal antibodies, all except the 18-kDa M. leprae antigen and the 19-kDa M. tuberculosis antigen are strongly coded with very similar genes. I hypothesize that MS is a syndrome of diseases, induced by intradermal BCG vaccine which may contain the antigen component resembling that of leprae that can either produce central demyelination by itself, or by delayed hypersensitivity. The hypothesis should be assessed in several experimental and clinical trials. If my hypothesis can be verified experimentally and clinically, then measurements to prevent MS disease could be accomplished.

Orbital lymphangiomas are non encapsulated tumors and one of the most common vascular tumors in children. Surgery indicated for selected patients but complete resection of tumors is difficult due to their diffuse infiltration within adjacent tissues. Carbon dioxide, contact Nd:YAG lasers and percutaneous sclerotherapy as an alternative to surgical resection have variable success. Challenge continues to be to find a safe and effective therapeutic modality for this purpose. There are many data supporting a casual role for vascular endothelial growth factor (VEGF) in lymphangiogenesis. One possible strategy for treating orbital lymphangioma is to inhibit VEGF activity by competitively binding VEGF with a specific neutralizing anti-VEGF antibody. The vitreo-retinal service in the recent years enjoyed a high level of success in managing diabetic retinopathy, choroidal neovascularization, and neovascular glaucoma using anti-VEGF strategies. Efficacy and tolerability have been demonstrated for drugs targeting VEGF. We herein hypothesize that intralesional application of anti-VEGF agents such as pegaptanib, ranibizumab and bevacizumab are potentially useful for treating orbital lymphangioma and preventing its complications. Further investigations are needed to place this mode of treatment alongside orbital lymphangioma therapeutics.

When advanced biliary or pancreatic malignancies preclude application of surgery or stent placement for relief of jaundice, the remaining option is percutaneous transhepatic biliary drainage (PTBD). However, it is associated with problems such as loss of biliary fluid and minerals, malabsorption of fat, and discomfort. A new surgical method for palliative biliary drainage in malignant obstructive jaundice consists of connection of PTBD catheter to a jejunostomy catheter. With this configuration, external drainage converts to internal drainage type. This is a safe method with minimal morbidities and several advantages. It will improve the patient's quality of life, minimize loss of fluid and electrolytes and permit normal enterohepatic circulation.

Intravitreal injection is the common method for treatment of the posterior segment eye diseases. The advantage of intravitreal injection is achieving the desired concentration of drug inside the eye and reduction of drug side effects. Unfortunately, repeated intravitreal injections can cause several ocular complications including; vitreous hemorrhage, endophthalmitis, retinal detachment and cataract. For this reason, it seems the usage of sustained release drug delivery systems is helpful. Bevacizumab (Avastin®), antivascular endothelial growth factor (VEGF) monoclonal antibody, is used for the treatment of different ocular diseases such as neovascular age-related macular degeneration, neovascular glaucoma, diabetic retinopathy, retinal vein occlusions, etc. For reduction of drug side effects and improvement of drug half-life after intravitreal administration, we suggest preparation of liposomal bevacizumab as novel drug delivery system and comparison of this new formulation with conventional formulation in the market.

Intra-abdominal adhesions are the most common cause of small bowel obstruction. Infertility in women and chronic abdominal-pelvic pain are the other problems of adhesiogenesis which impose a great economic burden on the population health. On the other hand, increased levels of transforming growth factor beta1 (TGF-β) are shown to play a role in formation of adhesion bands and can impair peritoneal fibrinolysis. Moreover, simvastatin, an immunomodulator agent, can down-regulate TGF-β. Although it is shown in previous studies that simvastatin antagonizes the interaction between TGF-β and connective tissue growth factor (CTGF), no human study exists on the effect of simvastatin on surgical adhesion band formation. We hypothesize that simvastatin, through its effect on reducing the level of TGF-β, may be useful in preventing adhesion band formation after surgical procedures. Surely, this hypothesis should be assessed in several experimental and clinical trials.

Foot ulcers are common in 12-25 percent of diabetic patients. Preventing, controlling and treating of these kind chronic wounds are of the major clinical challenges.Evidence based documents revealed that DFU (Diabetic Foot ulcer) is a chronic wound type originating from disturbed cellular and molecular mechanisms that have to be in its functional form to overcome its problem. In diabetes and some other chronic based diseases, harmonized acting machine causes chronic phases that result in conditions as foot ulceration and related complications seen commonly in diabetes.DFU needs to be transformed into acute phase in order to be healed in a physiological manner. Disturbed mechanisms have to be corrected reversely and to achieve such a goal it is essential to better understanding of disturbing factors responsible for biological abnormalities. Factors associated with DFU are as cellular and molecular recruitment and function impairments and there is need to repair these mechanisms. For this, we believe that the activated Th-1 cells (T helper-1 Cells) might have a critical role in regulation of the several effector functions of the cellular and molecular mechanisms essential to the body to act the best. Evidences and our successful results urge us to suggest this regulatory role for effector cells and molecules generated through activation of Th-1 cells as a treatment strategy.

Erythrocyte sedimentation rate is an important laboratory test in hematology. Inclusion body is an abnormal addition within red blood cell that can occur in cases of many abnormalities. Inclusion body is an object and has mass therefore, it poses its specific weight which can modify the normal sedimentation of red blood cell. Here, the author proposed the mechanism that reduce the erythrocyte sedimentation rate in splenectomized thalassemia and further imply for other conditions with inclusion body in red blood cell. It can demonstrate that the increase of additional mass due to inclusion body can reduce the time for sedimentation.

Syphilis is a well-known sexually transmitted disease found around the world. Malaria and syphilis are endemic in many regions of the world, and co-infection with the two pathogens is common. Here, the author used a new pathway ontology technology to predict the pathway of CD4+ suppression in an episode of co-infection. Of interest, the author found that there are some immune suppression process that can be found both in syphilis and malaria. The mentioned processes are inhibiting interleukin-2 secreted by CD4+ and nitric oxide production. In the co-infection, the synergy to increase the immune suppression can be expected.

Orbital lymphangiomas are non encapsulated tumors and one of the most common vascular tumors in children. Surgery indicated for selected patients but complete resection of tumors is difficult due to their diffuse infiltration within adjacent tissues. Carbon dioxide, contact Nd:YAG lasers and percutaneous sclerotherapy as an alternative to surgical resection have variable success. Challenge continues to be to find a safe and effective therapeutic modality for this purpose. There are many data supporting a casual role for vascular endothelial growth factor (VEGF) in lymphangiogenesis. One possible strategy for treating orbital lymphangioma is to inhibit VEGF activity by competitively binding VEGF with a specific neutralizing anti-VEGF antibody. The vitreo-retinal service in the recent years enjoyed a high level of success in managing diabetic retinopathy, choroidal neovascularization, and neovascular glaucoma using anti-VEGF strategies. Efficacy and tolerability have been demonstrated for drugs targeting VEGF. We herein hypothesize that intralesional application of anti-VEGF agents such as pegaptanib, ranibizumab and bevacizumab are potentially useful for treating orbital lymphangioma and preventing its complications. Further investigations are needed to place this mode of treatment alongside orbital lymphangioma therapeutics.

Increased oxidative stress and disturbed glutathione redox system play an important role in the pathogenesis of human immunodeficiency virus (HIV) infection. Depletion in intracellular levels of reduced glutathione (GSH) contributes to an increment in tumor necrosis factor α (TNF-α)-stimulated-HIV-1-transcription, activation of HIV-1-replication, sensitivity to TNF-α-induced cell death, and impairment of CD4+ cell function and survival. Therefore, several studies have investigated the effect of GSH-enhancer agents such as N-acetyl cystein in the treatment of patients with HIV infection. With regard to the beneficial effects of Angelica sinensis, a Chinese medicinal herb, on GSH redox system and the pathogenic role of GSH depletion in HIV infection and the immunomodulator effects of active ingredients of this herb, we postulated that Angelica sinensis may be of value in the treatment of HIV-infected patients.

Pancreas islet transplantation is one of the potential cure for type 1 diabetes. However Current isolation techniques lead to loss of number and function of isolated islets during procedure, needing in any cases two donors for each transplant. To overcome this problem many factors and added extra protocols should be investigated during isolation process. Low level laser irradiation (LLLI) is currently being used to treat wide variety of medical conditions. Many studies have proved cellular proliferation after in-vitro irradiation of low level laser. Effects of LLLI in secretory cells have been also considered. It has been shown that products of these cells are amplified after irradiation. These effects on LLLI are explained by increasing intracellular ATP and Ca2+ flux. Based on these findings, it can be hypothesized that low level laser could be beneficial for islet viability and function, if it irradiates to islets during isolation procedure.

Nerve growth factor (NGF) is the founder-member of neurotrophins family that provides growth and surviving effect not only for neuronal tissue but also for various non-neuronal cellular populations. It effectuates its physiologic or pathologic functions in sensorial neuronal system and some certain tissues through NGF-receptors such as tyrosinkinase A and p75, involving also transient receptor potential vanilloid 1, substance P and its receptor NK1 (members of NGF-pathways - NGFP). In different situations, such as stress-related or inflammatory pathologies (including allergy, asthma, depression, multiple chemical sensivity, stressful or dangerous events, etc), are reported elevated local and serologic concentrations of these mediators.Reflecting on the pleiotropic effects of mentioned substances, it could be suggested that over-regulation of NGFP mediators is generally required during identification of somatic or psycho-emotional integrity threatening like a surviving proclaim. In this context, the identification of a danger may induce NGFP-mediated growth stimuli to assure better surviving possibilities for the organism, maybe as a compensatory effect. Experiments in knockout animals with regards to genes of NGFP mediators could be helpful for the verification of its role as leader of information in the mentioned processes. Some investigations in such animals have demonstrated their abnormal passivity to fight for vital demands, whereas the behavior of subjects with down-regulation of aforementioned factors is associated with sensory or cognitive disorders such as congenital insensivity for pain with anhidrosis, schizophrenia, diabetes, or self-mutilatory behaviors. The last mentioned facts manifest the inability to recognize the situation of bodily and mental integrity during the NGFP insufficiency, leading to the necessity for further pharmacologic investigations with regards to NGFP mediators in the related pathologies.

Vernal keratoconjunctivitis is a chronic, recurrent and severe ocular allergic disease, which is characterized by persistent allergic inflammation of the conjunctiva. It can be accompanied by ocular discomfort and visual disturbance. All forms are characterized by intense itching, tearing, mucous secretions and a severe photophobia, which often forces children to live virtually in dark places. Conjunctival proliferative changes, such as the formation of giant papillae are the characteristic findings of affected individuals. Giant papillae develop as a result of infiltration of inflammatory cells, changes in the epithelial layer, and increased deposition of extracellular matrix molecules such as collagen and proliferation of conjunctival fibroblasts. Currently several therapeutic options such as corticosteroids, mast cell stabilizers and cyclosporine are applied for treatment of Vernal keratoconjunctivitis, but in long-term, the chronic and recurrent nature of this problem leads to failure or appearance of side effects of current treatment in many patients. Recently, Green tea extract and its principal active ingredient, epigallocatechin gallate, are gaining attention and increased usage due to its healthful properties. It has considerable anticatactogenic effect by inducing apoptosis in lens epithelial cells and antioxidant effects. Also its great benefits were achieved in attenuation of damaging influences to the retina caused by ischemia/reperfusion. Based on evidences supported beneficial effects of green tea, we hypothesize that local administration of green tea and its extract seems to be a proper substitute or adjunct to current treatments of Vernal keratoconjunctivitis. This plant contains a series of antioxidants that can abolish the process of allergic cascade. Moreover, by suppressing TNF-alpha potentially, it can reduce proinflammatory reaction, as well as fibroblast proliferation and subsequently decrease giant papilla formation; however, its potency should be evaluated in multiple clinical trial studies.

Malarial infection in red blood cell disorder is an interesting topic in tropical medicine. In this work, the author proposes a new idea on the physical property of red blood cell and risk for getting malarial infection. The study on scenario of red blood cell disorders is performed. Conclusively, the author found that physical property of red blood cell is an important determinant for getting malarial infection