therapeutic

Background: Corneal abrasions are a common result of eye trauma. Corneal injuries are very common in both the adult and pediatric population and account for a significant proportion of the workload of most emergency departments. Although abrasion heals well with preservative treatment, it still causes pain and job lost. The abrasion result from the scrabble of the corneal epithelium. These injuries cause pain, tearing, lids spasm, light scare, foreign body sensation, decreased visual acuity/blurring, and a gritty feeling. The light, friction & wink was worse the condition. Most abrasion cure within 24-27 hours and seldom proceed to erosion or infection. The study aims to use bandage soft contact lens [BSCL] as a primary treatment for traumatic corneal abrasion [TCA] instead of traditionally use pressure patch [PP]. Patients and methods: The present prospective study has been conducted on 50 patients attending the out-patient department of ophthalmology in an Alyarmouk teaching hospital for six months after taking ethical permission. Before subjecting the patient to the treatment of bandage soft contact lens therapy, a detailed clinical history and thorough local examination have been done. A history indicating the occurrence of recent ocular trauma followed by severe pain, redness, lids spasm, photophobia, and tearing of the involved eye is suggestive of a corneal abrasion. Always we ask about contact lens wear as this can complicate the presence of an abrasion. To confirm the diagnosis of traumatic corneal abrasion we examine the cornea by slit-lamp under cobalt-blue filtered light after the application of tetracaine eye drops & fluorescein strips. The treatment of 50 consecutive patients presenting with traumatic corneal abrasion has been treated with anesthetic eye drop (tetracaine 0.5%) to relieve pain and lids spasm, antibiotic eye drop (ofloxacin 0.3%), therapeutic bandage soft contact lens was applied to provide pain relief and once again act as a splint to promote epithelial healing, then visual acuity was measured by Snellen chart, a cycloplegic eye drop (cyclopentolate 1%) was applied to relieve ciliary spasm & then preservative-free lubricant eye drop were applied lastly. This criterion dramatically relieves most, if not all of the pain the patient may be experiencing (which is a big plus for the patient and earns instantaneous trust), but it also allows the patient to return to work/school or any other daily activities. Patients have been evaluated after 24hours, 72hours and after 1week regarding pain, visual acuity, and complications. Though pressure patch [PP] occasionally advice in abrasion therapy, it does not assist and may prevent recovery. Employ the protective eyewear can preclude the traumatic corneal abrasion. Results: A total of 50 cases were enrolled in our study during the study period of 6 months. Out of 50 patients, there were 30males and 20 females and the male/female ratio was 3:2. The patient’s age was ranged from 5-35years. The commonest cause of injury was direct minor trauma (80% of cases), with cosmetic & optical contact lenses related problems accounting for 20% of presentations, visual acuity was documented correctly in 90% of adult and pediatric group and difficult to documented in children less than 6-year-old 10%. Traumatic corneal abrasion treated with bandage soft contact lens has an apparent advantage over the traditional pressure patch in terms of reduced pain, speedier healing, and an advantage of faster rehabilitation, facilitation epithelial healing, and proper surface hydration. Evaluation of pain revealed sufficient comfort with this regimen, allowing 45 patients (90%) to go back immediately to their occupations. Moreover, visual function is retained without any complication. Healing of the traumatic corneal abrasion occurred within 1 to 3 days in all patients, with minimal or no pain. The infection did not occur at the time of the follow up. We remove the bandage soft contact lens after 1 week to allow epithelial migration and attachment without the interference of the shearing forces of the upper lid. Conclusion: The use of bandage soft contact lens as a primary treatment for a traumatic corneal abrasion is a safe and effective method with anesthetic eye drop (tetracaine 0.5%), antibiotic eye drop (ofloxacin 0. 3%), cycloplegic eye drop (cyclopentolate 1%), preservative-free lubricant drop instead of traditionally pressure patch. Bandage soft contact lens causes dramatic improvement from pain, lid spasm, tearing & visual function is retained without any complication, and patients can immediately resume their regular activities.

Background: The present study was conducted to study the donor profile and to assess the trends of cornea donation. Methodology: This was conducted as a hospital based cross sectional study at a tertiary care centre in Central India for a period of 5 years. Data was retrieved from 70 patients from eye bank who filled form of eye donation at Eye bank of our institution. Sociodemographic profile of donors, cause of death and time since death was recorded. Source of information regarding corneal donation and reason for not willing to donate the cornea for research purpose was recorded from the filled form. Further cornea enucleated were subjected to serology and their utilization for various purposes were recorded in questionnaire. Results: The present study retrieved data from a total of 70 donor forms with mean age of 65.84 ± 18.4 years. Cornea obtained from younger patients were mainly utilized for corneal transplantation whereas that from elderly age group > 60 years were mainly utilized for research/training purpose and the observed difference was statistically significant (p < 0.01). The corneas retrieved and utilized immediately after death were significantly used for optical or therapeutic purposes (p < 0.05). Conclusion: The present highlights the donor profile and trends of corneal donation at the tertiary care facility of Central India. It was observed that though the younger population and older population both are aware regarding corneal donation but still they are less aware on purpose for which cornea can be utilized. Quality of donor cornea is better when death to enucleation time interval was less.

Fungi cause a variety of diseases and are difficult to treat owing to their eukaryotic nature resulting in dearth of antifungal targets at hand. This problem is further elevated many folds due to the resistance mechanisms of fungi through which they circumvent the antifungal drugs administered for therapeutic purposes. Fungi have a variety of strategies for obtaining these resistances, amongst them pivotal role is played by the ABC and MFS transporters. This article encompasses the important genes and their respective roles of both the classes of the transporters in different species of fungi.

Background: Klebsiella pneumoniae is a bacterial species that often causes infections in humans. Infections occur most frequently in hospitalised or immunocompromised patients and are treated with antimicrobials. In recent decades, K. pneumoniae has developed significant resistance to many antimicrobials. Objective: The main goal of this study was to determine the frequency of resistance of isolated K. pneumoniae strains from urine samples of hospital patients and outpatients, and to find evidence of ESBL strains and their resistance to certain antibiotics. Methods: During the study period, Klebsiella pneumonia was isolated from the urine samples of 430 patients. The procedure for processing of urine samples, identification, susceptibility toward antimicrobials and evidence of ESBL strains were carried out according to the recommended standards. Results: Of the total K. pneumoniae isolates, 153 (35.6%) were isolated from hospital patients and 277 (64.4%) from outpatients. Strains isolated from hospital patients were resistant to each tested antibiotic. ESBL strains were detected in 169 (39.30%) samples, 92 (60.13%) from hospital patients and 77 (27.8%) from outpatients. Conclusion: Strains of K. pneumoniae isolated from the urine of hospital patients and outpatients have developed significant resistance against all tested antibiotic substances. A higher occurrence of ESBL strains was observed in hospital patients than in outpatients. ESBL strains were resistant to all penicillins and almost all cephalosporins. Highly effective antimicrobials were amikacin, colistine, carbapenem and fosfomycin. The best therapeutic results were achieved when patients were treated with fosfomycin and imipenem.

Background and Purpose: Transverse myelitis (TM) is a rare neurological diagnosis found in 1-4 per million people. Rehabilitation is recommended secondary to steroid treatment. There is limited clinical research on physical therapy (PT) for TM. The purpose of this case report is to present PT examination and management strategies for a patient with TM. Case Description: A 25-year-old female patient diagnosed with TM was referred to PT. She presented foot drop causing ataxic gait, decreased sensation in bilateral lower extremities, significant fatigue, and low back pain. The patient required significant rest time between all tests and measures due to severely increased fatigue. PT plan of care was focused on therapeutic exercises per patient tolerance, passive range of motion (ROM) administered by the therapist, and gait training when activity tolerance was increased. Outcomes: The patient was able to tolerate bouts of exercise as prescribed through home exercise program. She responded very well to passive ROM treatment during breaks between exercises to maintain ROM and decrease rigidity. Active ROM exercise was used to build activity tolerance while being mindful of limited ability due to fatigue. Upon increased activity tolerance, the patient was able to tolerate gait training with multiple breaks and maintain corrected gait when addressed during treatment. Discussion: PT intervention was helpful for this patient with TM. Breaking down functional activities based on patient tolerance is important when treating people with TM. More experimental research is needed to support the benefits of PT for TM.

Radiation of different wavelengths can kill living organisms, although, the mechanism of interactions differs depending on their energies. Understanding the interaction of radiation with living cells is important to assess their harmful effects and also to identify their therapeutic potential. Temporally, this interaction can be broadly divided in three stages – physical, chemical and biological. While radiation can affect all the important macromolecules of the cells, particularly important is the damage to its genetic material, the DNA. The consequences of irradiation include- DNA damage, mutation, cross-linkages with other molecules, chromosomal aberrations and DNA repair leading to altered gene expression and/or cell death. Mutations in DNA can lead to heritable changes and is important for the induction of cancer. While some of these effects are through direct interaction of radiation with the target, radiation can interact with the surrounding environment to result in its indirect actions. The effects of radiation depend not only on the total dose but also on the dose rate, LET etc. and also on the cell types. However, action of radiation on organisms is not restricted to interactions with irradiated cells, i.e. target cells alone; it also exerts non-targeted effects on neighboring unexposed cells to produce productive responses; this is known as bystander effect. The bystander effects of ionizing radiations are well documented and contribute largely to the relapse of cancer and secondary tumors after radiotherapy. Irradiation of cells with non-ionizing Ultra-Violet light also exhibits bystander responses, but such responses are very distinct from that produced by ionizing radiations.

The isolation of phytase using Pichia Pastoris under methanol/sorbitol co-feeding induction technique was investigated. The biological activity of extracellular phytase after optimization with co-substrates induction in 4 liters fermentor (NBS) increased to 13250 U/ml. This led to a 509 fold increases in comparison to the other type of phytase. This effect was studied via induction with sorbitol/methanol in fermentation by Pichia Pastoris GS115 (Mut+) at 20 °C. The interference of by products; methylal, hexamine and (S)-(+)-1,2-propanediol with release of phytase in Pichia Pastoris under methanol induction were detected and cannot be repressed by methanol induction alone. The TLC was used for glycerin analysis under methanol/sorbitol induction and the results were lesser compare to that obtained during phytase production under methanol induction alone. This work showed the higher expression of heterologous proteins and by fed batch fermentation; the expression identified an advantage of producing a significant activity of phytase. Practical applications Plant derived products including sorbitol have been used as alternative medicines for the therapeutic treatment of various diseases, food supplements and could be used in many manufacturing processes. It serves as a culture media for bacteria, and helps to distinguish the pathogenic E. coli O157:H7 from its most other strains. Cells growing on methanol require high oxygen consumption. Sorbitol was used as an alternative cheap co-feeding for the production of proteins and is a non-repressing carbon source for AOX1 promoter with no effect on the level of r-protein at its induction phase. This report describes the isolation of phytase using Pichia Pastoris under methanol/sorbitol co-feeding induction techniques, and sorbitol showed to be a promising co-substrate, as it could enhance both cell growth and targeted protein productivity. This co-feeding and fed-batch induction technique was used for recombinant phytase production in a small and large scale production and the metabolites were analyzed.

It is known today that psycho-trauma and PTSD cause different levels of mental and social dysfunction. Human spirituality and capacity to meet further life difficulties become severely damaged. There is wide accepted attitude today that in holistic approach in process of healing PTSD and psycho-trauma is necessary to include other professionals from community resource regarding needs of trauma victims. In Bosnia and Herzegovina after very severe war (1992-1995) as mental health professionals, we are faced with increasing number of different mental health disorders as result of severe trauma experiences. Regarding community based care orientation it is necessary to include and religion professionals. According national and religious background of majority of our population in Tuzla Canton that is Muslim, we meet spiritual needs of our clients as needs for Islamic explanation of life and death meaning. Our clients need to talk about spiritual issues in daily therapy and to practice daily religious rituals. Regarding that in this paper we tried to interface Islamic principles and it’s beneficial toward psycho-trauma and PTSD, as well as Muslim perspectives in attempt to apply spiritual practice in therapeutic tools for better efficacy in spiritual healing of mental dysfunction’s of believers who survived severe trauma, especially war trauma.

Objective: To investigate the effect of kinesio tape and therapeutic ultrasound on pain and hand grip strength associated with tennis elbow. Material and Methods: Twenty male and female patients with age from 20-50 years suffering from lateral epicondylitis were participated in this study. All patients were randomly selected from orthopaedic surgeon. They were dividing into two groups. Group (A) (ultrasound and exercises group). Group (B) (kinesio tape and exercises group). The hand-held dynamometer was used to provide a detailed and objective measurement of wrist joint strength throughout its range of motion, the pressure being registered in kilogram (Kg) and Visual Analogue Scale (VAS) was used to record the degree of pain intensity. Result: The result shows no significant difference between group A and B in their ages, weights, heights, and BMI where their t and P-values were (0.8, 0.43), (0.03, 0.97), (0.98, 0.33), and (0.9, 0.37) respectively. In Group A the significant differences in hand grip strength between pre and post-test which shows 31.59), compared to the pre-test (27.35), while in group B (33.17) compared to the pre-test (23.88). According the pain scale for group A and group B there are significant differences where the results were (2.50), compared to the pre-test (5.90) and (2.00), compared to the pre-test (7.30), retrospectively. Conclusions: The treatment was improvement between both groups. However, the kinesio tape is better than therapeutic ultrasound.

The patient with an oncological disease presents a series of discomforts related to the psychological sphere such as depression, pain, sense of usefulness, anger, but also inconveniences related to food sphere. Neoplastic disease interferes with eating behaviour for several reasons. The communication of the diagnosis can create a state of anorexia as a result of the shock; certain tumours of the gastrointestinal tract-gold (mouth, esophagus, stomach, colon and rectum, but also pancreas and liver) are directly responsible for the possible alteration of food intake; alteration in eating behaviour may be secondary to the main therapeutic treatments. The link between food and cancer is not only evident in case of disease, but also in case of prevention, in fact a growing number of studies indicates more an more clearly the close correlation between a healthy diet and prevention of oncological diseases although at present time it is not still possible to give definitive results. The diagnosis of a person is like a melody in which some notes are repeated but their combination is almost infinite, because each person has different eating needs, as well as different psychological needs, and the starting point for a good professional must necessarily be a ‘customized’ diagnosis. This ‘diagnosis of well-being’, tailor-made for each person, involves professionals in both the food and psychological and behavioural sectors, since the individual needs have to be evaluated globally. Finally, the professionals of human behaviour in food consumption, and the chemical and science processing experts, have the duty not to limit themselves to a single refusal against the use of certain foods, but framing the phenomenon in a wider perspective and, as experts of human health, to propose alternatives.

Ra-223 dichloride is a first-in-class alpha-emitting radiopharmaceutical recently introduced into clinical practice for treatment of men with Castration-Resistant Prostate Cancer (CRPC) and symptomatic bone metastases. Due to the proven benefit on Overall Survival and the favorable toxicity profile, Ra-223 therapy is gaining widespread use in both US and Europe. In this article, we describe the routinary management of patients undergoing Ra-223 treatment in our Institution. Currently, Ra-223 therapy is indicated for 6 intravenous injections (55 kBq per kg of body weight) administered every 28 days. In comparison to other radiopharmaceuticals, Ra-223 handling and administration do not need any additional training for authorized users. Due to the minimal external dose rate emission, Ra-223 dichloride can be delivered in an outpatient setting. Moreover, no particular precautions other than standard hygiene measures must be taken by patients’ family members or caregivers. Ra-223 therapy is associated to a favorable hematologic toxicity profile, while non-hematologic adverse events are generally mild and easy to manage. Given the favorable toxicity profile of this treatment, clinical trials are currently ongoing to evaluate efficacy and safety of Ra-223 treatment in combination or sequence with recently approved drugs such as abiraterone acetate, enzalutamide and sipuleucel-T. In addition, the recent interest in Ra-223 bone lesion dosimetry could open the way to a dosimetric-based therapeutic approach with Ra-223. In this new scenario, results of these promising clinical trials may help clarifying the optimal sequencing of new therapeutic possibilities for metastatic CRPC and the appropriate eligibility criteria for Ra-223 treatment in oncologic patients.

The well recognized white adipose tissue is an endocrinal organ secreting various hormones and this article simply indicates to the physiologic concepts brown fat tissues (BAT) which are extremely active endocrine organs and play various metabolic active roles in intermediate metabolism. The physiologic function of Brown adipose tissues contributes to energy-producing parts of the cell. Its amount is rare up to approximately one hundred and thirty gram and implies important characteristics for mammals. An increase in energy expenditure could be an aim by activation of BAT, seems futurity to reduce body weight that needs a vast majority of fundamental research to facilitate its occurrence [1]. Brown fat tissue generates heat and has valuable importance for human metabolism [2,3]. Brown fat tissue is decreased in overweight and obese people and possibly activating brown fat tissue might help for reducing weight and weight-related metabolic disorders like insulin resistance.

Understanding the obesity-related genes may provide future therapeutic strategies to modulate disease progression. UCP2 separates oxidative phosphorylation (OXPHOS) from ATP production in the inner mitochondria. Figure 1 shows the differences among UCP1, 2, 3. The main role of UCP2 is controlling the metabolism of energy in the cells [1-3]. Besides that, the expression of UCP2 is associated with chronic inflammation due to reactive oxygen species (ROS). In this regard, in injured cells and tissues, ROS could be decreased by reducing the proton motor force by the anti-inflammatory effect of UCP2 [4].

Chemotherapy is one of the main treatment options for cancer. However, chemotherapeutic agents usually suffer from poor pharmaceutical properties that restrict their use. Targeted therapy drugs have been developed to specifically target changes in cancer cells that help these cells to grow. Such drugs often work when standard chemotherapeutic drugs do not, they often have less severe side effects and they are most often used for advanced cancers. The objective of this article is to give an overview about the 16 FDA-approved targeted therapy drugs to treat non-small cell lung cancer.

Introduction: the perennial pandemic: There are serious challenges posed by the SARS-CoV-2 virus and COVID-19 as the disease. With the persistence of the pandemic over one and half year, it is being feared that the COVID-19 may have become the new reality associated with human existence world over and the mankind may have to live with it for years or even decades. Further, the grievous nature of the disease is evolving further with genomic changes in the virus in form of mutations and evolution of variants, with enhanced infectivity and probably virulence. Acute and chronic phases of COVID-19: Epidemiologically, it is becoming clear that apart from the advanced age and pre-existing conditions, such as diabetes, cardiovascular, pulmonary, and renal diseases, certain constituent factors render some patients more vulnerable to more severe forms of the disease. These factors influence the COVID-19 manifestations, its course, and later the convalescence period as well as the newly defined ‘Long COVID phase. The substantial continuing morbidity after resolution of the infection indicates persisting multisystem effects of ‘Long Covid’. Lung damage associated with COVID-19: COVID-19 is primarily a respiratory disease presenting with a broad spectrum of respiratory tract involvement ranging from mild upper airway affliction to progressive life-threatening viral pneumonia and respiratory failure. It affects the respiratory system in various ways across the spectrum of disease severity, depending on age, immune status, and comorbidities. The symptoms may be mild, such as cough, shortness of breath and fevers, to severe and critical disease, including respiratory failure, shock, cytokine crisis, and multi-organ failure. Implications for the post-COVID care: Depending on the severity of respiratory inflammation and damage, as well as associated comorbidities, duration of injury and genetics, the progressive fibrosis leads to constriction and compression of lung tissues and damage to pulmonary microvasculature. Consequently, the COVID-19 patients with moderate/severe symptoms are likely to have a significant degree of long-term reduction in lung function. Depending on the severity of the disease, extensive and long-lasting damage to the lungs can occur, which may persist after resolution of the infection. Managing the long COVID’s challenges: Given global scale of the pandemic, the healthcare needs for patients with sequelae of COVID-19, especially in those with lung affliction are bound to increase in the near future. The challenge can be tackled by harnessing the existing healthcare infrastructure, development of scalable healthcare models and integration across various disciplines with a combination of pharmacological and non-pharmacological modalities. Following clinical and investigational assessment, the therapeutic strategy should depend on the disease manifestations, extent of damage in lungs and other organs, and associated complications.

From the first case of primitive cardiac surgery (CS), treatment of stab wound of the heart (Dr. Daniel Hale Williams, 1893), to recent surgical procedures and device implantations for end-stage heart failure (HF), the CS has grown and emerged in the public health more and more [1]. The heart valve disease had interested immediately since the non-cardiopulmonary era because of the multitude of rheumatic patients and congenital valve disease. In the 1952, Hufnagel implanted the first valve in descending aorta and it was the sign of the first step of the CS evolution. New prosthesis and heart valve techniques were tested between 1970 and 2000 with optimal results in patients’ quality of life and survival, at the same time of CPB evolution. Whilst, the evolution of heart valve surgery had stimulated new devices, prosthesis and the development of minimally invasive surgery, this was partially diminished by the spreading of trans catheter valve implantation. In the 2002, Dr. Alain Crabbier described a non-surgical prosthetic valve implantation firstly: it was the revolution of CS evolution [2]. The transcatheter valve implantation has evolved and spread rapidly with multiple approaches femoral to apical, aortic, axillary and carotid, and many suitable and technological devices. The higher and higher risk patients, the needs to avoid surgical complications, the evolution of available devices and the fabrication of new technologies have increased the efforts to improve trans catheter valve implantation [3]. The recent article of Loyalka et al, described a special case of tricuspid valve in valve replacement with Sapien 3, an innovative and alternative therapeutic choice to a tricuspid valve degeneration [4]. Instead, Sawara et al [5], documented as trans catheter aortic valve implantation for a failing surgical bio prosthesis or native aortic valve regurgitation has become an alternative for patients at high risk for redo surgical aortic valve replacement or aortic regurgitation since now off-label: that was a reliable and significant results in the era of trans catheter valve implantations. What would we attend from the future? In the most surgical centres, the trend were a significant decrease in patients undergoing to open-heart valve surgery compared to trans catheter valve implantation. Maybe the new ongoing studies of lower and mild-risk patients undergone to transcatheter procedure would open either a deeper collaboration of the heart team and a new therapeutic perspectives in the public health with a shift to more minimally invasive procedures, less day of hospitalization and I don’t see why not less costs for public health.

Background: Herbal essential oil contains pharmacological benefits for intervention treatment of various diseases. Studies have demonstrated its antimicrobial, antioxidant, and anti-inflammatory effect involving in vitro cell culture and preclinical animal models. It has been also traditionally used to reduce anxiety and hypertension in human. However, scientific studies elucidating its mechanism of action and pharmacological targets, as well as its effectiveness and safety as phytotherapeutic compounds are still progressing. Recent studies showed its promising effect in depression-cardiovascular disease intervention. However, comprehensive evaluations to enlighten latest advancement and potential of herbal essential oil are still lacking. Objective: In this systematic review, the depression-cardiovascular effects of herbal essential oil on lipid profile, biochemical and physiological parameters (e.g haemodynamic) are presented. The route of delivery and mechanism of action as well as main bioactive compounds present in respective essential oil are discussed. Methods: Article searches are made using NCBI PubMed, PubMed Health, SCOPUS, Wiley Online, tandfonline, ScienceDirect and Espacenet for relevant studies and intellectual properties related to essential oil, depression and cardiovascular disease. Results: In experimentation involving in vitro, in vivo and clinical trials, herbal essential oil showed its effectiveness in reducing coronary artery disease (narrowing of the arteries), heart attack, abnormal heart rhythms, or arrhythmias, heart failure, heart valve disease, congenital heart disease, heart muscle disease (cardiomyopathy), pericardial disease, aorta disease, Marfan syndrome and vascular (blood vessel) disease. Conclusion: This review gives a valuable insight on the potential of essential oil in the intervention of depression associated with cardiovascular diseases. Studies showed that herbal essential oil could act as vasodepressor, calcium channel blocker, antihyperlipidemia, anticoagulant, antiatherogenesis and antithrombotic. It can be proposed as an interventional therapy for depression-cardiovascular disease to reduce doses and long-term side-effect of current pharmacological approach.

In the actual medical therapy of BPH, we can see: antibiotics, alpha blockers, 5-ARI, fitotherapeutics/natural products (Serenoa repens) with different which display clinical activities and other molecules such as FANS (local or systemic dosage forms) cortisones and others. Relationship between immune systems and chronic prostatitis are strictly involved in BPH progression. A vicious cycle that involve chronic flogosis, tissue remodeling, grow factors, inhibition of apoptosis, and other phenomena. Observing BPH pathogenesis under an immunologic point of view make possible to search new pharmacological strategies, to improve actual therapy. The aim of this work is to observe some relevant literature in our opinion related the management of BHP and its progression under a pharmaceutical and immunological point of view. A deep knowledge in the pharmaceutical properties of some molecules (antimicrobials, anti-phlogosis agents, Anti-androgenic agents, alpha blockers, 5-ARI and other treatments, techniques, interventions or instruments) can help the physicians to pick the right choice.

There is evidence that complement components induce cell migration in mesenchymal stem cells and regulate cytokine production in osteoblastic cells thus playing a regulatory role in normal bone formation. The aim of the present study was to investigate the involvement of complement system in the differentiation of bone marrow cells in complement-depleted model of rheumatoid arthritis (RA). Arthritis was induced by intraarticular injection of zymosan in cobra venom factor (CVF)-treated mice depleted of functional complement. The expression of different markers by bone marrow [1], on fibroblasts (CD29), mesenchymal cells (CD105), dendritic cells (CD14, CD86), osteoclasts (CD265), cells expressing Dectin1 (CD369) and megakaryocytes (CD62P) was determined by flowcytometry. The lack of functional complement activity at the point of arthritis initiation (day 3) lead to an increase of fibroblast and megakaryocyte populations, to a decrease of mature and dectin1 positive populations, while the number of mesenchymal cells was not changed, all compared to arthritic mice. Immunohistochemical staining showed that low complement activity diminished arthritis-induced generation of megakaryocytes and platelets in BM. Chronic inflammation during erosive conditions such as rheumatoid arthritis, leads to dysregulated differentiation and prolifеration of bone cells, inflammation of synovial membrane and bone marrow, and degradation of cartilage and bone. Present results point that the lack of functional complement changed the ratio between different cell populations that can be used for determining the development and stage of rheumatoid arthritis and can help finding of new therapeutic approaches.

Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono-or bi-substituted/crosslinked adducts) or -OH groups (to form ester linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological and pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, and Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, supranuclear palsy, Huntington’s disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. Here we describe the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.