therapeutic

Introduction: Radioiodine therapy is a standard procedure in thyroid autonomy treatment. Discrepancies in the visual comparisons of the scintigraphies prepared for this purpose using Tc-99m-O4- and I-131 have been known for years. In this study a new method is used to calculate and perform a quantitative comparison of both uptakes using subtraction analysis and 3D imaging. The results and their causes are discussed together with practice-relevant conclusions for better clinical results. Material and Methods: The new method was used in 38 patients with thyroid autonomies for the subtraction analysis of standardized pretherapeutic and intratherapeutic scintigraphies. The parametric distribution of activity was calculated absolutely and as a percentage and displayed three-dimensionally. These results were compared with the visual assessment of the different scintigraphies by the experts. Inclusion criteria were pretherapeutic and intratherapeutic hyperthyroidism without medication affecting the thyroid. The time difference between acquiring the scintigraphies was 28 days maximum. Results: Activity distribution was visually discrepant in 39.5% of cases. 60.5% displayed comparable uptake. The calculated values showed reversed results after applying the new method. The results using our method show a higher rate of calculated discrepancies compared with visual analysis. Conclusion: Accurate functional imaging of the thyroid is next to further aspects very important in establishing the diagnosis and deciding about the therapy activity for thyroid treatment. In combination with clinical symptoms and laboratory values, Tc-99m-O4 - scintigram can be used for an orientated, preliminary assessment of functional disorders of the thyroid. But because of the higher rate of found discrepancies, the solely use of Tc-99m-O4 - scintigram is not always capable for exact and reliable diagnosis. The known reason for this is most probably due to the different biokinetics of both radiopharmaceuticals, which can be imaged more sensitively with this method. Consequently, a scintigram should be performed in the pretherapeutic radioiodine uptake test. Despite higher costs and radiation exposure, alternatively, pretherapeutic use of other diagnostic iodine isotopes like I-123 or -124 should be discussed, because they could overcome the limitation of the different biokinetics. Following this approach the preliminary assessment using Tc-99m-O4 - scintigraphy can be precised and double checked to improve diagnostic confi dence and treatment results for a better outcome of the patients.  

Prostate specific membrane antigen, a type II transmembrane protein is an excellent target for the radionuclide therapy in advanced prostate cancer patients due to its high expression in the prostate cancer cells. We present the case of a 69-year old man with advanced metastatic castration resistant prostate cancer. In view of rising serum PSA levels despite hormonal and chemotherapy, we decided to perform a 68Ga-PSMA-HBED-CC PET/CT scan (prostate specific membrane antigen). It revealed intense radiotracer uptake in the prostate, lymph nodes and multiple skeletal sites. Five cycles of 177Lu-PSMA-DKFZ-617 radioligand therapy were administered in the patient followed by an intrim 68Ga-PSMA-HBED-CC PET/CT. Intrim 68Ga-PSMA-HBED-CC PET/CT scan demonstrated a near complete remission of disease with a corresponding decrease in the sPSA levels. During the follow-up duration of 12 months, the patient did not develop haematological, kidney and liver toxicity during the course of treatment and follow-up. 177Lu-PSMA-DKFZ-617 is a promising therapeutic option in metastatic castration resistant prostate cancer (mCRPC) patients.

Breast cancer is a complex disease and one of the main causes of cancer-related mortality in women worldwide. In case of approximately 15% of all breast cancers, three markers i.e. estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptors-2 (HER2) are not expressed, and is commonly termed as triple-negative breast cancer (TNBC). Particularly, TNBC is associated with a higher percentage of breast cancer related mortality, which is often aggressive and most frequently found with a BRCA1 mutation or increased basal marker expression. However, due to the limitations of chemotherapy and radiation based treatment; the current challenge is to establish a new strategy of diagnosis and treatment of TNBC. The deregulation of a number of microRNAs (miRNAs) in breast cancer has been widely reported. Therefore, this review is directed towards enhancing our understanding of the involvement of various miRNAs in the pathology of TNBC, their upregulations and downregulations and the effects on various factors. From recent studies a number of miRNAs are found to be related with TNBC, which have great potential to be used as a biomarker to determine the disease prognosis and predict the fate of disease. Again miRNA can be targeted to be applied as a therapeutic to provide a great benefit to the patients of TNBC by finding a new, safe, and effective treatment strategy.

The Transcatheter Aortic Valve Implantation (TAVI) had emerged more and more in the last twenty years. According to the scientific literature, this is an approved, suitable and alternative therapeutic choice to conventional surgery for aortic valve disease in high risk patients. The most of patients are octogenarians or nonagenarians, with multiple comorbidities (neurological,vascular,oncologic, haematological, etc). The evolution of TAVI techniques and its devices have improved the quality of results and reduced the peri- and post-procedural complications. Cardiac anaesthesia and analgesia in TAVI patients is very important and fundamental to a quickly and complete clinical restoring after the procedure. An optimal balance of drugs and peri-procedural management could reduce the neurological events (such as delirium), the days of hospitalization and the admission of intensive care unit. According to our experience in transapical approach, the low dose of propofol and desflurane allowed to optimal cardiac anaesthesia and rapid mechanical ventilation weaning in complex patient undergone to transcatheter valve implantation with transapical approach. Moreover, our protocol reduced considerably the incidence of perioperative delirium.

The RNA interference (RNAi) technique is a new modality for cancer therapy, and several candidates are being tested clinically. Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of ‘personalized medicine’. Technologies on theranostic nanomedicines has been discussed. We designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90 nm, bright green fluorescence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. This chapter presents an over view of the current status of translating the RNAi cancer therapeutics in the clinic, a brief description of the biological barriers in drug delivery, and the roles of imaging in aspects of administration route, systemic circulation, and cellular barriers for the clinical translation of RNAi cancer therapeutics, and with partial content for discussing the safety concerns. Finally, we focus on imaging-guided delivery of RNAi therapeutics in preclinical development, including the basic principles of different imaging modalities, and their advantages and limitations for biological imaging. With growing number of RNAi therapeutics entering the clinic, various imaging methods will play an important role in facilitating the translation of RNAi cancer therapeutics from bench to bedside.

We evaluated a total of 115 patients diagnosed with anal cancer, who were treated at our clinic from 1995 to 2012. Their average age was 61 years, most often were diagnosed in stages II and III, in most cases it was a squamous cell carcinoma located in the anal canal. The mean follow-up was 83 months (minimum 1 month and maximum 240 months). We combined external radiotherapy with boost of brachytherapy or boost of external radiotherapy and possibly a combination of both boosts. Half of the patients received concomitant chemotherapy. We specifically evaluated local tumor regression, overall survival and the impact to therapeutic effect of the chosen irradiation technique. Complete regression was achieved in 92 patients, partial regression in 21 patients. Overall survival, regardless of stage, was 80% 3-year, 74% 5-year and 67% 10-year. The age of patients, the size of their own primary tumor and the therapeutic method used had a statistically significant effect on survival - especially the importance of brachytherapy was irreplaceable.

In 1874 J.M. Charcot was the first to describe ALS amyotrophic lateral sclerosis, a disease with an high non response therapy rate also to the actual therapy. ALS is not clearly associate to only single etio-patogenetic movens but many process seem involved. Also the strange geographic diffusion of different forms contribute to a complex syndromic pathology. The introducing of new theories and approach can help to find more efficacy therapeutic strategies. In this work the different neuronal damage movens and new therapeutic strategies are analyzed to produce a Unic global response to the pathologic process useful in next clinical application. Genetic factors must be considered also added to environmental movens but also to the endogenous microenvironment of motoneuron involved. A toxicological-biochemical-imunological approach can be useful tool to find new therapeutic strategies. Or to improve local availability of pharmacological molecules.

In various patients conditions involved in lower urinary tract disease LUT (like overactive bladder, bladder neck sclerosis, dis –synergy (with our synenrgic contraction between bladder detrusor and bladder neck, BPH, recurrent cysytitis, interstitial cystitis, chronic prostatitis, uretral stenosys, loss of sfinteric coordination. Prostatic cancer, anatomic abnormalities and other the receptor status play relevant role to reduce effect of vicious clycle that can be responsible in progression of the pathologic process. In this work the complex receptorial status is analyzed to verify new therapeutic strategies. Starting from the observation that various irritant substanties produce irritant stimulus in Prostatic Patients or in bladder neck condition is interesting to deep understand the etio-patogenesys and Functional results. In Various prostatic, bladder neck or ureteral condition a reduced urinary fluss can produce infectious. Conditions like acute or chronic prostatitis. Irritants sustanties in diet (in example etilic alcohol drink, hot spices, crud meats, carbonate drinks, caffeine and other) can produce Painful stimulus in innervations of vecical trigonous, bladder neck and prostatic urethra. The same recurrent cystitis and Bph contribute in a complex situation. This stimulus produce ipertonus of bladder muscle involved in the expulsion of urine. The event related inflamation and edema (bladder, prostatic uretra, trigonus) contribute to the global effect. So conditions like bladder neck sclerosys IPB, recurrent prostatitis and cistitys in acts in a vicious circle. (Also immunomediated: Bph and cronic prostatitis with linfocite infiltration and tissue remodeling). The ormonal status check the systems (see 5-ARI efficacy in Bph). Simpatic, parasimpatic and other system are deeply involved. Also behavioral habits or diet can influence in example urinary flux in a complex system like LUT. (Bladder and prostatic irritants that can produce edema and acute inflamation). Other behavior habits are deeply involved as too much sedentary, water intake, coffee, pee modality and also psychological profile and stressing conditions. Some disease like diabetes produce high consequences in all this systems due to Bladder modification, oxidative stress, osmotic movens, and increase susceptibility of urinary infections. This article are verified this kind of movens that contribute in physio -pathology of some low urinary tract conditions. The anatomic abnormalities produces, obviously, physiological disfuntions. Recurrent urinary tract infections, inadequate antimicrobial therapy: Profile of resistance, duration of therapy, kind of antimicrobials, posology, Pk. Kinetics, associations, compliance, biofilms, micro calcifications (recurrent chronic prostatitis) contribute to a progression of the condition.

Introduction: Candidiasis is more frequent in human immunodeficiency virus (HIV)-infected patients and knowledge about the distribution and antifungal susceptibility of oral Candida species is important for effective management of candidiasis. Material and Methods: An oral rinses sample collected from hundred HIV-infected patients with and without clinical evidence of oral candidiasis in this study at the Infectious Department/Tripoli Medical Center, Libya. Species identified by standard phenotypic and conventional methods and in vitro susceptibility testing of the yeast isolates to antifungals were performed using the Disc diffusion method protocol as recommended by the Clinical Laboratory Scientific Institute. Results: Oral Candida colonization is detected in all patients with and without clinical syndromes, and Candida albicans were accounted for (74%), C. dubliniensis (11%) and C. glabrata (6%). A high proportion of Candida species (42%) showed decreased susceptibility to fluconazole. Among C., albicans more than 30% of isolate were resistant to most new azole antifungal including fluconazole, itraconazole, posoconazole and voriconazole. Conclusions: A significant number of oral Candida species particular Candida albicans exhibiting decreased susceptibility to fluconazole were isolated from colonized HIV-infected individual, given the high incidence and severity of fungal infections in HIV-infected individuals. The results of this study reinforce the importance of antifungal susceptibility testing, which contributes to the therapeutic strategies and highlights the need for continuous surveillance of Candida colonization in this population.

Breast cancer is the most common cancer in women and is a major public health problem. It is divided into several subtypes, including triple negatives. The general objective of our study is to establish the profile and the management of patients with triple negative breast cancer over a period of 2 years, operated in our department. During our study period, triple-negative breast cancers accounted for 10% of our population. The most affected age group ranges from 50 to 60. The majority of patients in our sample are pauciparous. In the group of patients who received hormone therapy, it was mainly HRT for 4 to 6 years. 96.77% of patients consulted a health worker within 3 months of the discovery of the signs. Adenopathies are frequently present at the time of diagnosis. 93.54% of the cases have an invasive ductal carcinoma. Triple negative cancers are essentially poorly differentiated. Triple-negative cancer has a high rate of cell renewal. In our study, neoadjuvant chemotherapy is mostly indicated for triple-negative breast cancers ≥ 30 mm at diagnosis and a delayed lumpectomy is then performed in 23.52% of the patients. For tumors of < 30 mm size, a lumpectomy is performed immediately in 76.47% of the patients, followed by adjuvant chemotherapy. Mastectomy was performed in 45.16% of patients; it was mainly indicated in front of a large tumor size associated with a small breast volume, then multifocal breast tumors. Breast reconstruction was performed in 21.42%. Radiation therapy is indicated in the majority of patients, postoperatively. In our population, 11 patients were proposed to have an oncogenetic survey; it was mainly indicated based on the Manchester criteria in front of a young age and a family history of cancer. There are two BRCA 1 mutations, one BRCA 2 mutation, and one case of absence of mutation. The therapeutic intake in case of a mutation is directed towards a prophylactic bilateral mastectomy and adnexectomy, proposed at the age of 40. Two patients had presented triple negative recurrences of their already treated breast cancer; first case PDL1 positive PD-L1 ≥ 1% treated with immunotherapy combined with chemotherapy (atezolizumab/abraxane) while the second and second PDL1 negative treated with chemotherapy alone. Despite their low frequency, triple negative breast cancers represent a subgroup marked by pejorative characteristics, a reserved prognosis, with limited treatment options.

Filariasis is one of the Neglected Tropical Diseases (NTDs) known to be of serious public health importance and pose devastating socio-economic burden especially among the poor people in tropical and subtropical countries of the world. The parasite is responsible for lymphatic filariasis affecting about 1.3 billion people in 72 countries worldwide. The major parasitic agents of the infection are three closely related nematodes of clade Onchocercidaei namely Wuchereria bancrofti, Brugia malayi and B. timori that are transmitted to human through bites by mosquitoes of genera: Aedes, Anopheles, Culex and Mansonia. The disease is targeted by the World Health Organization (WHO) for elimination by 2020 through the use of chemically synthesized drugs used as therapeutic agents to cure the disease but there are some setbacks. Phytochemical extracts are viewed as alternative therapy in the management of the disease. Additionally, the species have many ecological variants and are diversified in terms of their genetic fingerprint. This diversification in terms of genomic sequences as well as rapid infection rate warrant the lymphatic filarial parasites to respond differently to diagnostic and therapeutic interventions. Thus understanding the genomic diversity of the parasite will help in efficient therapeutic management of the disease, thereby eliminating it to prevent unnecessary suffering and contribute to the reduction of poverty. In this review, we have highlighted on the used for phytochemical extracts in the therapeutic management of the lymphatic and the molecular genetic diversity of the parasite was delineated.

Artocarpus (Moraceae) is a deciduous tree with appreciable importance as a source of edible fruit and is widely used in folk medicines. The extracts and metabolites of Artocarpus heterophyllus particularly those from leaves, bark, stem and fruit possess several useful bioactive compounds. This review indents to compile various studies on A. heterophyllus and critically evaluates its ethnomedical and ethnopharmacological properties. Several pharmacological studies from A. heterophyllus have conclusively established their mode of action in anti-inflammatory, antimicrobial, antioxidant and anticancer activities. Based on the available data, it is concluded that Artocarpus as a promising source of useful products and opens up new avenues for novel therapeutics.

Currently, the emergence of highly virulent mutants in Europe and the United States has caused refractory recurrent Clostridium difficile infection (RCDI) to be a problem in clinical practice. In 2013, the Netherland group demonstrated breakthrough therapeutic efficacy in fecal microbial transplant (FMT) treatment clinical trials for RCDI, and FMT treatment is rapidly gaining attention. In addition to RCDI, FMT treatment has been attempted in various gastrointestinal diseases such as inflammatory bowel disease, irritable bowel syndrome and chronic constipation, as well as extragastrointestinal diseases. In this review, I would like to describe the current status, complications and prospects of FMT treatment.

Aim of this work is to analyze the coronavirus viral surface properties related the pattern of electrical features. This chemical physical property is relevant and crucial to set profile of diffusion, severity of disease, efficacy of therapeutic strategy and in order to search new way to fight COVID-19 and the NEW VARIANT. The phenomena of immune evasion and the different pattern of efficacy towards variants of some vaccine or some antibodies combination produce the need to verify if considering the electrical feature of viral surface can be a right tool or not. As result of this research it is possible to submit to the scientist that the viral surface properties and electrical feature can be an element to be considered in various preventive or treatment measure. The specificity of action of some vaccine or antibodies seem to tell us that also the aspecific methods are useful. A specific chemico physical factors can influence the electrical charges viral surface behavior. Hpertonic saline solution, humidity, electrical charge barrier in mask are simply example of the effect. That can be obtained action on viral surface chemico -physical properties.

It is difficult to predict how the founder of psychoanalysis, Sigmund Freud, would react to an attempt to link his theory and the method of treating mental disorders based on it [1], with such a purely physical disease as acute pneumonia (AP). It is unlikely that such an innovation could cause full approval and support. However, in this context, we are not talking about psychoanalysis as a therapeutic method for AP. In this case, only the diagnostic features of this technique are of interest

Tea (Black tea and Green tea) are one of the most widely consumed beverages in the world. However, with the increasing interest in the health properties of tea and a significant rise in scientific investigation, this review covers some of the recent findings on the health benefits of both green and black tea. The mechanisms of action of various black and green tea components have been presented. Green tea contains a unique set of catechins that responsible for its biological activity potentially relevant to the prevention of diseases. Although there has been much focus on the biological property of the major tea catechins, black tea offers major health benefits either due to the presence of the catechins in epimerized form or some other active components of both varieties of tea. Characteristics unrelated to the antioxidant properties of green and black tea might also be responsible for their therapeutic potential in preventing diseases. Synergistic effect of the tea constituents is increasingly recognized as being potentially important to the medicinal benefits of black and green tea. The studies indicate that tea has the potential of being a part of diet for healthy living.

Infectious bursal disease (IBD) considered as one of the major viral diseases threatening the poultry industry worldwide. The causative agent of the IBD is Infectious bursal disease virus (IBDV) which replicates in developing B lymphocytes in the bursa of Fabricius leading to its destruction and bursal inflammation. In this study, we investigated a technology to produce therapeutic recombinant antibodies against IBDV in bacteria by constructing a bacterial displayed recombinant scFv library from immunized chickens, followed by screening the scFv library by fluorescence activated cell sorting (FACS) with FITC-labeled VP2. Twelve VP2-binding scFv clones with unique sequences were obtained, with overall amino acid homology of 81.53%. The complementarity determining region (CDR) 3 in the heavy chain displayed the lowest homology, while the amino acid sequences in framework regions and CDR2 of both chains and CDR1 of the heavy chain are relatively conserved. Twelve VP2-binding scFv clones were expressed in E.coli and purified through denaturation and denaturation of inclusion bodies. Our ELISA results showed that all scFvs exhibited binding ability and specificity to VP2 and various IBDV strains. In addition, two scFvs showed significant neutralizing activity to IBDV (B-87 strain) as these scFvs inhibited cytopathic effect of chicken embryo fibroblast (DF1) caused by IBDV. In conclusion, our study provides a lead candidate for further development of therapeutic antibodies for IBDV infection.

In the current study, combinatorial therapeutic approaches to DNA/RNA of human cancer cells and Benzylpenicillin (Penicillin G), Fluoxetine Hydrochloride (Prozac and Sarafem), Propofol (Diprivan), Acetylsalicylic Acid (ASA) (Aspirin), Naproxen Sodium (Aleve and Naprosyn) and Dextromethamphetamine nanocapsules with surface conjugated DNA/RNA of human cancer cells to targeted Nano drugs for enhanced anti-cancer efficacy and targeted cancer therapy using Nano drugs delivery systems were investigated.

Red blood cell (RBC) alloimmunization can be a life-threatening complication for patients with thalassemia major and sickle cell disease (SCD) who must receive chronic therapeutic transfusions. Chronic transfusions can lead to erythrocyte alloimmunization, patients continue to develop alloantibodies due to the transference of the immunogenic antigens on the donor RBCs. Many complications are possible. Difficulty in finding compatible match units for the patients can cause transfusion delays delayed, or present alternative risks to the patients from delayed hemolytic transfusion reactions. This review discusses the possible mechanisms, risk factors associated with alloimmunization formation and the hemolytic transfusion reactions and also describe the guideline for transfusion management of these patients, including opportunities and emerging approaches for minimizing this life-threatening complication.

Amyloid-β peptide (Aβ) and tau protein deposits in the human brain are the pathological hallmarks of Alzheimer’s disease (AD). Tau is a class of proteins that are abundant in nerve cells and perform the function of stabilizing microtubules. However, in certain pathological situations, Tau proteins become defective and fail to adequately stabilize microtubules, which can result in the generation of abnormal masses that are toxic to neurons. This process occurs in a number of neurological disorders collectively known as Tauopathies. Tau protein is the major factor of the intracellular filamentous deposits that relate to a number of neurodegenerative diseases which includes the progressive supranuclear palsy (PSP), Pick’s disease, and Parkinsonism. The identification of mutations in Tau established that dysfunction or misregulation of tau protein is sufficient to cause dementia and neurodegeneration. In this review article, we discussed the etiology of the tau formation and role in AD and subsequently therapeutic approach for disassembling and Tau inhibition.