Novel Challenges for the Therapeutics of Depression: Pharmacological Modulation of Interaction between the Intracellular Signaling Pathways Mediated by Ca2+ and cAMP
Published on: 30th January, 2017
OCLC Number/Unique Identifier: 7317597566
Depression is a psychiatric disease resulting mainly by dysfunction of serotoninergic and monoaminergic neurotransmission in central nervous system (CNS). Due to the multifaceted nature of depression and our limited understanding on its etiology, depression is difficult to be treated with currently available pharmaceuticals. Then, new therapeutic strategies for depression have been proposed. Since 1975, several clinical studies have reported that L-type Ca2+ channel blockers (CCBs), used in anti-hypertensive therapy, produce increase of plasma catecholamine levels and tachycardia, typical symptoms of sympathetic hyperactivity. Despite these adverse effects of CCBs have been initially attributed to adjust reflex of arterial pressure, during almost four decades these enigmatic phenomena remained unclear. In 2013, we discovered that this paradoxical sympathetic hyperactivity produced by CCBs results from the increase of catecholamines release from sympathetic nerves, and adrenal chromaffin cells, due to its modulatory action on the interaction between intracellular signaling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signalling interaction). Then, the pharmacological modulation of this interaction by combined use of L-type CCBs, and cAMP-enhancer compounds, could be a more efficient (and safer) therapeutic strategy to produce increase of serotoninergic and monoaminergic neurotransmission in the CNS due to enhance of serotonin and monoamines release, thus attenuating clinical symptoms of depression in humans.
Immunological background for treatments with biologicals in CRSwNP
Published on: 8th April, 2021
OCLC Number/Unique Identifier: 9030352571
Background: Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial inflammatory disease of the nasal and paranasal mucosa. To date, no internationally standardized uniform classification has been developed for this disease.
Usually, a phenotype classification according to CRS with (CRSwNP) and without (CRSsNP) polyposis is performed. However, through a variety of studies, it has been shown that even within these phenotypes, different endotypes of CRS exist, each with a different underlying inflammatory pathophysiology. In this mini-review, we aim to outline the essential immunological processes in CRSwNP and to highlight the modern therapeutic options with biologics derived from this disease.
Methods: Current knowledge on the immunological and molecular processes of CRS, especially CRSwNP, was compiled by means of a structured literature review. Medline, PubMed, national/international trial and guideline registries as well as the Cochrane Library were all searched.
Results: Based on the current literature, the different immunological processes involved in CRS and nasal polyps were elaborated. Current studies on the therapy of eosinophilic diseases such as asthma and polyposis are presented and their results discussed.
Conclusion: Understanding the immunological basis of CRSwNP may help to develop new personalized therapeutic approaches using biologics. Currently, 2 biologics (dupilumab, omalizumab) have been approved for the therapy of CRSwNP (polyposis nasi) in Europe.
Update on Phenobarbital for Alcohol Withdrawal Syndrome in Intensive Care
Published on: 22nd July, 2019
OCLC Number/Unique Identifier: 8206683605
Alcohol abuse is a global health problem. Alcohol withdrawal syndrome (AWS) ranges from mild to severe symptoms that can lead to fatal delirium tremens requiring ICU admission and incurring high health care cost as high as $20,000 a month. The latest published reports suggest that phenobarbital is a promising therapeutic option for management of AWS as evidenced by less ICU admissions, length of stay in hospital, use of adjunctive agents, health care costs and attention from the nursing staff than that of patients treated with commonly used benzodiazepines such as lorazepam, diazepam, and chlordiazepoxide. Phenobarbital is beneficial for the treatment of AWS, both in the emergency and inpatient settings and both as monotherapy or in conjunction with benzodiazepines. It is safe for patients without severe hepatic impairment, has a better mechanism of action and longer half-life than benzodiazepines, and leads to less delirium and agitation. Powered randomized controlled trials with large populations are required, yet phenobarbital can be used to safely to treat AWS.
Endogenus toxicology: Modern physio-pathological aspects and relationship with new therapeutic strategies. An integrative discipline incorporating concepts from different research discipline like Biochemistry, Pharmacology and Toxicology
Published on: 14th January, 2019
OCLC Number/Unique Identifier: 7986003175
Many pathologic disease can be considered as related to an Endogenous toxicological moves and in time dependent way (kinetics and dynamic of the process). In this work starting from the analysis of relevant literature involved with different disease and related to the endogenous local micro- environment some global conclusion useful as new tools for innovative pharmacological strategies will be submitted to the researcher. Physiology, pathology concept linked to the endogenous toxicological local micro-environment status as new research instruments. The same carcinogenesis process can be related also to endogenous agents that may have a major contribution in spontaneously process. (Reactive oxygen species (ROS), which are involved in multiple cellular processes by physiologically transporting signal as a second messenger or pathologically oxidizing DNA, lipids, and proteins).
Embolic Septic Emboli with MRSA: A different source
Published on: 12th December, 2019
OCLC Number/Unique Identifier: 9272395614
Septic Iliac vein thrombophlebitis with associated psoas abscess is a rare and severe entity, which diagnosis is challenging when no risk factor is clearly present. We are presenting a case of severe septic cavitary pulmonary emboli complicated with Acute Respiratory Distress Syndrome (ARDS) that evolved rapidly to respiratory distress and multi organ failure.
A 61-year-old Hispanic male, had multiple emergency department visits due to back pain, being most of them intramuscular pain medications and steroids. In the history, he had back pain that worsened accompanied by poor mobility, generalized malaise, fever and chills. Computed tomography (CT) scan showed a paravertebral psoas abscess with L5 - S1 diskitis/spondylitis inflammatory changes, which was then later evidenced by a gallium study. Further imaging studies were done, showed bilateral cavitary lung lesions, consistent with septic emboli. Subsequent blood cultures were positive for Methicillin Resistant Staphylococcus Aureus (MRSA), for which a successful combined therapeutic regimen was used. Transthoracic and transesophageal echocardiogram were not suggestive of endocarditis. Staphylococcus aureus (SA) bacteremia is one of the most common serious bacterial infections with a high risk of metastatic complications, which makes this pathogen a unique one. The combination of factors iliac vein thrombophlebitis, psoas muscle abscess, diskitis/spondylitis with ARDS makes cavitary pulmonary disease a challenging perspective. After a 6-week antimicrobial treatment, full anticoagulation, his clinical condition and image findings improved, and he was recently admitted for physical rehabilitation. Major vessels thrombophlebitis should always be considered, when primary source of septic pulmonary emboli is not clear. This case illustrates the complexity of illness and complications that may arise from a source of infection as the one in this patient. Further therapeutic strategies were tailored accordingly.
Results of chemotherapy in the treatment of chronic lymphoid leukemia in Black Africa: Experience of Côte d’Ivoire
Published on: 27th September, 2019
OCLC Number/Unique Identifier: 8275582880
Background: The treatment of chronic lymphoid leukemia currently uses news drugs which are more expensive in our countries. Its why, the results of chemotherapy remains a challenge in our sector.
Aims: To evaluate the place of polychemotherapy in the treatment of chronic lymphoid leukemia in black Africa.
Methods: It was a prospective, descriptive, analytic and non-comparative study, concerning the records of patients with chronic lymphoid leukemia treated and followed at the department of clinical hematology in Abidjan.
Results: We included 56 patients. The average age was 62 years with extremes of 38 and 84 years. The sex ratio was 0.8 in favor of female. The clinical signs noted a tumor syndrome among which splenomegaly, classified stage III (46, 43%) and adenopathy (64, 29%). Biologically, we observed a blood lymphocytosis (50%), an anemia (39.29%) and a thrombocytopenia (62.50%). The majority of patients were classified stage A of BINET (51.79%). The COP protocol (44.64%) and the monochemotherapy with chlorambucil (39.29%) were the most used. The therapeutic response of polychemotherapy was low (12.5%) compared to 35, 71% for monochemotherapy (p = 0.0001) with overall survival significantly better in monochemotherapy. The outcome of patients used polychemotherapy were more adverse that of patients used chlorambucil alone (p = 0,003). The overall probability of survival at 12 months was 90, 9% for patients who used monochemotherapy and 63, 4% for polychemotherapy.
Conclusion: Polychemotherapy in chronic lymphoid leukemia of black African has an adverse therapeutic response hence the interest of using new therapeutic possibilities.
Different optimization strategies for the optimal control of tumor growth
Published on: 10th December, 2019
OCLC Number/Unique Identifier: 8495685425
In this article different numerical techniques for solving optimal control problems is introduced, the aim of this paper is to achieve the best accuracy for the Optimal Control Problem (OCP) which has the objective of minimizing the size of tumor cells by the end of the treatment. An important aspect is considered, which is, the optimal concentrations of drugs that not affect the patient’s health significantly. To study the behavior of tumor growth, a mathematical model is used to simulate the dynamic behavior of tumors since it is difficult to prototype dynamic behavior of the tumor. A tumor-immune model with four components, namely, tumor cells, active cytotoxic T-cells (CTLs), helper T-cells, and a chemotherapeutic drug is used. Two general categories of optimal control methods which are indirect methods and direct ones based on nonlinear programming solvers and interior point algorithms are compared. Within the direct optimal control techniques, we review three different solutions techniques namely (i) multiple shooting methods, (ii) trapezoidal direct collocation method, (iii) Hermit- Simpson’s collocation method and within the indirect methods we review the Pontryagin’s Maximum principle with both collocation method and the backward forward sweep method. Results show that the direct methods achieved better control than indirect methods.
Vaginal embryonal rhabdomyosarcoma in young woman: A case report and literature review
Published on: 25th May, 2020
OCLC Number/Unique Identifier: 8605988997
Rhabdomyosarcomas are the most common soft tissue tumors of childhood. They are characterized by their poor prognosis. Vaginal location is very rare after puberty and exceptional in the post menopause. Treatment is based on several therapeutic measures combining neoadjuvant chemotherapy followed by surgery and/or external beam radiation therapy. We report herein the case of a 25 years-old woman, presented with vaginal embryonal RMS revealed by metrorrhagia and pelvic pain. The diagnosis was confirmed by biopsy and histopathological study. Pre-treatment workup was negative for metastatic disease. She has received chemotherapy based on vincristine, doxorubicin, and cyclophosphamide. The clinical evolution was marked by improvement of symptoms, unfortunately the patient died following febrile neutropenia after the third cycle of chemotherapy.
Prognostic significance of the Central Tumor Size (CTS) in Cervical Cancer (CC) stages IIb and IIIb: What should we do with the FIGO staging system and therapeutic strategies?
Published on: 17th March, 2021
OCLC Number/Unique Identifier: 8979496954
Cervical cancer constitutes an issue in public health, becoming the leading cause of death by cancer in women between 20-40 years of age in Latin America. In Argentina 5000 new cases are diagnosed each year, where more than 56% are in advanced stages. The aim of the present current opinion or critical review article is to remark the importance of the prognostic significance of the Central Tumor Size in stages IIB and IIIB cervical cancer, as well as to propose a new FIGO Staging System for Cervical cancer and trying to find out a role for the different therapeutic strategies for those cases.
Why? It is the question that I ask myself every day, every hour, every second...
Published on: 22nd March, 2021
OCLC Number/Unique Identifier: 9031334722
It is the dart that penetrates deep into my soul, every time I see with my own eyes how the incidence of cancer has grown in recent years. I am a pathologist. I am dedicated to diagnosing the disease from the cellular and tissue point of view. The answer to the question that haunts me may seem easy, simple, but I am not satisfied with knowing that advances in technology make it possible to diagnose a greater number of entities, many of them in early stages [1]. Of course, this statement is true. However, in recent years we have verified a greater number of cases with aggressive phenotypes, a fact that makes us ask ourselves certain questions. The first one is: Why?
We know that cancer is a multifactorial disease in which genetics and different environmental factors participate. Are we witnessing the concurrence of factors that facilitate the greatest degree of neoplasms? Are habits the cause of this paradigm shift? On the table for debate is the therapeutic success of new strategies, of new drugs, of new algorithms, but the morphology is also changing. This change is exacerbated in the times of pandemic that we have lived through [2]. Pathologists attend a number of cancer diagnoses that have grown exponentially, as has the histological grade, not the staging, of it. And the initial question remains in the air, why?
The fear of going to the hospital, the fear of self-exploration, the diversion of media attention to topics that arouse greater interest ... may be having a harmful effect on the health of patients [3].
I do not tell anything new, at least nothing that cannot be assumed by analyzing what happens every day in this new world, a world that will soon have to face, if not already, a cut in resources, research and other parameters that will negatively influence the answers to the eternal question: Why?
In the era of personalized medicine, the same one that has reached or is close to reaching great milestones in the survival of once-deadly diseases, the microscope shows a parallel reality and allows, at least, to be pessimistic, or at least realistic: suffering…
The management of Irvine-Gass Syndrome in a patient using Inhaler Steroid
Published on: 7th February, 2018
OCLC Number/Unique Identifier: 7355942124
Irvine-Gass syndrome, is one of the most common causes of painless decrease in vision following even uneventful cataract surgery. It usually responds well to medical therapy, but, there are no widely acceptedconsensus on the efficacy of various therapeutic options for the treatment of Irvine-Gass syndrome. The patient presenting in this case report, has systemic hypertension and chronic obstructive pulmonary disease and he use oral anti-hypertension medication and inhaler steroid. He diagnosed as Irvine-Gass syndrome due to presence of decrease in visual acuity and macular edema with hyporeflective cystic intraretinal spaces in optical coherence tomography (OCT) since4th weekcontrol visitfollowing uneventful cataract surgery. After the responsiveness of several medications including topical steroid and non-steroidal anti-inflammatory drugs and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF), intravitreal sustained-release dexamethasone implant was applied. The visual acuity improved to 0.00 logMAR at 1st month after intravitreal dexamethasone therapy and consecutive OCT images showed complete resolution of macular edema with a normalization of the foveal profile.The visual acuity and foveal architecture remained stable in 2-year follow-up period and additional treatment was not needed. To the best of our knowledge, this is the first reportthatmentions the increment of visual acuity after a single dexamethasone implant, even though it did not response anti-VEGF combined with topical steroid and non-steroidal anti-inflammatory drugs.
Transference and countertransference are linked to placebo-nocebo effects and they are an auxiliary resource of unparalleled value in general medicine: Recommendations for general practitioners
Published on: 28th February, 2020
OCLC Number/Unique Identifier: 8541457152
Psychological phenomena of the doctor-patient relationship influence the therapeutic process. Among these phenomena are the transference (the emotions of the patient towards the doctor), and the countertransference (the emotional reactions of the doctor towards the patient). Doctor and patient are within an interactive relationship in a conscious and unconscious way: the patient is influenced by the doctor, and vice versa. Doctor is solely responsible for the control of transference and countertransference, since patients do not have a conscious perception of these phenomena. In general medicine the transference/countertransference have connotations of placebo effect and nocebo. The challenge of the doctor-patient relationship for the doctor is to realize the transference and countertransference phenomena and use them to achieve placebo effects and minimize the nocebo, and also respecting the needs of both parties, so that to improve the quality of clinical practice. Under these conditions, transference and countertransference are auxiliary resources of unparalleled value.
Psychological phenomena in the doctor- Elderly patient relationship
Published on: 8th April, 2020
OCLC Number/Unique Identifier: 8572406620
The doctor-patient communication and the aging of the patients attended by the general practitioner are two important concepts that constantly impact medical consultations. This article raises some reflections and conceptualizations about the main psychological phenomena that have a special importance in the doctor-elderly patient communication and relationship: 1) Stereotypes and prejudices; 2) Regression; 3) Transference, countertransference and resistance; 4) Rapport; 5) Empathy; and 6) Paternalism. The GP must be alert about what affecting the communication with the old man and he should put the means to get a warm relationship. Consequently, to achieve effective communication with an older adult: The GP have to take it easy; to be patient; avoiding stereotypes and prejudices; allowing the patient to establish a benign regressive relationship, until if it is possible due to the biopsychosocial context of the elderly patient, he can begin the non-regressive relationship again; recognizing fact of transference, which put the doctor in another place, is inevitable, but taking into account that it greatly affects his relationship with the patients; avoiding countertransference; considering that the therapeutic alliance or rapport is particularly fragile in elderly patients with chronic diseases; giving greater importance to empathy; knowing that the elderly patient frequently accepts the authority of the doctor, but avoiding falling into an iatrogenic paternalism; and smile.
An exceptional case of bilateral vestibular areflexia complicating acute otitis media
Published on: 2nd July, 2020
OCLC Number/Unique Identifier: 8627247898
Introduction: Bilateral vestibular areflexia is a rare pathological entity whose most frequent etiology is drug ototoxicity. We report an unusual case of bilateral vestibular areflexia complicating acute otitis media through which we raise the difficulties of diagnosis and therapeutic management of this pathology.
Case Report: 57-year-old Tunisian patient who consults for a loss balance associated with earache and hearing loss. Initial clinical examination revealed bilateral acute otitis media with a right harmonious vestibular syndrome and normal neurological examination. The diagnosis of post-otitis labyrinthitis was retained. The patient was put on antibiotics and corticosteroids. The evolution was marked by the persistence of instability in darkness and oscillopsia; vestibular explorations concluded with bilateral vestibular areflexia. MRI concluded to posterior labyrinthitis and eliminated central neurological involvement. The patient was kept under betahistine. The tympanic cavity was drained by a tympanic aerator on both sides. Vestibular rehabilitation was started quickly. Gradual improvement was obtained of autonomy with persistent oscillopsia.
Conclusion: Bilateral vestibular areflexia poses diagnostic problems based on anamnestic and clinical arguments and vestibular explorations. The therapeutic management is delicate, vestibular reeducation occupies a primordial place.
Protecting teeth and gums during rigid endoscopy of the upper aerodigestive tract: Our experience with a disposable, mouldable and rigid thermoplastic mouthguard
Published on: 11th August, 2020
OCLC Number/Unique Identifier: 8650653783
Direct rigid pharyngoscopy, laryngoscopy and oesophagoscopy are very common procedures in the Otolaryngology-Head & Neck department, both for diagnostic and therapeutic purposes. The phayngoscopes, laryngoscopes and oesophagoscopes are solid straight metal instruments to facilitate examination and passage of instruments through them. The process of pharyngo-laryngo-oesophagoscopy invariably involves some contact with the upper dentition resulting in some pressure over the teeth and jaw when suspension laryngoscopy is carried out.
A comparative study of single or dual treatment of theranostic 188Re-Liposome on microRNA expressive profiles of orthotopic human head and neck tumor model
Published on: 25th February, 2021
OCLC Number/Unique Identifier: 8930780806
Background: 188Re-liposome has been used for evaluating the theranostic efficacy on human head and neck squamous cell carcinoma (HNSCC) at preclinical stages. Here we furthercompared the microRNA expressive profile in orthtopic HNSCC tumor model exposed to 188Re-liposome.
Methods: A single dose or dual doses of 188Re-liposome was intravenously injected into tumor-bearing mice followed by the Cerenkov luminescent imaging (CLI) for monitoring the accumulation of 188Re-liposome in tumors. The microRNA expressive profile was generated using the Taqman® OpenArray® Human MicroRNA Panel followed by the DIANA mirPath analysis, KEGG signaling pathways prediction, and Kaplan-Meier survival analysis for predicting the prognostic role of 188Re-liposome affected microRNAs.
Results: Dual doses of 188Re-liposome exhibited a better tumor suppression than a single dose of 188Re-liposome, including reduced tumor size, Ki-67 proliferative marker, and epithelial-mesenchymal transition (EMT) related factors. The microRNA expressive profiles showed that 22 microRNAs and 19 microRNAs were up-regulated and down-regulated by dual doses of 188Re-liposome, respectively. Concomitantly, these two groups of microRNAs were inversely regulated by a single dose of 188Re-liposome accordingly. These microRNAs influenced most downstream genes involved in cancer related signaling pathways. Further, miR-520e and miR-522-3p were down-regulated whereas miR-186-5p and miR-543 were up-regulated by dual doses of 188Re-liposome, and they separately affected most of genes involved in their corresponding pathways with high significance. Additionally, high expressions of miR-520e and miR-522-3p were associated with lower survival rate of HNSCC patients.
Conclusion: MicroRNA expression could be used to evaluate the therapeutic efficacy and regarded prognostic factors using different doses of 188Re-liposome.
Dry eye syndrome: Therapeutic challenges and future trends
Published on: 12th December, 2019
OCLC Number/Unique Identifier: 8500737592
Introduction: Intense Pulsed Light (IPL) is the therapeutic tool implemented in the treatment of dry eye, characterized by the emission of waves of 500-1200nm in the region of the upper and lower eyelids. Dry eye is a recurring complaint in ophthalmology offices and has an impact on the patient’s quality of life. It results from dysfunction of the meibomian glands, duct obstruction, and quantitative and qualitative changes in glandular secretion. It is manifested by dryness and irritation, foreign body sensation, burning, tearing, and eye fatigue. The available treatments are short term palliative with unsatisfactory results.
Psychotropic drugs prescription block the positive effects of the doctor-patient communication and relationship
Published on: 18th February, 2021
OCLC Number/Unique Identifier: 9031343880
The fact that general practitioner (GP) or psychiatrist understands the psychosocial effects of prescribing on the doctor-patient relationship is as important, if not more so, than knowing pharmacology. Any prescription of drugs modifies the doctor-patient relationship. Drugs, especially psychotropic drugs, act on symptoms and change thoughts, feelings, and behaviors; they can create both physical and psychological dependency; they can discourage a deep search for real solutions, both on the part of the doctor and the patient; they can affect the doctor’s access to the patient and the problem will be out of their reach. Psychotropic drugs can make the effect of the doctor in himself as a drug more difficult, favor an insignificant or problematic or little human relational context, where the GP/psychiatrist does not delve into the true meaning of the symptoms, and the patient tends not to get involved, to make an emotional withdrawal, to be passive before the prescribed drug, and can result in the chronification and structuring of functional symptoms that become organic, with lack of cooperation of the doctor and the patient, and paradoxically with over-compliance or therapeutic discontinuity and the lack of pharmacological adherence, absences to appointments or delays or cancellations of visits, and the denial of responsibility of both the doctor and the patient.
Using correlative microscopy for studying and treatment of Mycoplasma infections of the ophtalmic mucosa
Published on: 12th March, 2020
OCLC Number/Unique Identifier: 8553865045
Purpose: We have studied in 18-month 21 patients showing kerato-conjunctivitis and/or dermato-blefaritis, where we will find a constant presence of mycoplasma in SEM optical cytology samples. The 21 patients were divided as follows: 7 allergic, 7 alleged allergic and 7 not-allergic, this division it makes between a clinical approach considering clinical history and symptoms. At the first examination, 16 of the 21 patients had a single or multiple infection in which the main pathogenic element was found to be Mycoplasma; the remaining 7, 4 of them were suspected allergic patients, 2 of it, were allergic subjects with the presence of eosinophils or mast cells.
Material and methods: All the study is constructed on citological optical microscopy and citological electron scanning microscopy (SEM) images for demonstrate the efficacy of the SEM in clinical approach at allergic, not allergic and suspected allergic patients.
Therapeutic treatment and Results: Treatment of the allergic and false allergic patients has made with local somministration of galenic composition with ialuronic acid 3 ml and Tetracycline hydrochloride 30 mg and with low level of cortisone and antisthaminic therapy. This treatment is necessary to eradicate the Mycoplasma infection and counteract toxic action of this pathogen on mucosa.
Discussion: After appropriate therapy we note that allergic patients have a greater predisposition to redundancy in infections in the short period (minimum 20 days), while alleged allergic patients have more prolonged infection periods (between 3 and 5 months), with constant presence at low levels of persistent Mycoplasma. The latter continue to show signs and symptoms similar to allergic patients, but with a negative test for tear IgE and absence of eosinophils and/or mast cells, in the optical and SEM samples displayed.
The Daring of Biosimilars
Published on: 1st May, 2017
OCLC Number/Unique Identifier: 7317653965
The so-called “biotechnological revolution” is changing the structure of the Pharmacopoeia [1]. The space of biological products, previously limited to blood products and vaccines, grew from the introduction of first recombinant therapeutics in the 1980s until attaining a 25% by value of the pharmaceutical market. This share is expected to reach 50% in the coming years. More than 80 biotechnology drugs have entered the market in the last ten years. It is estimated that there are more than 900 biological products on development for more than 100 diseases [2].
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