scholarly journals Acute Intermittent Porphyria: An Overview of Therapy Developments and Future Perspectives Focusing on Stabilisation of HMBS and Proteostasis Regulators

2021 ◽  
Vol 22 (2) ◽  
pp. 675
Author(s):  
Helene J. Bustad ◽  
Juha P. Kallio ◽  
Marta Vorland ◽  
Valeria Fiorentino ◽  
Sverre Sandberg ◽  
...  
Keyword(s):  
Psychiatric Symptoms ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Acute Intermittent Porphyria ◽  
Hormonal Changes ◽  
Inherited Disease ◽  
Therapeutic Approaches ◽  
Symptomatic Disease ◽  
Enzyme Functionality

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease with low clinical penetrance, caused by mutations in the hydroxymethylbilane synthase (HMBS) gene, which encodes the third enzyme in the haem biosynthesis pathway. In susceptible HMBS mutation carriers, triggering factors such as hormonal changes and commonly used drugs induce an overproduction and accumulation of toxic haem precursors in the liver. Clinically, this presents as acute attacks characterised by severe abdominal pain and a wide array of neurological and psychiatric symptoms, and, in the long-term setting, the development of primary liver cancer, hypertension and kidney failure. Treatment options are few, and therapies preventing the development of symptomatic disease and long-term complications are non-existent. Here, we provide an overview of the disorder and treatments already in use in clinical practice, in addition to other therapies under development or in the pipeline. We also introduce the pathomechanistic effects of HMBS mutations, and present and discuss emerging therapeutic options based on HMBS stabilisation and the regulation of proteostasis. These are novel mechanistic therapeutic approaches with the potential of prophylactic correction of the disease by totally or partially recovering the enzyme functionality. The present scenario appears promising for upcoming patient-tailored interventions in AIP.

Sexual Dysfunction in Men Receiving Methadone Maintenance Treatment: Clinical History and Psychobiological Correlates

2015 ◽  
Vol 22 (3) ◽  
pp. 163-175 ◽  
Author(s):  
Gilberto Gerra ◽  
Matteo Manfredini ◽  
Lorenzo Somaini ◽  
Icro Maremmani ◽  
Claudio Leonardi ◽  
...  
Keyword(s):  
Sexual Dysfunction ◽  
Maintenance Treatment ◽  
Methadone Maintenance ◽  
Psychiatric Symptoms ◽  
Clinical History ◽  
Hormonal Changes ◽  
Opioid Agonist ◽  
Healthy Control ◽  
Methadone Patients

Abstract: A variety of studies evidenced a relationship between drug use disorders and sexual dysfunction. In particular, heroin and opioid agonist medications to treat heroin dependence have been found to be associated with erectile dysfunction and reduced libido. Controversial findings also indicate the possibility of factors other than the pharmacological effects of opioid drugs concurring to sexual dysfunction. With the present study, we investigated the link between sexual dysfunction and long-term exposure to opioid receptor stimulation (heroin dependence, methadone maintenance treatment, methadone dosage), the potentially related hormonal changes reflecting hypothalamus-pituitary-gonadal axis function and prolactin (PRL) pituitary release, the role of adverse childhood experiences in the clinical history and the concomitant symptoms of comorbid mental health disorders in contributing to sexual problems. Forty male patients participating in a long-term methadone treatment program were included in the present study and compared with 40 healthy control subjects who never used drugs nor abused alcohol. All patients and controls were submitted to the Arizona Sexual Experiences Scale (ASEX), Child Experiences of Care and Abuse-Questionnaire (CECA-Q) and the Symptom Check List-90 Scale. A blood sample for testosterone and PRL assays was collected. Methadone dosages were recorded among heroin-dependent patients on maintenance treatment. Methadone patients scored significantly higher than controls on the 5-item rating ASEX scale, on CECA-Q and on Symptoms Check List 90 (SCL 90) scale. Testosterone plasma levels were significantly lower and PRL levels significantly higher in methadone patients with respect to the healthy control group. ASEX scores reflecting sexual dysfunction were directly and significantly correlated with CECA-Q neglect scores and SCL 90 psychiatric symptoms total score. The linear regression model, when applied only to addicted patients, showed that methadone dosages were not significantly correlated with sexual dysfunction scores except for ‘erectile dysfunction', for which an inverse association was evidenced. Testosterone values showed a significant inverse correlation with ASEX sexual dysfunction scores, CECA-Q neglect scores and psychiatric symptom at SCL 90 among methadone patients. PRL levels were directly and significantly correlated with sexual dysfunction scores, psychiatric symptoms at SCL 90 and CECA-Q neglect scores. Both testosterone and PRL did not correlate with methadone dosages. The present findings appear to support the view of childhood adversities and comorbid psychiatric symptoms contributing to sexual dysfunction and related hormonal changes among methadone patients, challenging the assumption that attributes sexual problems entirely to the direct pharmacological effects of opioid agonist medications.

scholarly journals New Therapeutic Approaches for Allergy: A Review of Cell Therapy and Bio- or Nano-Material-Based Strategies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2149
Author(s):  
Juan L. Paris ◽  
Paz de la Torre ◽  
Ana I. Flores
Keyword(s):  
Cell Therapy ◽  
Treatment Options ◽  
Allergic Diseases ◽  
Immunological Tolerance ◽  
Term Treatment ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Long Term Treatment ◽  
Nano Material

Allergy constitutes a major health issue due to its large prevalence. The established therapeutic approaches (allergen avoidance, antihistamines, and corticosteroids) do not address the underlying causes of the pathology, highlighting the need for other long-term treatment options. Antigen-specific immunotherapy enables the long-term control of allergic diseases by promoting immunological tolerance to the allergen. However, efficacious immunotherapies are not available for all possible allergens, and the risk of undesired reactions during therapy remains a concern, especially in patients with severe allergic reactions. In this context, two types of therapeutic strategies appear especially promising for the future in the context of allergy: cell therapy and bio- or nano-material-based therapy. In this review, the main strategies developed this far in these two types of strategies are discussed, with several examples illustrating the different approaches.

scholarly journals Health impact of acute intermittent porphyria in latent and non-recurrent attacks patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Juan Buendía-Martínez ◽  
María Barreda-Sánchez ◽  
Lidya Rodríguez-Peña ◽  
María Juliana Ballesta-Martínez ◽  
Vanesa López-González ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Acute Intermittent Porphyria ◽  
Abdominal Ultrasound ◽  
Health Impact ◽  
Symptomatic Disease ◽  
Related Quality ◽  
Biochemical Analyses ◽  
The Impact

Abstract Background Acute intermittent porphyria (AIP) is a genetic disease characterized by acute neurovisceral attacks. Long-term clinical conditions, chronic symptoms and impaired health related quality of life (HRQoL) have been reported during non-attack periods but mainly in patients with recurrent attacks. Our aim was to investigate these aspects in sporadic AIP (SA-AIP) and latent AIP (L-AIP) patients. Fifty-five participants, 27 SA-AIP (< 4 attacks/year) and 28 L-AIP patients with a prevalent founder mutation from Spain were included. Medical records were reviewed, and individual interviews, physical examinations, biochemical analyses, and abdominal ultrasound scans were conducted. HRQoL was assessed through an EQ-5D-5L questionnaire. A comparative study was made between SA-AIP and L-AIP patients. Results The earliest long-term clinical condition associated with SA-AIP was chronic kidney disease. Chronic symptoms were reported in 85.2 % of SA-AIP and 46.4 % of L-AIP patients. Unspecific abdominal pain, fatigue, muscle pain and insomnia were significantly more frequent in SA-AIP than in L-AIP patients. The EQ-5D-5L index was lower in SA-AIP (0.809 vs. 0.926, p = 0.0497), and the impact of “pain”, “anxiety-depression” and “mobility” was more intense in the EQ-5D-5L domains in SA-AIP than in L-AIP subjects and the general Spanish population. Conclusions AIP remains a chronically symptomatic disease that adversely affects health and quality of life, even in patients with low rate of acute attacks. We suggest a regular monitoring of patients with symptomatic AIP regardless of their attack rate or the time since their last attack, with proper pain management and careful attention to kidney function.

scholarly journals How I treat MALT lymphoma: ‘a subjective interpretation of the gospel according to Isaacson….’

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000812
Author(s):  
Markus Raderer ◽  
Barbara Kiesewetter
Keyword(s):  
Malt Lymphoma ◽  
Treatment Options ◽  
B Cell Lymphoma ◽  
Individual Treatment ◽  
Gastric Malt Lymphoma ◽  
Symptomatic Disease ◽  
Chronic Antigenic Stimulation ◽  
First Line Therapy ◽  
Anti Cd20

Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) is an indolent B-cell lymphoma characterised by a fascinating interplay between chronic antigenic stimulation, an immune response insufficient for elimination of the antigen and a mucosal ‘battleground’. The archetype of this association is infection of the gastric mucosa with Helicobacter pylori (HP): a single course of antibiotic HP-eradication treatment may result in long-term remission in up to 80% of patients and is the gold standard for first-line therapy of HP-associated gastric MALT lymphoma. In extragastric or disseminated disease, treatment options range from wait and see in asymptomatic individuals to radiotherapy in localised stages, anti-CD20-antibodies in patients with low symptomatic burden and chemotherapy-based treatment or radio-immunotherapy in symptomatic disease. In addition, more refined immunomodulatory strategies beyond simple eradication of bacteria such as long-term use of the macrolide clarithromycin or the immunomodulatory drug lenalidomide are active. In view of the indolent clinical course, the least toxic individual treatment should be chosen in a disease usually not influencing overall survival in affected patients.

Dyskinesia - Advances in the Understanding of Pathophysiology and Possible Treatment Options

2010 ◽  
Vol 5 (2) ◽  
pp. 34 ◽  
Author(s):  
Hanna S Lindgren ◽  
M Angela Cenci ◽  
Emma L Lane ◽  
◽  
◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Treatment Options ◽  
Primary Role ◽  
Therapeutic Approaches ◽  
Abnormal Involuntary Movements ◽  
Treatment Alternatives ◽  
Novel Therapeutic

The degeneration of nigrostriatal dopaminergic neurons in Parkinson’s disease gives rise to tremor and slowness of movement, cardinal motor symptoms of the disease that can be alleviated by the dopamine precursor L-DOPA. Despite this, long-term L-DOPA treatment is hampered by the development of abnormal involuntary movements, i.e. dyskinesia, in the majority of patients. The pathophysiology of dyskinesia is complex and multifactorial, but excessive swings in extracellular dopamine causing aberrant plasticity in dopaminoceptive neurons are attributed a primary role. To date there are few effective treatment alternatives for patients with Parkinson’s disease experiencing dyskinesia, representing an unmet therapeutic need in the treatment strategy of the disease. This article reviews recent findings from both clinical and pre-clinical studies and their impact on the search for novel therapeutic approaches to levodopa-induced dyskinesia.

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

2015 ◽  
Vol 156 (45) ◽  
pp. 1824-1833 ◽  
Author(s):  
Árpád Illés ◽  
Ádám Jóna ◽  
Zsófia Simon ◽  
Miklós Udvardy ◽  
Zsófia Miltényi
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Novel Treatment ◽  
Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

Hashimoto encephalopathy

2013 ◽  
Vol 154 (33) ◽  
pp. 1312-1316 ◽  
Author(s):  
Gábor Pocsay ◽  
Andrea Gazdag ◽  
József Engelhardt ◽  
István Szaniszló ◽  
Zoltán Szolnoki ◽  
...  
Keyword(s):  
Psychiatric Symptoms ◽  
Immunosuppressive Treatment ◽  
Unknown Origin ◽  
Corticosteroid Treatment ◽  
Thyroid Peroxidase ◽  
Thyroid Autoantibodies ◽  
Thyroglobulin Antibodies ◽  
Hashimoto Encephalopathy ◽  
Generalized Seizures

The authors present a case report and review the literature on Hashimoto encephalopathy. The onset of the disease may be marked by focal and then progressively generalized seizures or other neurological symptoms, but a cognitive decline or various psychiatric symptoms may also emerge. High levels of anti-thyroid peroxidase antibodies and/or anti-thyroglobulin antibodies are present in the serum. Corticosteroid treatment usually results in an improvement of symptoms. The syndrome is frequently overlooked and, therefore, the authors strongly recommend testing serum thyroid autoantibodies in cases with encephalopathy of unknown origin independently on the presence of thyroid disease in the patient or family history. The importance of long-term immunosuppressive treatment should also be stressed. Orv. Hetil., 2013, 154, 1312–1316.

Antiretroviral Treatment-Associated Labia Majora Lipohypertrophy: A Rare Case and Plastic Surgical Treatment Options

2017 ◽  
Vol 2 (1) ◽  
pp. 43
Author(s):  
Akmal Hisham ◽  
Devananthan Ilenghoven ◽  
Wan Syazli Wan Ahmad Kamal ◽  
Salina Ibrahim ◽  
Shah Jumaat Mohd Yussof
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Daily Living ◽  
Treatment Options ◽  
Hiv Positive ◽  
Highly Active ◽  
Labia Majora ◽  
The Face ◽  
Central Fat

The emergence of highly active antiretroviral therapy (HAART) has revolutionized the prognosis of HIV-infected patients. However, the extended use of HAART is associated with a disfiguring complication termed lipodystrophy, a disorder of body fat maldistribution causing peripheral fat loss (lipoatrophy) and central fat accumulation (lipohypertrophy). Lipoatrophy commonly affects the face, legs, buttocks and arm, whilst lipohypertrophy frequently favours the abdomen, breast and dorsocervical region. To our knowledge, we present only the second documented case in the literature of a labia majora lipohypertrophy in a HIV-positive patient receiving long-term HAART. The severity of labial abnormality caused significant physical and functional morbidities. Labiaplasty with dermolipectomy of the labia majora and excisional lipectomy of the mons pubis was successfully performed. At a 6-month follow-up, patient had no recurrence with resolution of symptoms and resumption of normal activities of daily living (ADL).

Considering a Potential Role of Linalool as a Mood Stabilizer for Bipolar Disorder

2020 ◽  
Vol 26 (40) ◽  
pp. 5128-5133
Author(s):  
Kate Levenberg ◽  
Wade Edris ◽  
Martha Levine ◽  
Daniel R. George
Keyword(s):  
Bipolar Disorder ◽  
Treatment Options ◽  
Mood Stabilizer ◽  
Well Being ◽  
Epidemiologic Studies ◽  
Treatment Regimens ◽  
Bipolar Spectrum Disorders ◽  
Short And Long Term

Epidemiologic studies suggest that the lifetime prevalence of bipolar spectrum disorders ranges from 2.8 to 6.5 percent of the population. To decrease morbidity and mortality associated with disease progression, pharmacologic intervention is indicated for the majority of these patients. While a number of effective treatment regimens exist, many conventional medications have significant side effect profiles that adversely impact patients’ short and long-term well-being. It is thus important to continue advancing and improving therapeutic options available to patients. This paper reviews the limitations of current treatments and examines the chemical compound Linalool, an alcohol found in many plant species, that may serve as an effective mood stabilizer. While relatively little is known about Linalool and bipolar disorder, the compound has been shown to have antiepileptic, anti-inflammatory, anxiolytic, anti-depressive, and neurotrophic effects, with mechanisms that are comparable to current bipolar disorder treatment options.

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