Fragile X syndrome - insight into what we know and prospects

Fragile X syndrome is a dominantly inherited genetic disease and is a consequence of the FMR1 gene mutation located on the X chromosome. The number of patients affected by this disease with full mutation is estimated at 1 in 4000 men and 1 in 8000 women, however, the number of carriers with premutation is far greater. Depending on the mutation of the FMR1 gene and levels of its products FMRP a variety of symptoms can be observed including- intellectual disability, mental retardation, lowered behavioral adaptation, autism, and dysmorphic features such as a long face with a broad forehead and prominent ears. The treatment is mostly symptomatic- managing comorbidities and an emphasis on psychological therapy. The objective of this paper is to sum up the most up-to-date knowledge regarding the pathogenesis, treatment- current and clinically tested, and novelties in the Fragile X syndrom

TINU syndrome - literature review

Introduction Tubulointerstitial nephritis with uveitis (TINU syndrome) is a rare condition which mainly affects young females. The pathomechanism of the TINU has not been still well understood but autoimmune background is suspected. Although it was first described in 1975, less than 600 cases have been reported so far. Aim of the study The aim of the study is to present the current knowledge about the TINU syndrome. Material and methods The article was created based on the PubMed database. Articles were searched in English using the following keywords: TINU syndrome, tubulointerstitial nephritis, uveitis. Results TINU syndrome occurs in 0.1-2% of patients with uveitis with no ethnic preferences. It has been linked to a number of potential causes including infectious, genetic, and jatrogenic factors. Clinical manifestation is often atypical what leads to underdiagnosis of disease. There are currently no established specific guidelines on the basis of which a diagnosis of TINU syndrome can be made. Therapy includes topical treatment and systemic corticosteroid therapy. The overall prognosis for patients is favorable, but it is possible to develop chronic kidney disease especially in adults. Summary: TINU syndrome remains a poorly understood disease and is often not taken into account in the diagnostic process. The lack of general treatment standards means that therapy is not always effective. Further research is needed to establish guidelines for the management of this disease

Gastroesophageal Reflux Disease: diagnosis and treatment

Introduction and purpose of the work: The mechanism of gastroesophageal reflux disease depends on reflux of gastric contents into the esophagus as a result of reduced tone of the lower esophageal sphincter. It presents itself in the form of symptoms coming from the esophagus, e.g. heartburn, as well as from outside of it. The aim of this paper is to collect and present current knowledge on gastroesophageal reflux disease as well as diagnosis and treatment through a review of the available literature.    Brief description of the state of the art:  Gastroesophageal reflux disease affects 18.1 - 27.8% of the US population and 8.8 - 25.9% of the European population. It is defined as the presence of troublesome symptoms or complications of reflux of gastric contents into the esophagus. The etiology consists of many factors, such as improper diet, and low physical activity. The disease can manifest itself with symptoms from and outside the esophagus. Diagnosis is based primarily on the history, and in the presence of typical symptoms, therapy with proton pump inhibitors is initiated. Endoscopy and reflux measurement is used when there is no response to pharmacotherapy. The basic drugs are proton pump inhibitors, other drugs are complementary to the basic therapy. A lifestyle change is also recommended. Surgical treatment is an alternative, but it may not be a permanent solution. Other treatments include endoscopic incisionless fundoplication and radiofrequency treatment of the lower esophageal sphincter.    Summary:  Diagnosis of gastroesophageal reflux disease begins with an interview with the patient and empirical pharmacotherapy. If treatment is ineffective, endoscopy and pH measurement are performed. Proton pump inhibitors are the most effective drugs in the treatment of the disease, other drugs are used as a supplement. Surgical and endoscopic procedures are an alternative to chronic pharmacotherapy

Alpha1_{1}-adrenergic receptor blockade in the ventral tegmental area attenuates acquisition of cocaine-induced pavlovian associative learning

Activity of the alpha1-adrenergic receptor (α1-AR) in the ventral tegmental area (VTA) modulates dopaminergic activity, implying its modulatory role in the behavioral functions of the dopamine (DA) system. Indeed, intra-VTA α1-AR blockade attenuates conditioned stimulus dependent behaviors such as drug seeking responses signifying a role of the noradrenergic signaling in the VTA in conditioned behaviors. Importantly, the role of the VTA α1-AR activity in Pavlovian associative learning with positive outcomes remains unknown. Here, we aimed to examine how intra-VTA α1-AR blockade affects acquisition of cocaine-induced Pavlovian associative learning in the conditioned place preference (CPP) paradigm. The impact of α1-AR blockade on cocainereinforced operant responding and cocaine-evoked ultrasonic vocalizations (USVs) was also studied. In addition, both α1-AR immunoreactivity in the VTA and its role in phasic DA release in the nucleus accumbens (NAc) were assessed. We demonstrated cellular localization of α1-AR expression in the VTA, providing a neuroanatomical substrate for the α1-AR echanism. We showed that prazosin (α1-AR selective antagonist; 1 µg/0.5 µl) microinfusion attenuated electrically evoked DA transients in the NAc and dose-dependently (0.1–1 µg/0.5 µl) prevented the acquisition of cocaine CPP but did not affect cocaine-reinforced operant responding nor cocaine-induced positive affective state (measured as USVs). We propose that the VTA α1-AR signaling is necessary for the acquisition of Pavlovian associative learning but does not encode hedonic value. Thus, α1-AR signaling in the VTA might underlie salience encoding of environmental stimuli and reflect an ability of erting/orienting functions, originating from bottom-up information processing to guide behaviors

Osilodrostat therapy in a 26-year-old patient after ineffective surgical treatment of Cushing Disease: a case report

Cushing’s Disease is caused by pituitary adenoma which produces adrenocorticotropic hormone causing hypercortisolemia. First-line treatment involves operative removal of the tumor, however, in some patients it proves ineffective. In those cases, pharmacological treatment is necessary as untreated Cushing’s Disease may be lethal. In 2020 a new steroidogenesis inhibitor – Osilodrostat - was approved by the European Medicines Agency and can be used in the treatment of patients who cannot undergo pituitary surgery or whose previous surgical treatment proved ineffective. We present a case of a 26-year-old female patient who was diagnosed with endogenous Cushing’s Disease and underwent two consecutive operations to remove the tumor - both were ineffective. With deteriorating laboratory results and other pharmacological treatments exhausted Osilodrostat therapy was introduced. Osilodrostat is becoming an important drug in patients with Cushing’s Disease refractory to other treatments

Wieloletnie przeżycie chorych z glejakiem wielopostaciowym — opisy przypadków

Glejak wielopostaciowy należy do pierwotnych nowotworów ośrodkowego układu nerwowego o bardzo dużym stopniu złośliwości. Czas przeżycia od rozpoznania u większości chorych wynosi jedynie kilkanaście miesięcy, a mediana przeżycia około 12 miesięcy. Jedynie 3–8% chorych żyje dłużej niż 3 lata. W pracy opisano przypadki młodego mężczyzny oraz kobiety z rozpoznaniem glejaka wielopostaciowego, którzy żyją odpowiednio 56 i 69 miesięcy. Na podstawie przeglądu piśmiennictwa podjęto próbę zestawienia czynników związanych z lepszym rokowaniem i dłuższym przeżyciem chorych na glejaka wielopostaciowego

Fragile X syndrome - insight into what we know and prospects

Fragile X syndrome is a dominantly inherited genetic disease and is a consequence of the FMR1 gene mutation located on the X chromosome. The number of patients affected by this disease with full mutation is estimated at 1 in 4000 men and 1 in 8000 women, however, the number of carriers with premutation is far greater. Depending on the mutation of the FMR1 gene and levels of its products FMRP a variety of symptoms can be observed including- intellectual disability, mental retardation, lowered behavioral adaptation, autism, and dysmorphic features such as a long face with a broad forehead and prominent ears. The treatment is mostly symptomatic- managing comorbidities and an emphasis on psychological therapy. The objective of this paper is to sum up the most up-to-date knowledge regarding the pathogenesis, treatment- current and clinically tested, and novelties in the Fragile X syndrom

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort