Journal of Basic and Clinical Physiology and Pharmacology最新文献

Objectives: How gaseous signalling molecules affect ion transport processes contributing to the physiological functions of the gastrointestinal tract under hypoxic conditions still needs to be clarified. The objective of the present study was to characterize the impact of gaseous signalling molecules on parameters of colonic ion transport during a hypoxia/reoxygenation cycle and the remaining secretory capacity of the epithelium after such a cycle.

Methods: Short-circuit current (I_sc) and tissue conductance (G_t) recordings in Ussing chamber experiments were performed on rat colon samples using CORM-2 (putative CO donor; 35 and 350 µM), sodium nitroprusside (NO donor; 100 µM), NaHS (fast H₂S donor; 10 - 1,000 µM), GYY 4137 (slow H₂S donor; 50 µM) and Angeli's salt (HNO donor; 100 µM) as donors for gasotransmitters. Inhibition of endogenous synthesis of H₂S was operated by inhibitors of cystathionin-γ-lyase, i.e. dl-propargylglycine (1 mM) or β-cyano-l-alanine (5 mM), and the inhibitor of cystathionine-β-synthase, amino-oxyacetate (5 mM).

Results: The fast gasotransmitter donors NaHS, sodium nitroprusside and Angeli's salt, administered 5 min before the onset of hypoxia, induced an increase in I_sc. The response to the subsequently applied hypoxia was characterized by a decrease in I_sc, which tended to be reduced only in the presence of the lowest concentration of NaHS (10 µM) tested. Reoxygenation resulted in a slow increase in I_sc, which was unaffected by all donors or inhibitors tested. The stable acetylcholine derivative carbachol (50 µM) was administered at the end of each hypoxia/reoxygenation cycle to test the secretory capacity of the epithelium. Pretreatment of the tissue with the putative CO donor CORM-2 suppressed the secretory response induced by carbachol. The same was observed when cystathionin-γ-lyase and cystathionin-γ-synthase were inhibited simultaneously. Under both conditions, G_t drastically increased suggesting an impaired tissue integrity.

Conclusions: The present results demonstrate that none of the exogenous gasotransmitter releasing drugs significantly ameliorated the changes in epithelial ion transport during the hypoxia/reoxygenation cycle ex vivo. In contrast, the putative CO donor CORM-2 exerted a toxic effect on the epithelium. The endogenous production of H₂S, however, seems to have a protective effect on the mucosal integrity and the epithelial transport functions, which - when inhibited - leads to a loss of the secretory ability of the mucosa. This observation together with the trend for improvement observed with a low concentration of the H₂S donor NaHS suggests a moderate protective role of low concentrations of H₂S under hypoxic conditions.

Liver diseases are complex conditions, significantly influenced by oxidative stress. This comprehensive review assesses the therapeutic role of antioxidants like l-ascorbic acid and α tocopherol, beta-carotene, various minerals, and plant-based ingredients in mitigating oxidative stress-induced liver diseases. The manuscript delves into the critical influence of genetic and epigenetic factors on disease susceptibility, progression, and response to antioxidant therapy. While animal studies suggest antioxidant efficacy in liver disease treatment, human trials remain inconclusive, and caution is advised due to its possible potential pro-oxidant effects. Moreover, the interactions of antioxidants with other drugs necessitate careful consideration in the management of polypharmacy in liver disease patients. The review underscores the need for further research to establish the clinical benefits of antioxidants with understanding of possible antioxidant toxicities to elucidate the intricate interplay of genetic, epigenetic, and environmental factors in liver diseases. The aim is to foster a better understanding of the knowledge on hepatic disease management with judicial antioxidant therapies.

The humanised monoclonal antibody donanemab is being developed to treat early onset Alzheimer's disease (AD). This drug targets N-truncated pyroglutamate amyloid-peptide at position 3 (N3pG), a modified form of deposited amyloid-peptide. The symptoms of Alzheimer's disease include gradual memory loss and other cognitive impairments. This disease is characterized by amyloid plaques, which are formed as a result of an accumulation of amyloid-(A-β) peptides. Despite granting donanemab breakthrough therapy designation in June 2021, the FDA rejected donanemab's accelerated approval application in January 2023, due to inadequate safety data. According to the baseline amyloid level, the time to achieve plaque clearance (amyloid plaque level <24.1 centiloids) varied. Patients with higher baseline levels were more likely to achieve amyloid clearance. The safety of the drug was demonstrated by amyloid-related imaging abnormalities (ARIA), which ranged from 26.1 to 30.5 % in the studies. Clinical trial results have shown that donanemab delays cognitive and functional deterioration in patients with mild to moderate AD. However, it is not yet known whether donenameb offers therapeutic benefits that can change and improve the clinical condition of AD patients. To achieve significant clinical benefits in AD patients with cognitive impairment, further studies may be needed to investigate the interaction between A-β plaque reduction and toxic tau levels.

Objectives: Meckel's diverticulum (MD) is a common asymptomatic congenital intestinal anomaly. Clinical manifestations of MD can occur in about 4 % of cases by the presentation of its complications, generally intestinal occlusion, bleeding, and diverticular inflammation. MD's complications are challenging preoperative diagnoses, as manifest with clinical symptoms that overlap with those of other acute non-traumatic abdominal diseases. Thus, in the emergency setting, abdominal computed tomography (CT) represents an essential tool for the correct diagnosis of complicated MD.

Case presentation: We present a case of a preoperative CT diagnosis of perforated Meckel's diverticulitis in a young patient admitted to our Emergency Department complaining of acute abdominal pain.

Conclusions: The case highlights the importance of evaluating Meckel's diverticulum complications among the differential diagnoses of acute non-traumatic abdominal pain and the high sensitivity of CT in assessing their presence in the proper clinical setting.

Introduction: Phosphodiesterase 5 inhibitors (PDE5-is) are used worldwide as first line therapy for erectile dysfunction (ED). Current literature reported data on the warning association between PDE5-is use and the development of cutaneous melanoma. However, these data are contrasting, thus we aim to summarise evidence regarding this association.

Content: A systematic review of all published articles related to the effects of PDE5-is in the development of cutaneous melanoma was performed. PubMed, EMBASE, and Cochrane library were queried for all the published studies indexed up to the 26th of May 2023. A combination of keywords related to PDE5-is and melanoma were used. Only original studies based on human subjects in the English language were included in the analysis.

Summary and outlook: Of 505 articles identified, only eight original articles were considered for further analysis. Overall, five of the selected articles including 657,984 subjects agrees on an increased risk of developing melanoma in PDE5-is users. On the other hand, three original articles based on data regarding 360,915 subjects, disagree with the previous statement declaring any association between PDE5-i use and melanoma. Current literature still reports contrasting data regarding the association between PDE5-is assumption and increased risk of melanoma, but a possible association is described, bringing attention to higher risk melanoma category of patients. More clinical studies are needed to clarify the impact of PDE5-is in the development and progression of melanoma.

Objectives: Breakfast replenishes glucose homeostasis and provides other micro-nutrients for the normal functioning of the body after a long night at night. Habitually skipping breakfast leads not only to metabolic disturbances but also to neurocognitive impairment. Hence, the current study was carried out to study the effect of skipping breakfast on neurocognitive functions.

Methods: A 9-item breakfast questionnaire was distributed online to students for identifying habitual breakfast skippers from non-skippers based on inclusion criteria. Random blood glucose was noted and visual and auditory reaction time, critical flicker fusion frequency, and Stroop test were assessed in both groups to assess cognition.

Results: Forty one habitual breakfast skippers who met the inclusion criteria showed increased visual reaction time, and auditory reaction time indicating cognitive impairment. A significant reduction in the Stroop test was observed among the non-skipper group when compared to the skipper group.

Conclusions: This study suggests that skipping breakfast diminishes neurocognitive functions like problem-solving, planning, judgment, information retention, and reasoning.

Objectives: Cardiovascular disease (CVD) remains the primary cause of mortality in individuals with type 2 diabetes mellitus. Digital health has quickly emerged as a technology with the ability to bridge the gap in cardiovascular disease self-management and revolutionize the way healthcare has traditionally been delivered. However, there is little data on the application of mobile technologies for cardiovascular risk reduction among diabetic patients. The current study has been constructed with this in mind.

Methods: A framework for the development of a healthy heart mobile application for CVD risk stratification and risk management among Type 2 diabetes mellitus patients was finalized after consultation with diabetologists, nutritionists, and scientists. The mobile app has three user cases: Patient login, doctor login, and admin login. A questionnaire was designed and the feedback of patients and Physicians was taken regarding the design, presentation, content, and user-friendliness of the app based on responses obtained on the questionnaire.

Results: The Android version of the healthy heart mobile mobile app was developed for CVD risk stratification and risk management among type 2 diabetes mellitus patients. The dashboard of the mobile app displayed the CVD risk score and category (mild, moderate, high, or very high CVD risk; which was colored coded), health tracker to monitor medication adherence, lipid profile, diabetes control, CVD risk profile and compliance with the WHO recommendations regarding diet, physical activity and addictions, User acceptability and experience were tested for the developed healthy heart mobile app among patients and physicians. The majority of the respondents graded the design, presentation, content, and user-friendliness of the app as either excellent or good.

Conclusions: The mobile app for self-management and CVD risk reduction among diabetic patients was successfully developed. The paper and mobile-based CVD risk calculation and stratification were found to be a match for all the participants. The app was updated based on suggestions from the pilot study and was well-accepted by both patients and physicians.

Objectives: Graft-versus-host disease (GVHD) of central nervous system is an atypical and rare manifestation of chronic GVHD, presenting with a heterogeneous spectrum of signs and symptoms. Diagnosis of neurological manifestations of GVHD can be highly challenging and remain associated with dismal prognosis, significant morbidity, and reduced quality of life.

Case presentation: In this report, we describe a 39-year-old woman developing neurological signs and symptoms 8 months after allogeneic HSCT magnetic resonance imaging showed multifocal hyperintense lesions involving the periventricular region and frontal subcortical white matter. There was no laboratory evidence of infective or malignant etiology, and the case was diagnosed as CNS-GVHD. The patient was treated with intravenous methylprednisolone pulse therapy and the clinical conditions gradually improved. After few months, patient symptoms progressed despite the addition of high-dose intravenous immunoglobulin, tacrolimus, and a new course of high dose steroids. To engage targeted therapy, the patient underwent brain biopsy that revealed a loss of myelin fibers, perivascular and diffuse infiltration of T cells, and macrophages associated with reactive gliosis, representing a demyelinating disease. We intensified treatment with cyclophosphamide and subsequently introduced ibrutinib as salvage strategy. Despite a magnetic resonance imaging showing great regression of the demyelinating lesions, patient's conditions deteriorated and she died 16 months after HSCT.

Conclusions: CNS-GVHD is a rare complication of HSCT that is difficult to diagnose. Based on our experience, brain biopsy may represent a useful diagnostic tool when the clinical features of neurological symptoms are ambiguous or in patients without evidence of preceding chronic GVHD.

Objectives: This study aimed to assess the efficacy of the 3-day food records in monitoring and enhancing dietary habits among patients with type 2 diabetes mellitus.

Methods: A total of 49 patients with type 2 diabetes mellitus were enrolled, with 38 completing the study. Participants were instructed to record their food intake over 3 consecutive days every 2 months. Key anthropometric and glycometabolic parameters, including body weight, abdominal circumference, glycated hemoglobin, and fasting blood sugar, were evaluated at baseline and after 6 months.

Results: The introduction of the 3-day food records led to significant improvements in body weight, abdominal circumference, glycated hemoglobin, and fasting blood sugar. Additionally, there was a notable increase in the percentage of patients adhering to the LARN nutritional recommendations, especially concerning the intake of carbohydrates, simple sugars, proteins, fiber, and water. However, adherence to lipid and saturated fat recommendations remained a challenge.

Conclusions: The 3-day food records emerges as a valuable tool in the dietary management of patients with type 2 diabetes mellitus. By facilitating real-time monitoring and feedback, it holds promise in enhancing patient adherence to nutritional guidelines, thereby improving key health outcomes.