Recent Advances in Aptasensor for Cytokine Detection: A Review

Cytokines are proteins secreted by immune cells. They promote cell signal transduction and are involved in cell replication, death, and recovery. Cytokines are immune modulators, but their excessive secretion causes uncontrolled inflammation that attacks normal cells. Considering the properties of cytokines, monitoring the secretion of cytokines in vivo is of great value for medical and biological research. In this review, we offer a report on recent studies for cytokine detection, especially studies on aptasensors using aptamers. Aptamers are single strand nucleic acids that form a stable three-dimensional structure and have been receiving attention due to various characteristics such as simple production methods, low molecular weight, and ease of modification while performing a physiological role similar to antibodies.

Activation of Innate Immunity by Therapeutic Nucleic Acids

Nucleic acid-based therapeutics have gained increased attention during recent decades because of their wide range of application prospects. Immunostimulatory nucleic acids represent a promising class of potential drugs for the treatment of tumoral and viral diseases due to their low toxicity and stimulation of the body’s own innate immunity by acting on the natural mechanisms of its activation. The repertoire of nucleic acids that directly interact with the components of the immune system is expanding with the improvement of both analytical methods and methods for the synthesis of nucleic acids and their derivatives. Despite the obvious progress in this area, the problem of delivering therapeutic acids to target cells as well as the unresolved issue of achieving a specific therapeutic effect based on activating the mechanism of interferon and anti-inflammatory cytokine synthesis. Minimizing the undesirable effects of excessive secretion of inflammatory cytokines remains an unsolved task. This review examines recent data on the types of immunostimulatory nucleic acids, the receptors interacting with them, and the mechanisms of immunity activation under the action of these molecules. Finally, data on immunostimulatory nucleic acids in ongoing and completed clinical trials will be summarized.

Vitamin D metabolite and calcium phosphorus metabolism in in patients with primary hyperparathyroidism on the background of bolus therapy with colecalciferol

BACKGROUND: Vitamin D (25-hydroxyvitamin D [25(ОН)D]) deficiency (<20 ng/mL) and insufficiency (20–29 ng/mL) are common in primary hyperparathyroidism (PHPT), but data regarding the vitamin D metabolism in this population is limited.AIM: The aim of this study is to estimate the vitamin D metabolites and their relationship with the main parameters of phosphorus-calcium metabolism in patients with PHPT at baseline and on the background of a single dose of cholecalciferol 150,000 IU.MATERIALS AND METHODS: A single-center interventional, dynamic, prospective, comparative study has been carried out. The study included 54 participants, divided into two groups: the 1st group included 27 patients with confirmed PHPT, the 2nd control group (n = 27), matched on gender (p = 0.062). The study included 4 visits; the baseline laboratory examination and a bolus dose of cholecalciferol were performed at the visit 1, the subsequent visits included a dynamic laboratory examination.RESULTS: Vitamin D deficiency (<20 ng/ml) was detected in 69% of patients with PHPT. In the PHPT group (before cholecalciferol therapy), there was a direct association of 1.25(OH)2 D3 with albumin-corrected and ionized calcium, as well as between the 25(OH)D3 /24.25(OH)2 D3 ratio with PTH and magnesium. After taking of cholecalciferol, the levels of 1.25(OH)2 D3 and 25(OH)D3 /24.25(OH)2 D3 were significantly increased, and the levels of 25(OH)D3 /1.25(OH)2 D3 were significantly declined at all visits among patients with PHPT. The common 25(OH)D level was comparable to the control group, however the levels of 1,25(OH)2 D3 in patients with PHPT were 55% higher at baseline, and after taking of cholecalciferol 150,000 IU. They remained increased by 3–7 days by an additional 23–36%, significantly higher than those in the control group: 44%, 74% and 65%, at visits 2, 3 and 4, respectively (p<0.05). The taking of 150,000 IU cholecalciferol in the PHPT group did not lead to a significant increase in hypercalcemia and hypercalciuria, which indicates the safety of this dose in patients with mild hypercalcemia (albumin corrected calcium <3 mmol/l). None of the study participants experienced any side effects.CONCLUSION: The completely comprehensive assessment of vitamin D metabolites was carried out for the first time in patients with PHPT before and after using a bolus dose of cholecalciferol. The results confirmed the differences of vitamin D metabolism in chronic excessive secretion of PTH compared to control group, which is new data in the pathogenesis of the disease, and can be used to develop optimal regimens for cholecalciferol taking in this population.

Successful treatment of pituitary gigantism

Pituitary gigantism is extremely rare, resulting from excessive secretion of growth hormone (GH) before fusion of epiphysial growth plates. We report a case of a 13-year-old boy, who presented with increased statural growth and headaches since the age of 10 years. On physical examination, his height was 180.7 cm (+3.3 SD) and Tanner stage V. Investigation revealed increased levels of serum age-adjusted and sex-adjusted insulin-like growth factor 1 (IGF-1) and failure of GH suppression during an oral glucose tolerance test (OGTT). MRI of the sellar region revealed a pituitary macroadenoma. He underwent transsphenoidal surgery and histopathological evaluation revealed mammosomatotropic adenoma. Three months after surgery, IGF-1 normalised, nadir GH during OGTT was less than 1 ng/mL and no residual tumour was found on the MRI. Genetic testing identified a mutation in the AIP gene. This case emphasises the importance of early diagnosis of gigantism, as treatment delay increases long-term morbidity.

Subclinical Cushing’s syndrome: lots of questions — little answers

The literature review provides a definition of the essence of subclinical Cushing’s syndrome. Subclinical Cushing’s syndrome (subclinical hypercortisolism) is a pathological condition of the body characterized by an autonomous, excessive secretion of glucocorticoids, most often an adrenal cortex adenoma, suppression of the adrenocorticotropic function of the pituitary gland and the functional state of the opposite adrenal gland. Such a condition may be clini-cally asymptomatic or be accompanied by some nonspecific signs of hypercortisolism (arterial hypertension, diabetes mellitus, obesity, osteoporosis). Noteworthy is the large variability in the frequency of its detection, which is possibly due to the use of various criteria for assigning individual cases to this category. As a basic screening test for the detection of subclinical hypercortisolism, most researchers consider the most acceptable and effective night suppressive test with 1.0 mg of dexamethasone. Modern tactical and technical approaches to the treatment of subclinical Cushing’s syndrome are quite diverse and are more often based on pragmatic principles than on reliably substantiated ones. The author raises the question: could subclinical Cushing’s syndrome be the result of hyperfunction of normal or diffusely enlarged (hyperplastic) adrenal glands as a result of some disturbances in the hypothalamic-pituitary-adrenal hierarchy. And, finally, are the disorders “accompanying” subclinical Cushing’s syndrome a consequence of the overproduction of cortisol, although often insignificant, or can they be the cause of the onset of subclinical hypercortisolism? For the treatment of subclinical hypercortisolism, adrenalectomy is currently proposed, with the aim of reducing the intake of excessive amounts of glucocorticoids into the patient’s body, leading to the development of these disorders. Known drug methods of suppressing the function of the adrenal cortex — drugs chloditan, mitotane, ketoconazole.

Prevalence of comorbidities among patients with Acromegaly

Background and Objective: Acromegaly is a chronic disorder resulting from excessive secretion of growth hormone and (GH) and insulin-like growth factor 1 (IGF-1) and is associated with several comorbidities. These complications contribute significantly to morbidity and mortality associated with this condition thus early diagnosis leads to better outcomes. There have been studies in other countries to assess the comorbidities associated with acromegaly. However, we do not have any recent data with regards to Pakistan. So, in order to demonstrate the prevalence of demographics, hormonal disorders, and other complications associated with acromegaly we conducted this study. Methods: It is a retrospective review of patients’ records presented to the tertiary care Hospital, Karachi, Pakistan for the diagnosis and management of acromegaly and the complications associated with this condition between the time periods 2000 till 2020. A total of 89 patients fulfilled the inclusion criteria of acromegaly and were included in the study. Comorbid conditions were described based on current guidelines. Patient baseline characteristics were recorded along with other complications arising during treatment. Results: Eighty-nine patients were included. 64% were male, over 70% were older than 30 years old and more than 40% of patients had BMI greater than 30. HTN, pre-hypertension, and CCF were reported in 35.95%, 3.37%, and 6.74%. Diabetes mellitus, hypocortisolism, hypothyroidism, hypogonadism, and hyperprolactinemia were reported in 39.32%, 38.20%, 37.07%, 34.46%, and 16.85% of cases. The prevalence of osteoarthritis, blood disorder, skin changes, thyroid cancer, and spinal stenosis was found out to be around 1.12% each. Conclusions: Acromegaly is associated with cardiovascular and endocrinal disorders. Screening for these disorders at the time of diagnosis can lead to early management and better outcomes translating into decreased mortality. doi: https://doi.org/10.12669/pjms.37.7.4277 How to cite this:Khan SA, Ram N, Masood MQ, Islam N. Prevalence of comorbidities among patients with Acromegaly. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4277 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Emerging Place of JAK Inhibitors in the Treatment of Inborn Errors of Immunity

Among inborn errors of immunity (IEIs), some conditions are characterized by inflammation and autoimmunity at the front line and are particularly challenging to treat. Monogenic diseases associated with gain-of-function mutations in genes critical for cytokine signaling through the JAK-STAT pathway belong to this group. These conditions represent good candidates for treatment with JAK inhibitors. Type I interferonopathies, a group of recently identified monogenic auto-inflammatory diseases characterized by excessive secretion of type I IFN, are also good candidates with growing experiences reported in the literature. However, many questions remain regarding the choice of the drug, the dose (in particular in children), the efficacy on the various manifestations, the monitoring of the treatment, and the management of potent side effects in particular in patients with infectious susceptibility. This review will summarize the current experiences reported and will highlight the unmet needs.

The clinical practice guidelines for primary hyperparathyroidism, short version

Primary hyperparathyroidism (PHPT) is an endocrine disorder of parathyroid glands characterized by excessive secretion of parathyroid hormone (PTH) with an upper normal or elevated blood calcium level. Classical PHPT refers to a symptomatic, multi-system disorder, wich can lead to a significant decrease in the quality of life, disability of patients, and even an increased risk of premature death. Hypercalcemia and the catabolic effect of PTH on various cells are considered as the main pathogenetic mechanisms of the PHPT associated complications. In the last two decades, there has been an increase in the incidence of PHPT, mainly due to the mild forms of the disease, primarily due to the routine calcium screening in North America, Western Europe and, Asia. High prevalence of the disease, as well as the variety of clinical manifestations, cause the attention of different specialists - physicians, rheumatologists, urologists, nephrologists, cardiologists and other doctors. This review cover the main issues of Russian guidelines for the management of PHPT, approved in 2020, including laboratory and instrumental methods, differential diagnosis, surgical and conservative approach, short-term and long-term follow-up. This guidelines also include the recommendations for special groups of patients with hereditary forms of PHPT, parathyroid carcinoma, PHPT during pregnancy.

Glycogen Synthase Kinase-3: A Focal Point for Advancing Pathogenic Inflammation in Depression

Increasing evidence indicates that the host immune response has a monumental role in the etiology of major depressive disorder (MDD), motivating the development of the inflammatory hypothesis of depression. Central to the involvement of chronic inflammation in MDD is a wide range of signaling deficits induced by the excessive secretion of pro-inflammatory cytokines and imbalanced T cell differentiation. Such signaling deficits include the glutamatergic, cholinergic, insulin, and neurotrophin systems, which work in concert to initiate and advance the neuropathology. Fundamental to the communication between such systems is the protein kinase glycogen synthase kinase-3 (GSK-3), a multifaceted protein critically linked to the etiology of MDD and an emerging target to treat pathogenic inflammation. Here, a consolidated overview of the widespread multi-system involvement of GSK-3 in contributing to the neuropathology of MDD will be discussed, with the feed-forward mechanistic links between all major neuronal signaling pathways highlighted.