Effect of CKD-MBD therapies on the gastrointestinal expression of phosphate transporters

Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is prevalent and encompasses biochemical abnormalities, bone alterations, and vascular calcifications. CKD-MBD treatments include phosphate binders and calcimimetics that effectively lower phosphorus and PTH, respectively, but the impact of these treatments on phosphate transporters in the gastrointestinal tract is still unknown. NaPi2B is considered the primary intestinal phosphate transporter. However, NaPi2B inhibition shows limited effectiveness, thus the importance of PIT1 and PIT2 requires further investigation. Methods: We tested the effects phosphate binders (ferric citrate (FC) and calcium gluconate (Ca)) and the calcimimetic KP2326 (KP) in (Cy/+ male rat; CKD) and untreated normal littermates (NL). Treatments lasted 10 weeks until euthanasia at 28 weeks (moderate-to-advanced CKD), where we collected mucosa samples from duodenum, jejunum, and ileum. Blood was collected for biochemistry measurements. Total RNA was isolated, and qPCR performed to assess phosphate transporters expression (NaPi2B, PIT1, PIT2) normalized to b-actin. Results were analyzed via 2-way ANOVA. Results: As expected, CKD had abnormal plasma concentrations of phosphorus, PTH, and FGF23. FC and KP effectively lowered phosphorus. KP and Ca lowered PTH, but Ca increased FGF23. NaPi2B was expressed in the duodenum and jejunum but not in the ileum, and its expression was upregulated with FC compared to NL. PIT1 was expressed in all segments, but the expression was the highest in the ileum, while PIT2 was constitutively expressed in all segments. Ca led to higher PIT1 and PIT2 expression in the duodenum and jejunum compared to NL, CKD, or KP. KP led to higher expression of PIT1 in the ileum compared to CKD, FC, and Ca. Conclusions: CKD-MBD therapies differentially impacted biochemistries and phosphate transporters expression. The effect of Ca on gastrointestinal expression of PIT1 and PIT2 may explain the higher plasma phosphorus and should be further explored.

Association of Serum Copper Levels and Amine Oxidase Copper Gene 1 (AOC1) with Migraineurs

Migraine is a common neurovascular multifactorial disease with biochemical abnormalities in the central nervous system (CNS). It is characterized by episodes of frequent headaches, affecting about 14% of the world's population. Trace elements are essential to play an important role in neurotransmission and causing oxidative stress in patients with migraine. Also, it is hypothesized that Histamine (biogenic amine), catabolized by Diamine oxidase (DAO), induces a vascular headache. DAO contains Copper as a cofactor and is coded by the Amine oxidase copper containing 1 (AOC1) gene. This study aims to determine the level of serum copper (Cu), an association of the AOC1 gene and antioxidant capacity in migraine patients. In this study, a total number of 200 individuals (patients and controls) were equally distributed in each group according to demographic details obtained. The results obtained from this study were found to be significant to migraine. The frequency of T allele (rs10156191) in exon 4 AOC1 was 7.5% in migraineurs OR of 16.13; 95% CI- 0.63 to 47.97, and the p-value was observed to be 0.074. The mean concentration of Cu was found to be 0.09 ± 0.02 mg/L and 0.22 ± 0.10 mg/L in patients and controls, respectively. Antioxidant capacity of serum was found to be lower in patients (3 ± 1.2 μM ascorbic acid equivalents) when compared to controls (7 ± 0.9 μM ascorbic acid equivalents). Decreased Cu and a nonsynonymous of rs10156191 are associated with migraine, which may decrease in DAO activity. Further research, needs to be focused on the DAO activity that can determine the migraine-inducing effect.

Lipid Profile in Thyroid Autoimmunity - A Study among Reproductive Age Group Females of Central Kerala

BACKGROUND One of the most common causes of thyroid dysfunction among women is autoimmunity, especially in fertile age group. Thyroid hormone disorders are associated with a number of biochemical abnormalities including dyslipidaemia, metabolic dysfunctions, spontaneous miscarriage, and preterm delivery. Dyslipidaemia is one of the most common metabolic abnormalities present in patients with thyroid disease. The purpose of this study was to find the association between anti-thyroid peroxidase antibody (anti-TPO) and dyslipidaemia in reproductive age group females from Central Kerala. METHODS A total of 200 asymptomatic women, all in reproductive age group, from a tertiary hospital in Kerala participated in this study. Demographic data and detailed medical history of the participants were collected. Anti-TPO and thyroid stimulating hormone (TSH) were measured using chemiluminescence immunoassay system. Serum lipid profile was estimated using fully automated random-access clinical chemistry analyser EM - 360. Continuous variables were compared between the groups using Mann–Whitney U-test. P value lesser than 0.05 was considered as statistically significant. RESULTS The mean age of the subjects was 32.92 ± 11.82 years. A total of 47 participants (23.5 %) were anti-TPO positive. Abnormality in lipid profile was present in 72.34 % (N = 34) of the anti-TPO positive participants. In the anti-TPO positive group, 51.06 % of the participants had hypercholesterolemia. In the anti-TPO positive group, anti-TPO levels show a statistically significant correlation with total cholesterol and triglyceride levels (P = 0.07 and P < 0.01). A total of 9 % (N = 18) had thyroid stimulating hormone (TSH) values greater than normal range (0.34- 4.25 µIU/mL) suggesting presence of hypothyroidism. TSH values were also significantly associated with lipid profile in the anti-TPO positive group. Both thyroid autoimmunity and dyslipidaemia can affect fertility, pregnancy and other reproductive outcomes. CONCLUSIONS Women should be screened for autoimmune antibodies and associated biochemical abnormalities to estimate and reduce the risk of cardiovascular morbidity, negative pregnancy outcomes and infertility. KEY WORDS Thyroid Autoimmunity, Anti-TPO Antibody, Dyslipidaemia

Severe COVID-19 is associated with sustained biochemical disturbances and prolonged symptomatology; A retrospective single-centre cohort study

IntroductionCoronavirus disease 2019 (COVID-19) is associated with significant acute clinical manifestations, and reports indicate that some patients experience prolonged symptomatology and morbidity. These late clinical manifestations have been termed Post-Acute Sequelae of COVID-19 (PASC) and hypothesised to be associated with clinical severity in the acute infection phase and biochemical abnormalities.AimEvaluate the incidence of PASC in previously hospitalised COVID-19 patients and compare the admission and follow-up levels of biochemical parameters stratified according to baseline clinical severity.MethodsN = 168 COVID-19 patients previously hospitalised at the Zan Mitrev Clinic in Skopje, North Macedonia, with matched laboratory data at baseline and follow-up clinical visit > 30 days post-discharge, were stratified according to National Institute of Health clinical severity guidelines as mild, moderate, severe or critical according to admission clinical presentation. We assessed the incidence of PASC and compared the biochemical profile.ResultsThe median hospitalisation and clinical follow-up period were 11 (9-20) and 53 (30-105) days. The overall incidence of PASC was 56.5% (95/168); most PASC cases were confined to the severe sub-group (61/101, 61.4%). Contrary to mild and moderate cases and a healthy “non-COVID-19” control cohort, we observed that severe COVID-19 cases experienced sustained biochemical disturbances, most notably elevated D-dimers and Ferritin of 600 ng/ml (283-1168) and 432 ng/ml (170-916), respectively.ConclusionsPreviously hospitalised severe COVID-19 patients are more likely to experience Post-Acute Sequelae of COVID-19 and prolonged biochemical disturbances, evident by abnormal values of D-dimers and Ferritin.

Blood biochemical abnormalities of intensive care unit patients with SARS-CoV-2 infection, single center experience in Bangladesh

Background: Since its emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, and led to ever-increasing mortality. SARS-CoV-2 infection perturbs the function of the body’s vital organs, making patients of all ages susceptible to the disease. Nevertheless, individuals developing critical illness with poor outcomes were mostly the elderly and people with co-morbid conditions, who constituted the vast majority of coronavirus disease 2019 (COVID-19) fatalities. Complications of COVID-19 mostly involve the respiratory, renal and cardiovascular systems, and in severe cases secondary infections leading to pneumonia and acute respiratory distress syndrome, which may precede the death of the patient. Multi-organ failure in individuals with COVID-19 could be a consequence of their co-morbidities. It is hoped that the review will lead to more comprehensive understanding of this complex disease. The aim of the study was to evaluate biochemical abnormalities during SARS-CoV-2 infection of ICU patients.Methods:This observational study was conducted in Square Hospital Limited, Dhaka, Bangladesh, on 50 patients received ICU treatment with moderate to severe COVID-19 symptoms admitted to this hospital from 15 July to 15 September 2020.Results: Among the participants most of them were 19 (38%) belongs to 65-74 years age group male 38 (78.00%) were dominating the gender distribution. IL6, CRP, creatinine and troponin were found the most significant in biochemical blood parameters. The maximum level of comorbidity was observed due to diabetes mellitus, ischemic heart disease, and hypertension.Conclusions:Biochemical parameters may be used as an indicator of COVID-19 infections and the severity of ICU patients. For the consistency of the course of patients, the markers could be used.

Cushing’s disease presenting with psychosis

Cushing’s disease is a rare endocrine condition in which a pituitary corticotroph adenoma drives excess adrenal cortisol production, and is one cause of endogenous Cushing’s syndrome. We present a young woman with 3 weeks of headaches and cognitive disturbance who subsequently developed florid psychosis requiring multiple admissions under neurology and psychiatry. Her clinical stigmata of hypercortisolism and biochemical abnormalities prompted an MR scan of the pituitary, which confirmed a pituitary microadenoma. Treatment with metyrapone and subsequent surgery led to complete recovery within 2 months. Cushing’s disease commonly causes neuropsychiatric symptoms and can present with psychosis. Diagnosing Cushing’s disease can be challenging, but with early diagnosis and treatment it has an excellent prognosis.

Clinical Features and Severity of Leptospirosis Cases Reported in the Hawke’s Bay Region of New Zealand

Aims. To record demographics, symptoms, signs, and laboratory features of confirmed leptospirosis cases in the Hawke’s Bay area of New Zealand to aid clinicians in diagnosis and recognition of severity. Methods. Review of suspected leptospirosis cases referred to the reference laboratory from hospitals in the Hawke’s Bay region between March 2003 and March 2012. Inclusion criteria were IgM positivity and diagnosis confirmed with either polymerase chain reaction (PCR) or microscopic agglutination test (MAT). A retrospective systematic review of case notes was completed for demographic and laboratory data. Results. Forty-three cases were included. Most common presenting symptoms were pyrexia (93%), myalgia, and headache (both 86%). 93% of patients worked in the farming or meat industries. The most common biochemical abnormalities were elevated CRP (100%) and abnormal urinalysis (93%). There was no difference in disease severity between icteric and anicteric patients. Compared to other studies, patients in New Zealand have less severe disease. Conclusion. Contrary to popular understanding, this study has not found icteric leptospirosis to be related to more severe disease. Anicteric leptospirosis should be a differential diagnosis in patients presenting with pyrexia, myalgia, and headache who have elevated CRP and abnormal urinalysis.

Tubulopathy meets Sherlock Holmes: biochemical fingerprinting of disorders of altered kidney tubular salt handling

Evolution moves in mysterious ways. Excretion of waste products by glomerular filtration made perfect sense when life evolved in the ocean. Yet, the associated loss of water and solutes became a problem when life moved onto land: a serious design change was needed and this occurred in the form of ever more powerful tubules that attached to the glomerulus. By reabsorbing typically more than 99% of the glomerular filtrate, the tubules not only minimise urinary losses, but, crucially, also maintain homeostasis: tubular reabsorption and secretion are adjusted so as to maintain an overall balance, in which urine volume and composition matches intake and environmental stressors. A whole orchestra of highly specialised tubular transport proteins is involved in this process and dysfunction of one or more of these results in the so-called kidney tubulopathies, characterised by specific patterns of clinical and biochemical abnormalities. In turn, recognition of these patterns helps establish a specific diagnosis and pinpoints the defective transport pathway. In this review, we will discuss these clinical and biochemical “fingerprints” of tubular disorders of salt-handling and how sodium handling affects volume homeostasis but also handling of other solutes.