MECHANISMS OF HYPOPHOSPHATAEMIA IN ALCOHOLIC PATIENTS

The aim of our study was to determine the possible pathophysiological mechanisms of hypophosphataemia in a group of 127 patients admitted to hospital for alcohol-related causes. Blood and fresh urine specimens were taken to determine acid-base and electrolyte parameters. Thirty-seven patients (29.1%) had hypophosphataemia (serum phosphorus <0.77 mmol/l) with a range of serum phosphorus of 0.32-0.74 mmol/l. In 17 hypophosphataemic patients inappropriate phosphaturia (FEP04 >20%, TmPO₄/GFR<0.80 mmol/l) was evident, possibly due to hypomagnesaemia, metabolic acidosis, metabolic alkalosis, or a proximal tubular defect in phosphate transport. The causes of hypophosphataemia in the remaining 20 patients were alcohol withdrawal syndrome, respiratory alkalosis and diarrhoea. Patients with hypophosphataemia were more often found to have hypomagnesaemia and respiratory alkalosis than normophosphataemic patients. In conclusion, hypophosphataemia is frequently observed in alcoholic patients due to various pathophysiological mechanisms, such as inappropriate phosphaturia, increased phosphorus entry into cells and increased gastrointestinal loss of phosphate.     

Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.     

Mechanisms of deaths in captive juvenile New Zealand fur seals (Arctocephalus forsteri)

Juvenile seals are sometimes encountered in waters around South Australia with injuries and/or diseases that require veterinary treatment. Two cases are reported where apparently stable animals died soon after being rescued due to quite disparate conditions. In Case 1 a juvenile male New Zealand fur seal (Arctocephalus forsteri) was found unexpectedly dead in its enclosure. A necropsy examination revealed an emaciated juvenile male with no injuries. The intestine was filled throughout its length with melena stool that was due to heavy infestation of the stomach with roundworms with adjacent gastritis. Death was due to shock from upper gastrointestinal blood loss secondary to parasitosis. In Case 2 a second juvenile male New Zealand fur seal (Arctocephalus forsteri) also died unexpectedly in its enclosure. It had been listless with loud respirations since capture. At necropsy there was no blood around the head, neck or mouth, and no acute external injuries were identified. An area of induration was, however, present over the snout with fragmentation of underlying bones. The maxilla was freely mobile and CT scanning revealed multiple comminuted fractures of the adjacent facial skeleton. Examination of the defleshed skull showed fragmentation of the facial skeleton with roughening of bones in keeping with osteomyelitis. Death was attributed to sepsis from osteomyelitis of a comminuted midfacial fracture. These cases demonstrate two unusual and occult conditions that may be present in recently retrieved juvenile fur seals. Failure to establish the correct diagnosis rapidly may result in death soon after capture. The usefulness of imaging techniques such as CT scanning in delineating underlying injuries prior to necropsy is clearly demonstrated.     

Decompensated cirrhosis-related admissions in a large urban hospital in Uganda: prevalence,clinical and laboratory features and implications for planning patient management

Background

Cirrhosis-related complications are a major cause of morbidity and mortality in areas where its risk factors are endemic.

Objective

We determined the prevalence of decompensated cirrhosis among patients on the gastroenterology service of Mulago Hospital and described the clinical and laboratory features of these patients.

Methods

All patients admitted to the unit were assessed and their diagnosis documented. Patients with cirrhosis had clinical features of decompensation recorded. History of alcohol consumption was taken and testing for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) performed.

Results

Between September 2010 and January 2011, we enrolled 482 patients. The majority (53.7%) were male, overall median age 38 years. Decompensated cirrhosis was diagnosed in 85 (17.6%) patients. Of the 85 patients, 47 (55.3%) gave a history of alcohol intake, HBsAg was positive in 23 (27.1%) and anti-HCV in 3 (3.5%). Decompensation was defined by ascites among 81 (95.3%) patients, variceal bleeding in 31 (36.5%), encephalopathy in 20 (23.5%).

Conclusion

Cirrhosis is common in Mulago hospital presenting mainly with ascites and variceal bleeding. Aside from controlling causes of liver diseases, especially alcohol and hepatitis B virus infection, in the interim it is necessary to manage complications in patients who already have cirrhosis.     

Altered mitochondrial metabolism in the insulin‐resistant heart

Obesity‐induced insulin resistance and type 2 diabetes mellitus can ultimately result in various complications, including diabetic cardiomyopathy. In this case, cardiac dysfunction is characterized by metabolic disturbances such as impaired glucose oxidation and an increased reliance on fatty acid (FA) oxidation. Mitochondrial dysfunction has often been associated with the altered metabolic function in the diabetic heart, and may result from FA‐induced lipotoxicity and uncoupling of oxidative phosphorylation. In this review, we address the metabolic changes in the diabetic heart, focusing on the loss of metabolic flexibility and cardiac mitochondrial function. We consider the alterations observed in mitochondrial substrate utilization, bioenergetics and dynamics, and highlight new areas of research which may improve our understanding of the cause and effect of cardiac mitochondrial dysfunction in diabetes. Finally, we explore how lifestyle (nutrition and exercise) and pharmacological interventions can prevent and treat metabolic and mitochondrial dysfunction in diabetes.