Paediatric poisoning in Kuwait-Al Adan joint hospital: The need for functional poisoning control centre in Kuwait.

Poisoning is a major global health concern. Every year, unintentional poisoning contributes to 106,683 deaths globally. In Kuwait, paediatric poisoning cases comprise approximately 50% of total poisoning cases. Despite the extensive importance and the long history of poison control centres (PCCs) and the emphasis of the World Health Organization (WHO) to establish a PCC in Kuwait, no functional PCC exists in Kuwait. Here we reported 82 poisoning cases between July and December 2020, revealing a 100% increase in comparison to the official figures published in 2004 and 2005. No fatalities were reported, and all cases were discharged home within 12 h of their visit to the casualty. Children aged 2 to < 4 years comprised the most reported poisoning cases with approximately 45% of the total. The number of male child poisoning cases was approximately two-fold of female children. The most common poisoning agent was silica gel granules (9%) followed by medicines - reported as paracetamol (7%), diclofenac (7%), multivitamin gummies (7%) and vitamin C (5%). Among other causes of poisoning were ingestion of salbutamol nebulizer solution (4%), oral contraceptives and insecticides (4%). These findings reveal the importance of establishing a functional PCC in Kuwait to minimise the unnecessary visits following ingestion of expired orange juice and henna, that may encounter further contraction of infections, especially with the current state of the COVID-19 pandemic. Moreover, a functional PCC would provide comprehensive data and hence further intervention such as shifting the dosage form of salbutamol from nebulizer solution to metered dose inhaler with a spacer, in addition to increasing public awareness towards minimizing such a dramatic increase in casualty visits because of -suspected poisoning.

Correcting hypokalaemia in a paediatric patient with Bartter syndrome through oral dose of potassium chloride intravenous solution.

Bartter syndrome is a rare autosomal recessive disorder characterized by hypokalaemia. Hypokalaemia is defined as low serum potassium concentration ˂3.5 mmol/L, which may lead to arrhythmia and death if left untreated. The aim of this case report was to normalize serum potassium concentration without the need for intravenous intervention. A 5-month-old male of 2.7 kg body weight diagnosed with Bartter syndrome was admitted to the general paediatric ward with acute severe hypokalaemia and urinary tract infection. The main challenge was the inability to administer drugs through intravenous route due to compromised body size. Therefore, we shifted the route of administration to the nasogastric tube/oral route. A total of 2 mL of concentrated intravenous potassium chloride (4 mEq potassium) were dissolved in distilled water and administered through nasogastric tube. Serum potassium concentration was rapidly normalized, which culminated in patient discharge. In conclusion, shifting drug administration from intravenous to oral route in a paediatric patient with Bartter syndrome includes numerous advantages such as patient convenience, minimized risk of cannula-induced infection, and reduced nurse workload.

Correcting hypophosphataemia in a paediatric patient with Sanjad-Sakati syndrome through a single oral dose of potassium phosphate intravenous solution.

Sanjad-Sakati syndrome is an autosomal recessive disorder that is quite common in Kuwait. Among a wide range of complications in Sanjad-Sakati syndrome patients is the vulnerability to infections and subsequent hypophosphataemia. Hypophosphataemia is a metabolic alteration that contributes to numerous consequences such as cardiac arrhythmia. Therefore, if hypophosphataemia is left unresolved, it may culminate in death. A 20-month-old boy of 2.5 kg body weight diagnosed with Sanjad-Sakati syndrome was initially admitted to the paediatric intensive care unit after recovering from COVID-19, and then shifted to the general ward. He was diagnosed with recurrent pneumonia and urinary tract infection. After 9 days, the patient showed severe hypophosphataemia with serum phosphate concentration reaching 0.33 mmol/L. Despite the availability of potassium phosphate intravenous solution, it was difficult to administer potassium phosphate intravenously because of the small body size and low body weight of the patient. Therefore, 0.6 mL potassium phosphate containing 2.4 mEq of potassium and 5.3 mEq of phosphate was administered through a nasogastric tube. The patient showed rapid response after a single dose through the nasogastric tube. Such an intervention in Sanjad-Sakati syndrome patients shows possible advantages of shifting drug administration from intravenous to oral route that includes a convenient route of administration, whether in the intensive care unit or in the general ward. Moreover, shifting drug administration from the intravenous to oral route overcomes the risk of cannula-induced infection and reduces nurses' workload.

Dysregulation of TRPV4, eNOS and caveolin-1 contribute to endothelial dysfunction in the streptozotocin rat model of diabetes.

Endothelial dysfunction is a common complication in diabetes in which endothelium-dependent vasorelaxation is impaired. The aim of this study was to examine the involvement of the TRPV4 ion channel in type 1 diabetic endothelial dysfunction and the possible association of endothelial dysfunction with reduced expression of TRPV4, endothelial nitric oxide synthase (eNOS) and caveolin-1. Male Wistar rats (350-450 g) were injected with 65 mg/kg i.p. streptozotocin (STZ) or vehicle. Endothelial function was investigated in aortic rings and mesenteric arteries using organ bath and myograph, respectively. TRPV4 function was studied with fura-2 calcium imaging in endothelial cells cultured from aortas from control and STZ treated rats. TRPV4, caveolin-1 and eNOS expression was investigated in these cells using immunohistochemistry. STZ-treated diabetic rats showed significant endothelial dysfunction characterised by impaired muscarinic-induced vasorelaxation (aortic rings: STZ-diabetics: Emax = 29.6 ± 9.3%; control: Emax = 77.2 ± 2.5% P˂0.001), as well as significant impairment in TRPV4-induced vasorelaxation (aortic rings, 4αPDD STZ-diabetics: Emax = 56.0 ± 5.5%; control: Emax = 81.1 ± 2.1% P˂0.001). Furthermore, STZ-diabetic primary aortic endothelial cells showed a significant reduction in TRPV4-induced intracellular calcium elevation (P˂0.05) compared with the control group. This was associated with significantly lower expression of TRPV4, caveolin-1 and eNOS and this was reversed by insulin treatment of the endothelial cultures from STZ -diabetic rats. Taken together, these data are consistent with the hypothesis that signalling through TRPV4, caveolin-1, and eNOS is downregulated in STZ-diabetic aortic endothelial cells and restored by insulin treatment.

Role of SK channel activation in determining the action potential configuration in freshly isolated human atrial myocytes from the SKArF study.

Inhibition of SK channel function is being pursued in animal models as a possible therapeutic approach to treat atrial fibrillation (AF). However, the pharmacology of SK channels in human atria is unclear. SK channel function is inhibited by both apamin and UCL1684, with the former discriminating between SK channel subtypes. In this proof-of-principle study, the effects of apamin and UCL1684 on right atrial myocytes freshly isolated from patients in sinus rhythm undergoing elective cardiac surgery were investigated. Outward current evoked from voltage clamped human atrial myocytes was reduced by these two inhibitors of SK channel function. In contrast, membrane current underlying the atrial action potential was affected significantly only by UCL1684 and not by apamin. This pharmacology mirrors that observed in mouse atria, suggesting that mammalian atria possess two populations of SK channels, with only one population contributing to the action potential waveform. Immuno-visualization of the subcellular localization of SK2 and SK3 subunits showed a high degree of colocalization, consistent with the formation of heteromeric SK2/SK3 channels. These data reveal that human atrial myocytes express two SK channel subtypes, one exhibiting an unusual pharmacology. These channels contribute to the atrial action potential waveform and might be a target for novel therapeutic approaches to treat supraventricular arrhythmic conditions such as atrial fibrillation.

Dysfunction in nitric oxide synthesis in streptozotocin treated rat aorta and role of methylglyoxal.

Diabetic vascular dysfunction is a major complication of diabetes. Methylglyoxal (MGO) is a dicarbonyl metabolite elevated in diabetic plasma that reacts with interstitial molecules to form advanced glycation end products (AGE). We investigated whether MGO affects the release of nitric oxide (NO) from rat aortic smooth muscle cells (ASMCs), and if L-arginine can prevent these effects of MGO. MGO was significantly elevated in serum from streptozotocin (STZ)-treated rats (121 ±â€¯11.2 µM) compared with vehicle control rats (27.5 ±â€¯9.2 µM). The pathological concentration of MGO (100 µM) was then applied to investigate its effect on inducible nitric oxide synthase (iNOS) expression and NO release on interferon-gamma (IFN-γ) (100 IU/ml) and lipopolysaccharide (LPS) (100 µg/ml)-stimulated control ASMCs. MGO (100 µM) inhibited IFN-γ and LPS-stimulated iNOS expression through inhibiting Akt phosphorylation and inhibition of iNOS expression was prevented by L-arginine (100 µM) co-treatment. These findings show for the first time that MGO inhibits IFN-γ and LPS-stimulated iNOS expression in ASMCs, in addition to inhibiting IFN-γ and LPS-induced Akt phosphorylation. The actions of MGO might contribute to the vascular dysfunction induced by MGO in diabetes.

Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin-1, and endothelial dysfunction in streptozotocin treated rats.

BACKGROUND: Diabetes is a complex progressive disease characterized by chronic hyperglycaemia and dyslipidaemia associated with endothelial dysfunction. Oxidized LDL (Ox-LDL) is elevated in diabetes and may contribute to endothelial dysfunction. The aim of this study was to relate the serum levels of Ox-LDL with endothelial dysfunction in streptozotocin (STZ)-diabetic rats and to further explore the changes in endothelial nitric oxide synthase (eNOS) and caveolin-1 (CAV-1) expression in primary aortic endothelial cells. METHODS: Diabetes was induced with a single intraperitoneal injection of STZ in male Wistar rats. During the hyperglycaemic diabetes state serum lipid markers, aortic relaxation and aortic endothelial cell eNOS and CAV-1 protein expressions were measured. RESULTS: Elevated serum Ox-LDL (STZ 1486 ± 78.1 pg/mL vs control 732.6 ± 160.6 pg/mL, P < .05) was associated with hyperglycaemia (STZ 29 ± 0.9 mmol/L vs control: 7.2 ± 0.2 mmol/L, P < .001) and hypertriglyceridaemia (STZ 9.0 ± 1.5 mmol/L vs control: 3.0 ± 0.3 mmol/L, P < .01) in diabetic rats. A significant reduction was observed in STZ-diabetic aortic endothelial cell eNOS and CAV-1 of 40% and 30%, respectively, accompanied by a compromised STZ-diabetic carbachol-induced vasodilation (STZ 29.6 ± 9.3% vs control 77.2 ± 2.5%, P < .001). CONCLUSIONS: The elevated serum Ox-LDL in hyperglycaemic STZ-diabetic rats may contribute to diabetic endothelial dysfunction, possibly through downregulation of endothelial CAV-1 and eNOS.

Methylglyoxal, A Metabolite Increased in Diabetes is Associated with Insulin Resistance, Vascular Dysfunction and Neuropathies.

BACKGROUND: Diabetes mellitus (DM) is a pandemic metabolic disease characterized by a chronically elevated blood glucose concentration (hyperglycemia) due to insulin dysfunction. Approximately 50% of diabetics show diabetes complications by the time they are diagnosed. Vascular dysfunction, nephropathy and neuropathic pain are common diabetes complications. Chronic hyperglycemia contributes to reactive oxygen species (ROS) generation such as methylglyoxal (MGO). METHODS: Peer reviewed research papers were studied through bibliographic databases searching focused on review questions and inclusion/exclusion criteria. The reviewed papers were appraised according to the searching focus. The characteristics of screened papers were described, and a deductive qualitative content analysis methodology was applied to the included studies using a conceptual framework to yield this comprehensive systematic review. RESULTS: Sixty-six papers were included in this review. Eleven papers related methylglyoxal generation to carbohydrates metabolism, ten papers related lipid metabolism to methylglyoxal and 5 papers showed the proteolytic pathways that contribute to methylglyoxal generation. Methylglyoxal metabolism was derived from 7 papers. Descriptive figure 1 was drawn to explain methylglyoxal sources and how diabetes increases methylglyoxal generation. Furthermore, twenty-six papers related methylglyoxal to diabetes complications from which 9 papers showed methylglyoxal ability to induce insulin dysfunction, an effect which was described in schematic figure 2. Additionally, fifteen papers revealed methylglyoxal contribution to vascular dysfunction and 3 papers showed methylglyoxal to cause neuropathic pain. Methylglyoxal-induced vascular dysfunction was drawn in a comprehensive figure 3. This review correlated methylglyoxal with diabetes and diabetes complications which were summarised in table 1. CONCLUSION: The findings of this review suggesting methylglyoxal as an essential therapeutic target for managing diabetes in the future.