Displaying publications 1 - 20 of 49 in total

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  1. Afroze B, Amjad N, Ibrahim SH, Humayun KN, Yakob Y
    Brain Dev, 2014 Nov;36(10):924-7.
    PMID: 24508408 DOI: 10.1016/j.braindev.2013.12.009
    Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) are established subgroups of mitochondrial encephalomyopathy. m.3243A>G a common point mutation is detected in tRNA in majority of patients with MELAS phenotype whereas m.8344A>G point mutation in tRNA is observed, in MERRF phenotype. Adrenal insufficiency has not been reported in mitochondrial disease, except in Kearns-Sayre Syndrome (KSS), which is a mitochondrial deletion syndrome. We report an unusual presentation in a five year old boy who presented with clinical phenotype of MELAS and was found to have m.8344A>G mutation in tRNA. Addison disease was identified due to hyperpigmentation of lips and gums present from early childhood. This is the first report describing adrenal insufficiency in a child with MELAS phenotype.
    Matched MeSH terms: Acidosis, Lactic
  2. Hannah HB
    Br J Anaesth, 1971 Oct;43(10):991-3.
    PMID: 5115036
    Matched MeSH terms: Acidosis
  3. Sharda P, Haspani S, Idris Z
    Asian J Neurosurg, 2014 Oct-Dec;9(4):203-12.
    PMID: 25685217 DOI: 10.4103/1793-5482.146605
    OBJECTIVE: The objective of this prospective cohort study was to analyse the characteristics of severe Traumatic Brain Injury (TBI) in a regional trauma centre Hospital Kuala Lumpur (HKL) along with its impact of various prognostic factors post Decompressive Craniectomy (DC).
    MATERIALS AND METHODS: Duration of the study was of 13 months in HKL. 110 consecutive patients undergoing DC and remained in our centre were recruited. They were then analysed categorically with standard analytical software.
    RESULTS: Age group have highest range between 12-30 category with male preponderance. Common mechanism of injury was motor vehicle accident involving motorcyclist. Univariate analysis showed statistically significant in referral area (P = 0.006). In clinical evaluation statistically significant was the motor score (P = 0.040), pupillary state (P = 0.010), blood pressure stability (P = 0.013) and evidence of Diabetes Insipidus (P < 0.001). In biochemical status the significant statistics included evidence of coagulopathy (P < 0.001), evidence of acidosis (P = 0.003) and evidence of hypoxia (P = 0.030). In Radiological sector, significant univariate analysis proved in location of the subdural clot (P < 0.010), location of the contusion (P = 0.045), site of existence of both type of clots (P = 0.031) and the evidence of edema (P = 0.041). The timing of injury was noted to be significant as well (P = 0.061). In the post operative care was, there were significance in the overall stability in intensive care (P < 0.001), the stability of blood pressure, cerebral perfusion pressure, pulse rates and oxygen saturation (all P < 0.001)seen individually, post operative ICP monitoring in the immediate (P = 0.002), within 24 hours (P < 0.001) and within 24-48 hours (P < 0.001) period, along with post operative pupillary size (P < 0.001) and motor score (P < 0.001). Post operatively, radiologically significant statistics included evidence of midline shift post operatively in the CT scan (P < 0.001). Multivariate logistic regression with stepwise likelihood ratio (LR) method concluded that hypoxia post operatively (P = 0.152), the unmaintained Cerebral Perfusion Pressure (CPP) (P = 0.007) and unstable blood pressure (BP) (P = <0.001). Poor outcome noted 10.2 times higher in post operative hypoxia [OR10.184; 95% CI: 0.424, 244.495]. Odds of having poor outcome if CPP unmaintained was 13.8 times higher [OR: 13.754; CI: 2.050, 92.301]. Highest predictor of poor outcome was the unstable BP, 32 times higher [OR 31.600; CI: 4.530, 220440].
    CONCLUSION: Our series represent both urban and rural population, noted to be the largest series in severe TBI in this region. Severe head injury accounts for significant proportion of neurosurgical admissions, resources with its impact on socio-economic concerns to a growing population like Malaysia. This study concludes that the predictors of outcome in severe TBI post DC were postoperative hypoxia, unmaintained cerebral perfusion pressure and unstable blood pressure as independent predictors of poor outcome. Key words: Decompressive craniectomy, prognostication of decompressive craniectomy, prognostication of severe head injury, prognostication of traumatic brain injury, severe head injury, severe traumatic brain injury, traumatic brain injury.
    KEYWORDS: Decompressive craniectomy; prognostication of decompressive craniectomy; prognostication of severe head injury; prognostication of traumatic brain injury; severe head injury; severe traumatic brain injury; traumatic brain injury
    Matched MeSH terms: Acidosis
  4. Subramaniam G, Achike FI, Mustafa MR
    Regul. Pept., 2009 Jun 5;155(1-3):70-5.
    PMID: 19362578 DOI: 10.1016/j.regpep.2009.04.008
    The effect of acidosis on insulin-induced relaxation was studied in thoracic aortic rings (from Wistar-Kyoto (WKY) rats) with (+ED) or without (-ED) endothelium. The rings were mounted in normal (pH 7.4) or acidotic (pH 7.2) Krebs solution for isometric tension recording. Phenylephrine (PE, 3.0 microM)-contracted tissues were exposed to insulin in the presence or absence of various inhibitors. Insulin exerted similar concentration-dependent relaxation of +ED tissues in normal and acidotic pH. Endothelium denudation, significantly (p<0.05) reduced insulin effect in normal, but not acidotic pH. Under normal pH, treatment with L-NAME or methylene blue significantly (p<0.05) reduced insulin responses in the +ED (but not the -ED) tissues. The insulin effect was also significantly (p<0.05) inhibited by tetraethylammonium (TEA; BK(Ca) blocker), 4-Aminopyridine (4-AP; K(V) channel blocker), combined treatments (L-NAME+4-AP+TEA, in +ED tissues) or (4-AP+TEA, in -ED tissues). In either +ED or -ED tissues, indomethacin (cyclo-oxygenase inhibitor), glibenclamide (K(ATP) channel blocker), barium chloride (K(ir) channel blocker) or Ouabain (a Na(+)/K(+)-ATPase inhibitor) had no effect. Except for methylene blue (effect on +ED tissues), none of the drug treatments inhibited insulin vasodilator effect in acidosis (+ED or -ED tissues). These data indicate that insulin exerts an endothelium-dependent and -independent vasodilatation in rat aorta which in normal pH is mediated via BK(Ca) and K(v) channels, including the EDNO-cGMP cascade. Acidosis abolishes the endothelium-dependent relaxation mechanism unraveling a novel mechanism that is as efficacious and is cGMP-, but not EDNO-, BK(Ca)- or K(v)-mediated.
    Matched MeSH terms: Acidosis/metabolism*
  5. Hashim H, Sahari NS, Sazlly Lim SM, Hoo FK
    Iran Red Crescent Med J, 2015 Oct;17(10):e19546.
    PMID: 26568856 DOI: 10.5812/ircmj.19546
    INTRODUCTION: The introduction of highly active antiretroviral therapy (HAART), in 1996, has resulted in marked reductions in the rate of illness and death, due to HIV infection. The HAART has transformed HIV infection into a manageable chronic disease. However, although many regimens lower plasma viral load, to below the limit of detection, in most patients, maintaining viral load suppression remains challenging, because of adverse effects and toxicity in the long term, which can lead to non-adherence, virologic failure and drug resistance. Although rare, lactic acidosis often develops fatal complications, as reported in several human immunodeficiency virus infected patients treated with nucleoside reverse transcriptase inhibitors (NRTIs). The purpose of this paper is to report a case of tenofovir induced lactic acidosis and review the literature.

    CASE PRESENTATION: A 52-year-old Malay gentleman, with hepatitis C virus and HIV infection was admitted to the intensive care unit for severe lactic acidosis, with concurrent Escherichia coli bacteremia with multiorgan dysfunction. The patient was started on highly active antiretroviral therapy, which included tenofovir, 5 weeks before presentation. Antimicrobial therapy, continuous veno-venous hemofiltration, and other supportive treatments were instituted. However, the patient eventually succumbed to his illness.

    CONCLUSIONS: It is essential for clinicians to be able to recognize the signs and symptoms of lactic acidosis in NRTIs treated HIV patients, as an early diagnosis is important to institute treatment.

    Matched MeSH terms: Acidosis, Lactic
  6. Yeoh C, Teo A, Azhar AMN, Suann ST, Thum Y, Wong KD, et al.
    J Acute Med, 2019 Sep 01;9(3):128-144.
    PMID: 32995241 DOI: 10.6705/j.jacme.201909_9(3).0005
    Background: Balanced fluids are preferred in initial resuscitation of septic patients based on several recent studies. The Stewart's concept on acid-base balance predicts that high strong ion difference (SID) fluid thus will increase the pH level. To date, the impact of high SID fluid in septic patient with metabolic acidosis remains uncertain. We conducted single center, randomized, double-blind trial to compare the effect of high SID fluid vs. Hartmann's solution on acid-base status in selected sepsis patients in the Emergency Department.

    Methods: Septic patient with hyperlactatemia and metabolic acidosis were randomized to receive either high SID fl uid or Hartmann's solution during initial fl uid resuscitation. The primary outcome measures the pH and bicarbonate levels difference pre- and post- resuscitation.

    Results: One hundred and sixty-two patients underwent randomization, 81 were assigned each to receive high SID fluid or Hartmann's solution. Both groups had similar baseline characteristics. High SID group received 23.5 mL/kg and the Hartmann's group received 22.7 mL/kg (p = 0.360). High SID fluid increased the mean (± SD) pH by 0.107 (± 0.09) vs. Hartmann's solution by 0.014 (± 0.12), p ≤ 0.001. Mean bicarbonate level increased signifi cantly in high SID group compared to Hartmann's (4.30 ± 3.76 vs. 1.25 ± 3.33, p ≤ 0.001). High SID group had higher post resuscitation lactate clearance than Hartmann's group (25.4 ± 28.3% vs. 12.0 ± 34.1%, p = 0.009). Shorter hospital stay was observed in highSID group 8.04 ± 5.96 days vs. Hartmann's group 12.18 ± 12.41 days (p = 0.048). Both groups showed no difference in incidence of pulmonary oedema, acute kidney injury and mortality.

    Conclusions: Initial resuscitation using high SID fluid in selected septic patient improves pH and bicarbonate levels. The high SID group had better post resuscitation lactate clearance and shorter hospital stay.

    Matched MeSH terms: Acidosis
  7. Huan, Nai Chien, Wan Awatif Wan Mohd Zohdi
    MyJurnal
    High anion gap metabolic acidosis (HAGMA) is a hallmark of Diabetic Ketoacidosis (DKA). Occasionally, a Normal Anion Gap Metabolic Acidosis (NAGMA) can be seen, especially during the treatment phase. In this case report, a 55-year-old lady with diabetes mellitus who presented with a 2-day history of fever, lethargy and multiple episodes of vomiting and diarrhoea. Initial laboratory investigations revealed: capillary blood glucose as 27 mmol/L, urine ketone as 3+, blood ketone as 3.5 mmol/L, serum bicarbonate as 14 mmol/L, and serum chloride as 95 mmol/L. She was treated with intravenous normal saline fluid resuscitation and constant rate insulin infusion which was fortunately accompanied by stabilization of blood glucose and normalization of blood ketone to 0.2 mmol/L. However, despite normalization of her anion gap (25 to 14), she remained unwell with acidotic breathing due to refractory hyperchloraemic NAGMA with bicarbonate at 11 mol/L and chloride of 112 mmol/L. It was then decided to administer 100 mL of 8.4% Sodium Bicarbonate solution. The next day, she was no longer tachypneic as her bicarbonate and carbon dioxide improved to 21 mmol/L and 32 mmHg respectively. The presence of NAGMA in DKA should prompt clinicians to conduct a thorough search for possible underlying causes, such as gastrointestinal fluid loss, sepsis and chloride load from aggressive fluid resuscitation with normal saline. Sodium bicarbonate should only be considered in intractable cases to correct a NAGMA and not routinely used in the treatment of DKA.
    Matched MeSH terms: Acidosis; Diabetic Ketoacidosis
  8. Usman A, Shaikh MF, Dujaili JA, Mustafa N, Gan SH
    Diabetes Metab Syndr, 2021 Mar 05;15(2):573-580.
    PMID: 33706189 DOI: 10.1016/j.dsx.2021.03.001
    BACKGROUND AND AIMS: Diabetic ketoacidosis (DKA) treatment guidelines recommend to initiate potassium-replacement when serum potassium (SK) drops within normal range, and to withhold insulin if SK is below normal. Despite strict recommendations, hypokalemia is frequently observed in DKA.

    METHODS: Scientific literature was thoroughly searched to find 1) DKA treatment guidelines, 2) studies reporting hypokalemia in DKA, 3) and literature elaborating mechanisms involved in hypokalemia.

    RESULTS: Acidosis affects SK and its regulators including insulin, catecholamines and aldosterone. Current conceptual framework is an argument to gauge the degree of hypokalemia before it strikes DKA patients utilizing SK level after adjusting it with pH. Suggested approach will reduce hypokalemia risk and its associated complications. The nomogram calculates pH-adjusted potassium and expected potassium loss. It also ranks hypokalemia associated risk, and proposes the potassium-replacement rate over given time period. The differences between current DKA treatment guidelines and proposed strategy are also discussed. Moreover, reasons and risk of hyperkalemia due to early initiation of potassium replacement and remedial actions are debated.

    CONCLUSION: In light of proposed strategy, utilizing the nomogram ensures reduced incidence of hypokalemia in DKA resulting in improved clinical and patient outcomes. Pharmacoeconomic benefits can also be expected when avoiding hypokalemia ensures early discharge.

    Matched MeSH terms: Acidosis; Diabetic Ketoacidosis
  9. Firdaus Hayati, Nornazirah Azizan, Nik Amin Sahid, Hilal Zahabi Abdul Fattah, Rohamini Sibin, Andee Dzulkarnaen Zakaria
    MyJurnal
    Necrotizing fasciitis (NF) is a deadly soft tissue infection causing a significant morbidity and mortality. Abdominal and chest wall NF are unusual. We describe a 49-year-old male with anterior abdominal wall NF secondary to per- forated gastric ulcer (PGU). He was admitted in septic shock presenting an abdominal wall NF with severe metabolic acidosis requiring dialysis and admission to the intensive care unit. There was a patch of gangrene with surrounding skin discoloration at lower quadrant of the abdominal wall. Local debridement was done without a preoperative computed tomography that was performed after surgery. Adequate source control was not achieved after the second surgery and the patient had worsened resulting to death. We describe this rare presentation of NF and discuss the issues learnt from this unfortunate event.
    Matched MeSH terms: Acidosis
  10. Wong CK, Md Fuzi NH, Baherin MF, Lee HG
    Med J Malaysia, 2020 03;75(2):171-172.
    PMID: 32281602
    We report a rare case of severe Plasmodium knowlesi malaria and dengue co-infection in a 36-year-old lady with hyperparasitaemia, metabolic acidosis, haemolysis and acute kidney injury. She was in shock requiring inotropic support and elective intubation. She had pericardial tamponade which necessitate pericardiocentesis to allow for haemodynamic stability during haemodialysis. She underwent haemodialysis, was ventilated for six days and stayed in hospital for 29 days. She was discharged home well with almost complete renal recovery. Physicians must have a high degree of suspicion for dengue co-infection in malaria patients with plasma leakage such as pericardial effusion to allow for prompt management.
    Matched MeSH terms: Acidosis
  11. Faridah Hanim Zam Zam, Nazimah Idris, Tham, Seng Woh
    MyJurnal
    Background: Fetal surveillance in labour is performed mostly to identify fetuses at risk of hypoxia in order to reduce neonatal morbidity and mortality by initiating timely intervention. While normal and abnormal fetal heart rate (FHR) patterns have been well recognised and characterized for the first stage of labour, FHR patterns during the second stage of labour commonly showed some forms of abnormalities leading to problems in interpretation, particularly in predicting fetal hypoxia and acidosis. This study aims to identify patterns of FHR tracing during the second stage of labour associated with neonatal acidosis. Methods: A prospective cross sectional study was conducted in the Labour Ward of a state referral hospital. The study population were patients with low-risk
    singleton pregnancies between 37 to 42 weeks gestation who had normal cardiotocograph (CTG) tracing in the first stage of labour. CTG was recorded during the second stage of labour and neonatal umbilical cord blood was obtained for acid-base analysis immediately after birth prior to the delivery of placenta. FHR patterns were grouped according to modified Melchior and Barnard’s
    classification and matched with neonatal acid-base status. Patients with normal FHR pattern in the second stage acted as control. Results: A total of 111 matched pairs were analysed. Ninety nine (89.2%) second stage FHR tracings showed abnormal features when compared to control. There were significantly more neonatal acidosis and hypercapnia in type 1b, type 2a, type 2b and type 3 CTG patterns compared to control, in increasing order of severity. In addition, types 2b and 3 showed significant difference in the base excess. Conclusion: Certain second stage fetal heart rate
    patterns were found to be associated with neonatal acidosis.
    Matched MeSH terms: Acidosis
  12. Low, Qin Jian, Chew, Soo Foong
    MyJurnal
    Both metformin and gliclazide have been used extensively in the management of type II diabetes mellitus. Metformin and gliclazide overdose can lead to severe hypoglycaemia refractory to intravenous (IV) dextrose rescue therapy. A 21-year-old man complained of vomiting and felt dizzy after four hours of taking 70 tablets of Metformin 500 mg and 40 tablets of Gliclazide 80 mg. He had major depressive disorder and wanted to commit suicide. He was given IV Dextrose 50% 50 cc immediately. Octreotide had been used successfully to reverse the refractory hypoglycaemia caused by gliclazide overdose. Unfortunately, he developed severe lactic acidosis with acute kidney injury. Dialysis had been done by continuous venovenous haemodiafiltrationa and intravenous sodium bicarbonate 8.4% infusion was given. However, the patient succumbed due to the severe lactic acidosis and kidney failure despite of urgent dialysis. Octreotide infusion helps in preventing refractory hypoglycaemia secondary to sulfonylurea overdose by inhibit calcium-mediated insulin release. Metformin overdose causes severe lactic acidosis due to conversion of glucose to lactate. Sodium bicarbonate therapy in metformin induced lactic acidosis is also controversial. Though sulfonylurea and metformin are the most commonly-prescribed anti-hypoglycaemic agents, thus during prescribing everyone has to be careful about the overdoses and side effects of these drugs.
    Matched MeSH terms: Acidosis, Lactic
  13. Mazlan MZ, Mohd Zaini RH, Hassan SK, Ali S, Che Omar S, Wan Hassan WMN
    Respir Med Case Rep, 2017;21:129-131.
    PMID: 28487824 DOI: 10.1016/j.rmcr.2017.04.014
    INTRODUCTION: Closed suctioning is commonly used in the context of high-setting mechanical ventilation (MV), given its ability to prevent lung volume loss that otherwise accompanies open suctioning. However, closed suctioning systems (CSS) are not equivalent regarding components and capabilities, and thus this technique may be differentially effective to adequately clear patient secretions from an endotracheal tube (ETT), which is of paramount importance when the tube size makes the ETT particularly vulnerable to block by patient secretions.

    CASE PRESENTATION: A 25-year-old super morbidly obese female (body mass index = 55 kg/meter2) presented with worsening shortness of breath. For MV, pairing of a 6 mm (mm) diameter ETT to accommodate the patient's vocal cord edema, with a CSS not designed to maintain a clean catheter tip, precipitated ETT blockage and respiratory acidosis. Replacement of these devices with a 6.5 mm ETT and a CSS designed to keep the catheter tip clean resolved the complications. After use of the different ETT and CSS for approximately one week, the patient was discharged to home.

    DISCUSSION: The clean-tip catheter CSS enabled a more patent airway than its counterpart device that did not have this feature. Use of a clean-tip catheter CSS was an important care development for this patient, because this individual's super morbidly obese condition minimized tolerance for MV complications that would exacerbate her pre-existing tenuous respiratory health status.

    CONCLUSION: Special attention should be given to the choices of ETT size and CSS to manage super morbidly obese patients who have a history of difficult airway access.

    Matched MeSH terms: Acidosis, Respiratory
  14. Mustafar R, Kamaruzaman L, Chien BH, Yahaya A, Mohd Nasir N, Mohd R, et al.
    Case Rep Med, 2018;2018:8425985.
    PMID: 30186328 DOI: 10.1155/2018/8425985
    We reported a case of primary renal lymphoma (PRL) presented with non-oliguric acute kidney injury and bilateral kidney infiltrates in an individual with human immunodeficiency virus (HIV) disease. Acute kidney injury secondary to lymphoma infiltrates is very rare (less than 1% of hematological malignancy). A 37-year-old gentleman with underlying human immunodeficiency virus (HIV) disease was on combined antiretroviral therapy since diagnosis. He presented to our center with uremic symptoms and gross hematuria. Clinically, bilateral kidneys massively enlarged and were ballotable. Blood investigations showed hemoglobin of 3.7 g/L, urea of 65.6 mmol/L, and serum creatinine of 1630 µmol/L with hyperkalemia and metabolic acidosis. An urgent hemodialysis was initiated, and he was dependent on regular hemodialysis subsequently. Computed tomography renal scan showed diffuse nonenhancing hypodense lesion in both renal parenchyma. Diagnosis of diffuse large B cell lymphoma with germinal center type, CD20 positive, and proliferative index 95% was confirmed via renal biopsy, and there was no bone marrow infiltrates. Unfortunately, the patient succumbs prior to initiation of chemotherapy.
    Matched MeSH terms: Acidosis
  15. Yeo JL, Tan BT, Achike FI
    Eur J Pharmacol, 2010 Sep 10;642(1-3):99-106.
    PMID: 20553918 DOI: 10.1016/j.ejphar.2010.05.040
    Acidosis modulates physiologic and pathophysiologic processes but the mechanism of acidotic vasodilatation remains unclear. We therefore explored this in aortic rings from normal and streptozotocin-induced diabetic Sprague-Dawley rats. Phenylephrine (PE)-induced contraction in endothelium-intact and -denuded rings were recorded under normal and acidotic pH with or without drug probes. Acidosis exerted a relaxant effect in endothelium-intact and -denuded euglycaemic and diabetic tissues. l-NAME or methylene blue partially inhibited acidotic relaxation in these endothelium-intact but not the -denuded tissues, with greater inhibition in the diabetic tissues, indicating that acidosis induces relaxation by endothelium-dependent and -independent mechanisms, the former being EDNO-cGMP mediated. Indomethacin had no effect on the tissues, indicating that cyclooxygenase products are neither involved in acidosis-induced vasodilatation nor in the modulation of phenylephrine-contraction. In euglycaemic tissues under normal pH, no K(+) channel blocker altered phenylephrine-contraction, but all (except glibenclamide) enhanced diabetic tissue contraction, indicating that normally, these channels (K(ir), K(V), BK(Ca), K(ATP)) do not modulate phenylephrine-contraction, but they (except K(ATP)) are expressed in diabetes where they attenuate phenylephine-induced contraction and modulate acidosis. Only the K(ir) channel modulates acidotic relaxation in euglycaemic tissues. Only tetraethylammonium and iberiotoxin enhanced phenylephrine-induced contraction in endothelium-denuded diabetic tissues indicating that BK(Ca) attenuates phenylephrine-contraction and that acidotic relaxation in this condition is modulated by a tetraethylammonium-sensitive mechanism. In conclusion, acidosis causes vasodilatation in normal and diabetic tissues via endothelium-dependent and -independent mechanisms differentially modulated by a combination of a NO-cGMP process and K(+) channels, some of which are dormant in the normal state but activated in diabetes mellitus.
    Matched MeSH terms: Acidosis/physiopathology*
  16. Shmukler BE, Kedar PS, Warang P, Desai M, Madkaikar M, Ghosh K, et al.
    Am J Hematol, 2010 Oct;85(10):824-8.
    PMID: 20799361 DOI: 10.1002/ajh.21836
    Familial distal renal tubular acidosis (dRTA) can be caused by mutations in the Cl2/HCO32 exchanger of the renal Type A intercalated cell, kidney AE1/SLC4A1. dRTA-associated AE1 mutations have been reported in families from North America, Europe, Thailand, Malaysia, Papua-New Guinea, Taiwan, and the Philippines, but not India. The dRTA mutation AE1 A858D has been detected only in the context of compound heterozygosity. We report here two unrelated Indian patients with combined hemolytic anemia and dRTA who share homozygous A858D mutations of the AE1/SLC4A1 gene. The mutation creates a novel restriction site that is validated for diagnostic screening.
    Matched MeSH terms: Acidosis, Renal Tubular/complications; Acidosis, Renal Tubular/genetics*
  17. Campion KL, McCormick WD, Warwicker J, Khayat ME, Atkinson-Dell R, Steward MC, et al.
    J Am Soc Nephrol, 2015 Sep;26(9):2163-71.
    PMID: 25556167 DOI: 10.1681/ASN.2014070653
    The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo.
    Matched MeSH terms: Acidosis/metabolism
  18. Lee WS, Sokol RJ
    J Pediatr, 2013 Oct;163(4):942-8.
    PMID: 23810725 DOI: 10.1016/j.jpeds.2013.05.036
    Matched MeSH terms: Acidosis, Lactic/genetics
  19. Bruce LJ, Wrong O, Toye AM, Young MT, Ogle G, Ismail Z, et al.
    Biochem. J., 2000 Aug 15;350 Pt 1:41-51.
    PMID: 10926824
    We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1) gene associated with distalrenal tubular acidosis (dRTA) in families from Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all three mutations seem to berestricted to South-East Asian populations. South-East Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408, occurred in many of the families but did not itselfresult in dRTA. Compound heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed dominant inheritance and therecessive DeltaV850 and G701D mutations showed a pseudo-dominantphenotype when the transport-inactive SAO allele was also present. Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D mutant proteins have greatly decreased aniontransport when present as compound heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion transport activity so far reported for human red cells. The results suggest dRTA might arise by a different mechanism for eachmutation. We confirm that the G701D mutant protein has an absoluterequirement for glycophorin A for movement to the cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis-targetedto an inappropriate plasma membrane domain in the renal tubular cell,and that the recessive DeltaV850 mutation might give dRTA because ofits decreased anion transport activity.
    Matched MeSH terms: Acidosis, Renal Tubular/genetics*
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