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Fulltext AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking

Setta-Kaffetzi N, Simpson MA, Navarini AA, Patel VM, Lu HC, Allen MH, et al.

Am J Hum Genet, 2014 May 01;94(5):790-7.
PMID: 24791904 DOI: 10.1016/j.ajhg.2014.04.005

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis.
Fulltext Activating CARD14 Mutations Are Associated with Generalized Pustular Psoriasis but Rarely Account for Familial Recurrence in Psoriasis Vulgaris

Berki DM, Liu L, Choon SE, David Burden A, Griffiths CEM, Navarini AA, et al.

J Invest Dermatol, 2015 Dec;135(12):2964-2970.
PMID: 26203641 DOI: 10.1038/jid.2015.288

Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Gain-of-function CARD14 mutations have been documented in familial forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent investigations have also implicated CARD14 in the pathogenesis of pustular psoriasis. Follow-up studies, however, have been limited, so that it is not clear to what extent CARD14 alleles account for the above conditions. Here, we sought to address this question by carrying out a systematic CARD14 analysis in an extended patient cohort (n=416). We observed no disease alleles in subjects with familial PV (n=159), erythrodermic psoriasis (n=23), acral pustular psoriasis (n=100), or sporadic PRP (n=29). Conversely, our analysis of 105 individuals with generalized pustular psoriasis (GPP) identified a low-frequency variant (p.Asp176His) that causes constitutive CARD14 oligomerization and shows a significant association with GPP in Asian populations (P=8.4×10(-5); odds ratio=6.4). These data indicate that the analysis of CARD14 mutations could help stratify pustular psoriasis cohorts but would be mostly uninformative in the context of psoriasis and sporadic PRP.
An ionic liquid process for mercury removal from natural gas

Abai M, Atkins MP, Hassan A, Holbrey JD, Kuah Y, Nockemann P, et al.

Dalton Trans, 2015 May 14;44(18):8617-24.
PMID: 25722100 DOI: 10.1039/c4dt03273j

Efficient scrubbing of mercury vapour from natural gas streams has been demonstrated both in the laboratory and on an industrial scale, using chlorocuprate(II) ionic liquids impregnated on high surface area porous solid supports, resulting in the effective removal of mercury vapour from natural gas streams. This material has been commercialised for use within the petroleum gas production industry, and has currently been running continuously for three years on a natural gas plant in Malaysia. Here we report on the chemistry underlying this process, and demonstrate the transfer of this technology from gram to ton scale.
Fulltext Asthma control and asthma treatment adherence in primary care: results from the prospective, multicentre, non-interventional, observational cohort ASCOPE study in Malaysia

Mohd Isa NA, Cheng CL, Nasir NH, Naidu V, Gopal VR, Alexander AK

Med J Malaysia, 2020 07;75(4):331-337.
PMID: 32723990

INTRODUCTION: As the first point of contact for those presenting with asthma symptoms, primary healthcare plays a crucial role in asthma management. This is a nationwide study of assessment of asthma symptom control and adherence to asthma medication among outpatients in public health clinics in Malaysia.

METHODS: This is a prospective, observational multicentre study (ASCOPE; NCT03804632). Data on asthma control, assessment of control symptoms, and adherence to treatment were collected from medical records and interviews of patients. The level of asthma control was assessed using the Global Initiative for Asthma (GINA) Assessment of Symptom Control. Adherence of patient to medication for asthma was assessed through interview of patients using four questions adapted from the Malaysian Medication Adherence Scale.

RESULTS: Among the 1011 patients recruited, 416 (41%) had well controlled asthma, 388 (38%) were partly controlled, and 207 (21%) had uncontrolled asthma. Majority (81%) had mild asthma and all patients were on asthma medication. Most patients did not have spirometry data (97%) but underwent peak flow rate measurements (98%). Poor adherence occurred at all levels of asthma control but was worst among those with uncontrolled asthma. This was statistically significant across all four questions on adherence (p<0.05). For example, more patients with uncontrolled asthma forgot doses (56%) or stopped treatment (39%) than those with well-controlled asthma (44% and 27%respectively).

CONCLUSIONS: Among Malaysian primary care patients with asthma, less than 50% had well-controlled asthma, and low adherence to treatment was common. More effort is needed to improve asthma control among patients in Malaysia, including those with mild asthma.
Classification of leptospiral isolates from Malaya, Thailand and North Borneo

ALEXANDER AD, WETMORE PW, EVANS LB, JEFFRIES H, GLEISER CA

Am J Trop Med Hyg, 1955 May;4(3):492-506.
PMID: 14376775
Fulltext Clinical Course and Characteristics of Generalized Pustular Psoriasis

Choon SE, Navarini AA, Pinter A

Am J Clin Dermatol, 2022 Jan;23(Suppl 1):21-29.
PMID: 35061227 DOI: 10.1007/s40257-021-00654-z

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterized by episodes of widespread sterile macroscopic pustules, with or without systemic inflammation and/or plaque psoriasis. Multiple GPP subtypes have been described, from acute GPP of von Zumbusch to milder, annular pustular psoriasis. Generalized pustular psoriasis mainly affects adults, with a female preponderance, but juvenile GPP also occurs. Flares are a hallmark of GPP and may occur de novo or be provoked by triggers, including withdrawal of systemic corticosteroids, infections, stress, pregnancy, and menstruation. Severity of flares varies widely between patients, and between flares in an individual patient. Significant flares are often accompanied by systemic symptoms, notably fever, general malaise, and extracutaneous manifestations such as arthritis, uveitis, and neutrophilic cholangitis. Common laboratory abnormalities include neutrophilia, elevated C-reactive protein levels, hypocalcemia, and abnormal liver function tests. The clinical course of GPP is highly variable; it can be a relapsing disease with recurrent flares and no pustulation between flares or a persistent disease with perpetual mild pustulation punctuated with flares of greater severity. Patients may have multiple flares per year or a flare every few years. Most flares last 2-5 weeks and approximately 50% require hospitalization. Life-threatening complications include sepsis and renal, hepatic, respiratory, and heart failure. Reported mortality rates are 2-16%.
Fulltext Clinical Disease Measures in Generalized Pustular Psoriasis

Burden AD, Choon SE, Gottlieb AB, Navarini AA, Warren RB

Am J Clin Dermatol, 2022 Jan;23(Suppl 1):39-50.
PMID: 35061231 DOI: 10.1007/s40257-021-00653-0

Generalized pustular psoriasis (GPP) is a rare neutrophilic skin condition characterized by episodes of widespread eruption of sterile macroscopic pustules that can be associated with systemic inflammation. The rarity of GPP and its heterogeneous cutaneous and extracutaneous symptoms pose considerable challenges to the development and adoption of comprehensive accurate disease measures for the routine clinical assessment of disease severity and the evaluation of new treatments in clinical trials. Psoriasis disease measures remain among the most commonly used methods for evaluating patients with GPP, despite their limitations owing to a lack of assessment of pustules (a hallmark of GPP), systemic inflammation, and disease symptoms. The adaptation of psoriasis disease measures and the development of assessment tools specific for GPP severity will enable more effective and accurate monitoring of patients with GPP and enhance the clinical development of new therapies. Further clinical validation of recently developed modified assessment tools, such as the Generalized Pustular Psoriasis Physician Global Assessment and the Generalized Pustular Psoriasis Area and Severity Index, and international consensus on using quantitative tools and patient-reported outcome measures in the development of new treatments are needed to advance patient care.
Fulltext Clinical and genetic differences between pustular psoriasis subtypes

Twelves S, Mostafa A, Dand N, Burri E, Farkas K, Wilson R, et al.

J Allergy Clin Immunol, 2019 03;143(3):1021-1026.
PMID: 30036598 DOI: 10.1016/j.jaci.2018.06.038

BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations.
OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort.
METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases.
RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P
Fulltext Clinical standards for the diagnosis and management of asthma in low- and middle-income countries

Jayasooriya S, Stolbrink M, Khoo EM, Sunte IT, Awuru JI, Cohen M, et al.

Int J Tuberc Lung Dis, 2023 Sep 01;27(9):658-667.
PMID: 37608484 DOI: 10.5588/ijtld.23.0203

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.
Differential Diagnosis of Flavivirus Infections in Horses Using Viral Envelope Protein Domain III Antigens in Enzyme-Linked Immunosorbent Assay

Piyasena TBH, Setoh YX, Hobson-Peters J, Prow NA, Bielefeldt-Ohmann H, Khromykh AA, et al.

Vector Borne Zoonotic Dis, 2017 12;17(12):825-835.
PMID: 29083957 DOI: 10.1089/vbz.2017.2172

In Australia, infection of horses with the West Nile virus (WNV) or Murray Valley encephalitis virus (MVEV) occasionally results in severe neurological disease that cannot be clinically differentiated. Confirmatory serological tests to detect antibody specific for MVEV or WNV in horses are often hampered by cross-reactive antibodies induced to conserved epitopes on the envelope (E) protein. This study utilized bacterially expressed recombinant antigens derived from domain III of the E protein (rE-DIII) of MVEV and WNV, respectively, to determine whether these subunit antigens provided specific diagnostic markers of infection with these two viruses. When a panel of 130 serum samples, from horses with known flavivirus infection status, was tested in enzyme-linked immunosorbent assay (ELISA) using rE-DIII antigens, a differential diagnosis of MVEV or WNV was achieved for most samples. Time-point samples from horses exposed to flavivirus infection during the 2011 outbreak of equine encephalitis in south-eastern Australia also indicated that the rE-DIII antigens were capable of detecting and differentiating MVEV and WNV infection in convalescent sera with similar sensitivity and specificity to virus neutralization tests and blocking ELISAs. Overall, these results indicate that the rE-DIII is a suitable antigen for use in rapid immunoassays for confirming MVEV and WNV infections in horses in the Australian context and warrant further assessment on sensitive, high-throughput serological platforms such as multiplex immune assays.
Fulltext Fetal Brain Infection Is Not a Unique Characteristic of Brazilian Zika Viruses

Setoh YX, Peng NY, Nakayama E, Amarilla AA, Prow NA, Suhrbier A, et al.

Viruses, 2018 10 03;10(10).
PMID: 30282919 DOI: 10.3390/v10100541

The recent emergence of Zika virus (ZIKV) in Brazil was associated with an increased number of fetal brain infections that resulted in a spectrum of congenital neurological complications known as congenital Zika syndrome (CZS). Herein, we generated de novo from sequence data an early Asian lineage ZIKV isolate (ZIKV-MY; Malaysia, 1966) not associated with microcephaly and compared the in vitro replication kinetics and fetal brain infection in interferon α/β receptor 1 knockout (IFNAR1-/-) dams of this isolate and of a Brazilian isolate (ZIKV-Natal; Natal, 2015) unequivocally associated with microcephaly. The replication efficiencies of ZIKV-MY and ZIKV-Natal in A549 and Vero cells were similar, while ZIKV-MY replicated more efficiently in wild-type (WT) and IFNAR-/- mouse embryonic fibroblasts. Viremias in IFNAR1-/- dams were similar after infection with ZIKV-MY or ZIKV-Natal, and importantly, infection of fetal brains was also not significantly different. Thus, fetal brain infection does not appear to be a unique feature of Brazilian ZIKV isolates.
First description of the tadpole of Theloderma ryabovi Orlov, Dutta, Ghate et Kent, 2006 (Anura: Rhacophoridae), an endemic mossy frog from Vietnam

Kropachev II, Orlov NL, Ostroshabov AA, Nguyen TT

Zootaxa, 2019 Aug 15;4657(1):zootaxa.4657.1.13.
PMID: 31716807 DOI: 10.11646/zootaxa.4657.1.13

To date, 26 species of Theloderma have been described and all are distributed throughout Southeast Asia from Assam in northeastern India to Myanmar, Indochina, the Malay Peninsula, and the islands of the Greater Sundas: Sumatra and Borneo (Frost 2019). The tadpoles of only 12 species have been described and published: T. asperum (Boulenger); T. auratum Poyarkov, Kropachev, Gogoleva Orlov; T. bicolor (Bourret); T. corticale (Boulenger); T. gordoni Taylor; T. horridum (Boulenger); T. leave (Smith); T. moloch (Annandale); T. nebulosum Rowley, Le, Hoang, Dau Cao; T. palliatum Rowley, Le, Hoang, Dau Cao; T. stellatum Taylor; T. vietnamense Poyarkov, Orlov, Moiseeva, Pawangkhanant, Ruangsuwan, Vassilieva, Galoyan, Nguyen Gogoleva (Boulenger 1903; Annandale 1912; Wassersug et al. 1981; Inger et al. 1999; Leong Lim 2003; Inthara et al. 2005; Rowley et al. 2011; Gawor et al. 2012; Orlov et al. 2012; Poyarkov et al. 2015; Kropachev et al. 2018).
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
IL36RN mutations define a severe autoinflammatory phenotype of generalized pustular psoriasis

Hussain S, Berki DM, Choon SE, Burden AD, Allen MH, Arostegui JI, et al.

J Allergy Clin Immunol, 2015 Apr;135(4):1067-1070.e9.
PMID: 25458002 DOI: 10.1016/j.jaci.2014.09.043
International Consensus Definition and Diagnostic Criteria for Generalized Pustular Psoriasis From the International Psoriasis Council

Choon SE, van de Kerkhof P, Gudjonsson JE, de la Cruz C, Barker J, Morita A, et al.

JAMA Dermatol, 2024 May 01.
PMID: 38691347 DOI: 10.1001/jamadermatol.2024.0915

IMPORTANCE: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons.
OBJECTIVE: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method.
EVIDENCE REVIEW: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion.
FINDINGS: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques."
CONCLUSIONS AND RELEVANCE: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.
Fulltext Isolation, Identification, Whole-Genome Sequencing, and Annotation of Four Bacillus Species, B. anthracis RIT375, B. circulans RIT379, B. altitudinis RIT380, and B. megaterium RIT381, from Internal Stem Tissue of the Insulin Plant Costus igneus

Polter SJ, Caraballo AA, Lee YP, Eng WW, Gan HM, Wheatley MS, et al.

Genome Announc, 2015;3(4).
PMID: 26227604 DOI: 10.1128/genomeA.00847-15

Here, we report the isolation, identification, whole-genome sequencing, and annotation of four Bacillus species from internal stem tissue of the insulin plant Costus igneus, grown in Puerto Rico. The plant is of medicinal importance, as extracts from its leaves have been shown to lower blood sugar levels of hyperglycemic rats.
Leptospirosis in Malaya. II. Antigenic analysis of 110 leptospiral strains and other serologic studies

ALEXANDER AD, EVANS LB, TOUSSAINT AJ, MARCHWICKI RH, McCRUMB FR

Am J Trop Med Hyg, 1957 Sep;6(5):871-89.
PMID: 13470208
Low magnesium diet alters distribution of macroelements and trace elements in tissues and organs of female rats

Zheltova AA, Kharitonova MV, Iezhitsa IN, Serebryansky EP, Evsyukov OY, Spasov AA, et al.

J Trace Elem Med Biol, 2017 Jan;39:36-42.
PMID: 27908421 DOI: 10.1016/j.jtemb.2016.07.002

The aim of the present study was to assess whether dietary magnesium deficiency can alter distribution of macroelements and trace elements in different organs and tissues. Experiments were carried out on 12 adult female Wistar rats, which were fed either a diet with low Mg content (≤20mgkg(-1) of diet) (LMgD) or a diet with daily recommended Mg content (≈500mgkg(-1)) as control group (CG) for 70 days. On the 70th day of the experiment heart, aorta, femoral skeletal muscle, forebrain, cerebellum, pituitary gland, thyroid gland, ovaries, uterus, liver, kidneys, and spleen were taken for analysis of mineral content. Concentrations of Fe and Ca were measured by inductively coupled plasma-atomic emission spectrometry, and levels of Na, K, Mg, Co, Cu, Zn, Ni, Se, I were determined by inductively coupled plasma mass spectrometry. On the 70th day, LMgD led to significant reduction of Mg level in red blood cells, plasma, aorta, uterus and thyroid gland compared to CG as well as resulted in significant decrease of Mg/Ca ratio in kidneys, spleen and ovaries. Contrary to this, an increase of Mg/Ca ratio was found in cerebellum of LMgD group. Significant decrease of K concentration was shown in aorta of LMgD animals compared to CG whereas myocardial K concentration was increased in LMgD group. Na level was two-fold higher in skeletal muscles of rats that received LMgD in comparison to CG (p=0.006). Increased concentrations of Fe in ovaries and uterus were found in LMgD. Mg restriction did not affect Zn concentration in any of tasted tissues. Se level was higher in spleen and lower in uterus of LMgD animals compared to CG. MgD was accompanied by increased level of Co in skeletal muscles and decreased its level in kidneys and uterus. LMgD feeding was associated with decreased concentrations of Ni in heart, thyroid gland, spleen, uterus and Co in heart, aorta, liver, kidneys, spleen and ovaries. The changes of Mg, K, Co content were accompanied by dramatic (10-fold) decrease of I concentration in aorta of LMgD animals. LMgD causes decrease of I content in ovaries and increase of I level in uterus vs CG. Thus, distribution of macroelements (Ca, Na, K) was weakly affected by Mg restriction that led to the most evident alterations of Co and Ni tissue levels. Moreover, mineral balance of uterus seems to be the most susceptible to low Mg intake. Hypomagnesaemia resulted in significant changes of 5 studied trace elements (Fe, Se, Cu, Ni and Co).
Mechanisms of cataractogenesis in the presence of magnesium deficiency

Agarwal R, Iezhitsa IN, Agarwal P, Spasov AA

Magnes Res, 2013 Jan-Feb;26(1):2-8.
PMID: 23708888 DOI: 10.1684/mrh.2013.0336

Senile cataract is the most common cause of bilateral blindness and results from the loss of transparency of the lens. Maintenance of the unique tissue architecture of the lens is vital for keeping the lens transparent. Membrane transport mechanisms utilizing several magnesium (Mg)-dependent ATPases, play an important role in maintaining lens homeostasis. Therefore, in Mg-deficiency states, ATPase dysfunctions lead to intracellular depletion of K(+) and accumulation of Na(+) and Ca(2+). High intracellular Ca(2+) causes activation of the enzyme calpain II, which leads to the denaturation of crystallin, the soluble lens protein required for maintaining the transparency of the lens. Mg deficiency also interferes with ATPase functions by causing cellular ATP depletion. Furthermore, Mg deficiency enhances lenticular oxidative stress by increased production of free radicals and depletion of antioxidant defenses. Therefore, Mg supplementation may be of therapeutic value in preventing the onset and progression of cataracts in conditions associated with Mg deficiency.
Melioidosis in Malaysia. 3. Antibodies to Pseudomonas pseudomallei in the human population

Strauss JM, Alexander AD, Rapmund G, Gan E, Dorsey AE

Am J Trop Med Hyg, 1969 Sep;18(5):703-7.
PMID: 5817889

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