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Occurrence and level of emerging organic contaminant in fish and mollusk from Klang River estuary, Malaysia and assessment on human health risk

Omar TFT, Aris AZ, Yusoff FM, Mustafa S

Environ Pollut, 2019 May;248:763-773.
PMID: 30851586 DOI: 10.1016/j.envpol.2019.02.060

The occurrence, level, and distribution of multiclass emerging organic contaminants (EOCs) in fish and mollusks from the Klang River estuary were examined. The targeted EOCs for this assessment were phenolic endocrine disrupting compounds (bisphenol A, 4-OP, and 4-NP), organophosphorous pesticides (quinalphos, chlorpyrifos, and diazinon), estrogenic hormones (E2, E1, and EE2), and pharmaceutically active chemicals (primidone, sulfamethoxazole, dexamethasone, diclofenac, amoxicillin, progesterone, and testosterone). Results from this study showed that the prevalent contamination of the Klang River estuary by EOCs with diclofenac, bisphenol A, progesterone, and amoxicillin were predominantly detected in fish and mollusks. Among the EOCs, diclofenac and progesterone had the highest concentrations in fish and mollusk samples, respectively. The concentrations of diclofenac and progesterone in fish and mollusk samples range from 1.42 ng/g to 10.76 ng/g and from 0.73 ng/g to 9.57 ng/g, respectively. Bisphenol A should also be highlighted because of its significant presence in both fish and mollusks. The concentration of bisphenol A in both matrices range from 0.92 ng/g to 5.79 ng/g. The calculated hazard quotient (HQ) for diclofenac, bisphenol A, and progesterone without consideration to their degradation byproduct were less than one, thus suggesting that the consumption of fish and mollusks from the Klang River estuary will unlikely pose any health risk to consumers on the basis of the current assessment. Nonetheless, this preliminary result is an important finding for pollution studies in Malaysian tropical coastal ecosystems, particularly for organic micropollutant EOCs, and can serve as a baseline database for future reference.

Matched MeSH terms: Dexamethasone
Fulltext A Synthetic Curcuminoid Analogue, 2,6-Bis-4-(Hydroxyl-3-Methoxybenzylidine)-Cyclohexanone (BHMC) Ameliorates Acute Airway Inflammation of Allergic Asthma in Ovalbumin-Sensitized Mice

Tham CL, Yeoh SY, Ong CH, Harith HH, Israf DA

Mediators Inflamm, 2021;2021:9725903.
PMID: 33883974 DOI: 10.1155/2021/9725903

2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA-challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.

Matched MeSH terms: Dexamethasone
Fulltext Primary plasma cell leukaemia in a 39-year-old man

Kasinathan G

BMJ Case Rep, 2020 Jul 23;13(7).
PMID: 32709663 DOI: 10.1136/bcr-2020-235543

Plasma cell leukaemia (PCL) is an aggressive haematological malignancy which is classified into primary (pPCL) and secondary PCL. A 39-year-old Indian man presented to the Department of Hematology with a 2-week history of fever and lethargy. Clinically, he was pale and febrile. Haemogram revealed bicytopenia with leucocytosis. The peripheral blood film portrayed rouleax formation with 45% of circulating plasma cells. Serum protein electrophoresis and immunofixation revealed IgG lambda paraproteinaemia of 48 g/L. Bone marrow aspirate, flow cytometry and trephine were consistent with IgG lambda pPCL. He was treated with six cycles of bortezomib, thalidomide and dexamethasone combination chemotherapy followed by high-dose melphalan conditioning and autologous stem cell transplant. Currently, he is in complete remission for the past 18 months and is on oral lenalidomide maintenance therapy. Prognosis is often dismal in pPCL with the median overall survival below 1 year if treatment is delayed.

Matched MeSH terms: Dexamethasone
Fulltext Corneal laceration caused by river crab

Vinuthinee N, Azreen-Redzal A, Juanarita J, Zunaina E

Clin Ophthalmol, 2015;9:203-6.
PMID: 25678769 DOI: 10.2147/OPTH.S74548

A 5-year-old boy presented with right eye pain associated with tearing and photophobia of 1-day duration. He gave a history of playing with a river crab when suddenly the crab clamped his fingers. He attempted to fling the crab off, but the crab flew and hit his right eye. Ocular examination revealed a right eye corneal ulcer with clumps of fibrin located beneath the corneal ulcer and 1.6 mm level of hypopyon. At presentation, the Seidel test was negative, with a deep anterior chamber. Culture from the corneal scrapping specimen grew Citrobacter diversus and Proteus vulgaris, and the boy was treated with topical gentamicin and ceftazidime eyedrops. Fibrin clumps beneath the corneal ulcer subsequently dislodged, and revealed a full-thickness corneal laceration wound with a positive Seidel test and shallow anterior chamber. The patient underwent emergency corneal toileting and suturing. Postoperatively, he was treated with oral ciprofloxacin 250 mg 12-hourly for 1 week, topical gentamicin, ceftazidime, and dexamethasone eyedrops for 4 weeks. Right eye vision improved to 6/9 and 6/6 with pinhole at the 2-week follow-up following corneal suture removal.

Matched MeSH terms: Dexamethasone
Fulltext Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

Lim WL, Idris MM, Kevin FS, Soga T, Parhar IS

Front Endocrinol (Lausanne), 2016;7:117.
PMID: 27630615 DOI: 10.3389/fendo.2016.00117

Maternal dexamethasone [(DEX); a glucocorticoid receptor agonist] exposure delays pubertal onset and alters reproductive behavior in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring's reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1 mg/kg) or vehicle (VEH, water) daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the postsynaptic marker molecule, postsynaptic density 95, was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

Matched MeSH terms: Dexamethasone
Prevention of respiratory distress syndrome

Yu, Victor Y.H.

Malaysian Journal of Child Health, 1993;5(1):3-8.
MyJurnal

ANTENATAL CORTICOSTEROID THERAPY. Benefits. In 1969, the first study was published which showed that prematurely delivered lambs exposed prenatally to corticosteroids survived longer than placebo-treated control animals.' A randomised clinical trial (RCT) followed which demonstrated that antenatal corticosteroid therapy significantly reduced the incidence of respiratory distress syndrome (RDS) in infants born before 2 weeks gestation and reduced mortality in those born before 37 weeks.2 A meta-analysis has been published on 12 RCTs involving over 3000 women in preterm labour, using primarily 24mg of betamethasone or dexamethasone given in 2-6 divided doses over a 48-hour period.' It showed that antenatal corticosteroid therapy is associated with a significant reduction in the risk of RDS (a) if the infant is born > 24 hours or < 7 days of the treatment, (b) in both male and female infants and (c) even in infants < 31 weeks gestation. It also significantly reduces mortality rate and morbidity such as intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC), shortens the duration of hospitalisation and reduces treatment costs. The improvement in survival rate in infants born

Matched MeSH terms: Dexamethasone
Fulltext Diagnostic approach to a functional adrenal tumour in a Shih-Tzu Poodle mix

Tan, L.P., Thong, H.F., Lim, S.Y.

Jurnal Veterinar Malaysia, 2016;28(2):21-23.
MyJurnal

Hyperadrenocorticism is the excessive production of cortisol by the adrenal cortex. 15-20% of hyperadrenocorticism in dogs may be due to functional adrenal tumour. Here we present a case of functional adrenal tumour in a 10 years old Shih-Tzu Poodle mixed-breed dog that was presented to University Veterinary Hospital, Universiti Putra Malaysia. Physical examination findings include multiple cutaneous myiasis, a pendulous abdomen with comedones on the ventral thoracic region and thinning of the skin. Clinical signs shown were polyuria, polydipsia and polyphagia. Serum biochemistry result showed elevated alkaline phosphatase enzyme of 5 folds. Urinary specific gravity was minimally concentrated (1.015). Radiography showed generalised hepatomegaly. Meanwhile, ultrasonography showed unilateral enlargement of the right adrenal gland with mineralisation. Invasion of the right adrenal gland into the caudal vena cava was observed. A differentiation test (high-dose dexamethasone suppression test) was performed and a lack of suppression of the cortisol level was observed. Based on the appropriate clinical signs and physical examination findings, elevated alkaline phosphatase enzyme, minimally concentrated urinary specific gravity, generalised hepatomegaly, unilateral adrenal gland enlargement, and high-dose dexamethasone suppression test, a diagnosis of functional adrenal tumour was made.

Matched MeSH terms: Dexamethasone
Fulltext Atypical contact lens related corneal ulcer caused by pasteurella multocida

Fatin Hanisah, F., Umi Kalthum, M. N., Rona Asnida, N., Jemaima, C. H.

Journal of Surgical Academia, 2018;8(1):43-46.
MyJurnal

A 55-year-old healthy lady with history of regular contact lens (CL) use presented with 10 days history of
progressive left eye blurring of vision, redness and pain. There was good CL hygiene practiced with no history of
swimming, trauma or contact with domestic pets. Left eye vision was hand movement and right eye was 1/60,
pinhole 6/18. On the left eye, there was a central, oval-shaped corneal infiltrate with an overlying large epithelial
defect and stromal oedema, with significant anterior chamber cells and fibrin. B-mode ultrasound showed no vitritis.
Intensive topical benzylpenicillin 10000iu/ml and topical gentamycin 1.4% hourly, homatropine 2% three times
daily, oral doxycycline and oral ascorbic acid were started. The gram stain results showed gram positive cocci
growth. Her ulcer improved with the treatment and preservative-free dexamethasone 0.1% once daily was
commenced to reduce inflammation and scarring. Interestingly, culture was reported as Pasteurella maltocida, a
gram negative bacilli sensitive to penicillin, and so treatment was continued until the ulcer completely healed. She
had central corneal scarring with best corrected vision of 6/24 in the left eye but was not keen on further surgery to
improve her vision. Although it has not been previously reported, Pasteurella multocida can cause CL related
corneal ulcer with severe anterior chamber inflammation. This diagnosis should be considered even if there is trivial
contact or no history of exposure to domestic animals.

Matched MeSH terms: Dexamethasone
Fulltext Co-Occurrence of Exogenous and Endogenous Cushing's Syndromes-Dilemma in Diagnosis

Tong CV, Rajoo S

Case Rep Endocrinol, 2019;2019:2986312.
PMID: 31737375 DOI: 10.1155/2019/2986312

Approach to patients who manifest with features of Cushing's syndrome often begin with exclusion of exposure to excessive exogenous source of glucocorticoids (GC). Most guidelines advocate no further assessment if excessive exogenous GC use is present. We present a case of a 66-year-old lady who was noted to have typical features of Cushing's syndrome. As she gave a very clear history of ingesting exogenous GC for a year, no further work up was undertaken. Despite cessation of GC for a year, she continued to have thin skin and easy bruising. Upon admission for hypertensive emergency, her clinician took note of her changes and investigated her for endogenous Cushing's syndrome. Her cortisol post overnight dexamethasone suppression test was 707 nmol/l. Post low dose dexamethasone suppression test yielded a cortisol of 1133.2 nmol/l. 24 hours urine cortisol was 432.2 nmol/l. Plasma ACTH was 1.1 pmol/l, indicating an ACTH independent Cushing's syndrome. We proceeded with Computed tomography scan (CT scan) of adrenals which revealed a right adrenal adenoma measuring 4.4 × 3.4 × 4.0 cm. Right retroperiteneoscopic adrenalectomy was done. Histopathology examination was consistent with adrenal cortical adenoma with foci of myelolipoma. Post adrenalectomy she developed hypocortisolism secondary to contralateral adrenal suppression which lasted up to the present date. Her cutaneous and musculoskeletal manifestations improved substantially. Co-occurrence of endogenous and exogenous Cushing's syndromes is uncommon but should be considered in patients whose Cushingnoid features do not resolve after cessation of exogenous GC.

Matched MeSH terms: Dexamethasone
Severe Dengue with Hemophagocytosis Syndrome

Ishak SH, Yaacob LH, Ishak A

Malays Fam Physician, 2020;15(1):47-49.
PMID: 32284805

Dengue is known to cause high morbidity and mortality worldwide. In recent years, there have been increasing cases of dengue fever associated with a rare complication: hemophagocytic syndrome (HPS), which is a dangerous disorder that carries high mortality. It is associated with infections, autoimmune disorders, and malignancies. Prolonged duration of fever and cytopenia together with multi-organ dysfunction out of proportion to the plasma leakage phase should alert clinicians to consider this condition. In this case study, we highlight a 45-year-old woman with underlying diabetes who was admitted due to dengue fever with warning signs. Her conditions deteriorated quickly: she had spontaneous bleeding, evidence of plasma leakage, severe hepatitis, and coagulopathy on the 11th day of illness. With the support of other blood results, such as raised serum ferritin and lactate dehydrogenase, she was diagnosed with severe dengue with hemophagocytosis syndrome. She responded well to intravenous dexamethasone and recovered on the 19th day of illness.

Matched MeSH terms: Dexamethasone
Effects of antiemetic doses of dexamethasone on plasma mediators of inflammation resolution and pain after surgery in women

Barden A, Phillips M, Mas E, Hill LM, Mowat I, Loh PS, et al.

Prostaglandins Other Lipid Mediat, 2020 08;149:106427.
PMID: 32084530 DOI: 10.1016/j.prostaglandins.2020.106427

BACKGROUND: Dexamethasone is commonly given as an antiemetic during surgical procedures. It has immunosuppressive effects and can affect key enzymes involved in the synthesis of specialised lipid mediators of inflammation resolution (SPM) that direct inflammation resolution and have anti-nociceptive actions. This study examined the effect of dexamethasone on plasma SPM, and the relationship between SPM and perceived pain in women undergoing surgery.
METHODS: Plasma SPM were measured in samples obtained from two double-blind controlled interventions. The first, included 51 women mean age 53 ± 1.5 years, undergoing breast surgery allocated to either intravenous saline, or dexamethasone (4 mg or 8 mg) after induction of anaesthesia. The second study included 31 women of mean age 44 ± 0.5 years undergoing laparoscopic gynecological surgery that were allocated to either saline, or dexamethasone (4 mg). SPM (18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2) were measured in plasma collected prior to induction of anaesthesia and at 24 h, and 6 weeks post-surgery. Pain was assessed using a verbal analogue scale at discharge from the post-anaesthesia recovery unit. The data from each study was combined to examine the effect of dexamethasone on plasma SPM. The relationship between pain score and SPM was examined using ordinal logistic regression.
RESULTS: The SPM 18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2 were detectable in all plasma samples. There was no significant difference in any SPM due to dexamethasone over the duration of the study. There was a fall in 17-HDHA between baseline and 24 h in both the dexamethasone and saline groups (P = 0.003) but no change in the downstream SPM (RvD1, 17R-RvD1 and RvD2) or 18-HEPE and RvE2. Pain score was negatively related to levels of RvE2 measured prior to induction of anaesthesia (rho = -0.2991, P = 0.006) and positively related to BMI (rho = 0.279, P = 0.011). In ordinal logistic regression the odds ratio for RvE2 was 0.931 (CI 0.880, 0.986; P = 0.014); after adjusting for the effect of BMI indicating that an increase in RvE2 of 1 pg/ml would result in a 6.9 % fall in pain score. Allocation to a dexamethasone group did not influence the pain score or the relationship between RvE2 and pain score.
CONCLUSION: Dexamethasone administered as an anti-emetic does not affect plasma SPM levels. An elevated RvE2 level prior to surgery is predictive of a lower perceived pain score post-anaesthesia.

Matched MeSH terms: Dexamethasone
Fulltext Clinical applications of salivary cortisol measurements

Lo MS, Ng ML, Azmy BS, Khalid BA

Singapore Med J, 1992 Apr;33(2):170-3.
PMID: 1621122

The clinical applications of salivary cortisol measurements were evaluated by radioimmunoassay of time-matched saliva and plasma samples. Salivary cortisol levels of normal subjects exhibited a significant (p less than 0.001) diurnal variation with a mean (+/- SD) concentration of 8.7 +/- 4.8 nmol/L at 0800-1000 h and 2.4 +/- 1.1 nmol/l at 1500-1700 h. After an overnight dexamethasone suppression test, morning salivary cortisol levels decrease to 2.7 +/- 0.7 nmol/L (p less than 0.001 vs normal). An excellent correlation (r = 0.805) of cortisol measurements with time-matched saliva and plasma samples was obtained (y = 0.03x + 0.88, p less than 0.001, n = 91). Hypercortisolism was confirmed by raised salivary cortisols in only half of patients with elevated total plasma levels, thereby indicating that salivary cortisol measurements is a better index of adrenal status.

Matched MeSH terms: Dexamethasone
Fulltext Intranasal administration of Lignosus rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) extract attenuates airway inflammation in murine model of allergic asthma

Muhamad SA, Muhammad NS, Ismail NDA, Mohamud R, Safuan S, Nurul AA

Exp Ther Med, 2019 May;17(5):3867-3876.
PMID: 30988772 DOI: 10.3892/etm.2019.7416

Asthma is a chronic inflammatory disorder in the airways that involves the activation of cells and mediators. Lignosus rhinocerotis (Cooke) Ryvardan or Tiger Milk mushroom is a medicinal mushroom that is traditionally used to treat inflammatory diseases including asthma. In this study, the protective effects of intranasal administration of L. rhinocerotis extract (LRE) in ovalbumin (OVA)-induced airway inflammation mouse model were investigated. Mice were sensitized by intraperitoneal (i.p) injection on days 0 and 14, followed by a daily challenge with 1% OVA from days 21 to 27. Following OVA challenge, LRE and dexamethasone were administered via intranasal and i.p. injection respectively. On day 28, the level of serum immunoglobulin (Ig)E, differential cell counts and T-helper (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) fluid, cell subset population in lung-draining lymph nodes (LNs), leukocytes infiltration and mucus production in the lungs of the animals was measured. Results demonstrated that intranasal administration of LRE significantly suppressed the level of inflammatory cell counts in BALF as well as populations of CD4+ T-cells in lung draining LNs. Apart from that, LRE also significantly reduced the level of Th2 cytokines in BALF and IgE in the serum in OVA-induced asthma. Histological analysis also demonstrated the amelioration of leukocytes infiltration and mucus production in the lungs. Overall, these findings demonstrated the attenuation of airway inflammation in the LRE-treated mice therefore suggesting a promising alternative for the management of allergic airway inflammation.

Matched MeSH terms: Dexamethasone
Fulltext Treatment Pattern and Outcome of Newly Diagnosed Multiple Myeloma Patients in a Resource-Limited Setting

Cheong CS, Tengku K Aziz TAH, Anuar NA, Bee PC, Chin EFM, Khairullah S, et al.

Asian Pac J Cancer Prev, 2024 Feb 01;25(2):595-601.
PMID: 38415546 DOI: 10.31557/APJCP.2024.25.2.595

BACKGROUND: Multiple myeloma is the third most common hematologic malignancy in Malaysia. The introduction of novel agents over the past decades has improved patient outcome and survival substantially. However, these agents incur significant economic burden, thus leading to limited use in less developed countries. This study aims to report on the real-world treatment pattern and outcome of newly diagnosed multiple myeloma (NDMM) patients from a resource-constraint setting.
METHODS: This is a retrospective study on NDMM patients diagnosed between 1 January 2008 and 31 December 2022 in a single academic center. Patients' demographic and treatment details were included for analysis of progression free survival (PFS) and overall survival (OS).
RESULTS: One hundred and thirty-six NDMM patients with a median age of 64.0 years (ranged from 38 to 87 years old) were included. Bortezomib-containing regimens were the most commonly used induction agent, followed by thalidomide. Almost half of the patients (47.1%) achieved very good partial response (VGPR) or complete remission (CR), while 31.6% achieved partial response (PR). Bortezomib containing regimen was associated with significantly deeper and more rapid response, (p=0.001 and p=0.017, respectively) when compared to other agents. Only 22.8% of these patients proceeded to upfront autologous haematopoietic stem cell transplantation. The median OS and PFS were 60.0 months and 25.0 months, respectively. Best initial response and upfront autologous stem cell transplantation (ASCT) were significantly associated with better PFS.
CONCLUSION: Achieving at least a VGPR significantly associated with better outcome in NDMM patients. In a resource constrain country, we recommend incorporating bortezomib in the induction therapy followed with an upfront ASCT.

Matched MeSH terms: Dexamethasone
Fulltext Rare Clinical Presentation of Tuberculous Meningitis: A Case Report

Tan JL, Nordin S, Besari AM

Malays J Med Sci, 2017 Oct;24(5):119-123.
PMID: 29386980 MyJurnal DOI: 10.21315/mjms2017.24.5.14

Introduction: Tuberculosis is the second leading cause of death under the category of infectious diseases, after the human immunodeficiency virus (HIV). Tuberculous meningitis (TBM) constitutes about 5% of all extrapulmonary disease worldwide. This report describes a case of Tuberculous meningitis with rare presentation in a 28-year-old woman, who was treated based on a collection of her social background, clinical findings and Multiplex PCR of tuberculosis.
Case presentation: A 28-year-old Malay woman with no significant medical history presented to HUSM with one month history of on and off fever, two weeks history of generalised limbs weakness and one week history of dysphagia. She was reported to have experienced visual hallucination and significant weight loss. Her laboratory result is significant for leukocytosis, elevated ESR and hypernatremia. Non-enhanced and contrast CT scan of the brain showed severe bilateral frontal cerebral atrophy. Cerebral spinal fluid (CSF) for multiplex PCR for Mycobacterium tuberculosis complex was positive. She was promptly started on anti-TB regime combined with dexamethasone. Subsequent follow-up showed significant improvement.
Conclusion: This is a rare clinical manifestation of Tuberculous meningitis that demonstrates the importance of recognising and initiating the treatment early to reduce disabilities and improve clinical outcome.

Matched MeSH terms: Dexamethasone
Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs

Razali N, Agarwal R, Agarwal P, Kapitonova MY, Kannan Kutty M, Smirnov A, et al.

Eur J Pharmacol, 2015 Feb 15;749:73-80.
PMID: 25481859 DOI: 10.1016/j.ejphar.2014.11.029

Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.

Matched MeSH terms: Dexamethasone/adverse effects*
Fulltext The phosphorylation of endogenous Nedd4-2 In Na(+)-absorbing human airway epithelial cells

Ismail NA, Baines DL, Wilson SM

Eur J Pharmacol, 2014 Jun 05;732:32-42.
PMID: 24657276 DOI: 10.1016/j.ejphar.2014.03.005

Neural precursor cell expressed, developmentally down-regulated protein 4-2 (Nedd4-2) mediates the internalisation / degradation of epithelial Na(+) channel subunits (α-, β- and γ-ENaC). Serum / glucocorticoid inducible kinase 1 (SGK1) and protein kinase A (PKA) both appear to inhibit this process by phosphorylating Nedd4-2-Ser(221), -Ser(327) and -Thr(246). This Nedd4-2 inactivation process is thought to be central to the hormonal control of Na(+) absorption. The present study of H441 human airway epithelial cells therefore explores the effects of SGK1 and / or PKA upon the phosphorylation / abundance of endogenous Nedd4-2; the surface expression of ENaC subunits, and electrogenic Na(+) transport. Effects on Nedd4-2 phosphorylation/abundance and the surface expression of ENaC were monitored by western analysis, whilst Na(+) absorption was quantified electrometrically. Acutely (20min) activating PKA in glucocorticoid-deprived (24h) cells increased the abundance of Ser(221)-phosphorylated, Ser(327)-phosphorylated and total Nedd4-2 without altering the abundance of Thr(246)-phosphorylated Nedd4-2. Activating PKA under these conditions did not cause a co-ordinated increase in the surface abundance of α-, β- and γ-ENaC and had only a very small effect upon electrogenic Na(+) absorption. Activating PKA (20min) in glucocorticoid-treated (0.2µM dexamethasone, 24h) cells, on the other hand, increased the abundance of Ser(221)-, Ser(327)- and Thr(246)-phosphorylated and total Nedd4-2; increased the surface abundance of α-, β- and γ-ENaC and evoked a clear stimulation of Na(+) transport. Chronic glucocorticoid stimulation therefore appears to allow cAMP-dependent control of Na(+) absorption by facilitating the effects of PKA upon the Nedd4-2 and ENaC subunits.

Matched MeSH terms: Dexamethasone/pharmacology
Acute hand ischemia after intra-arterial injection of meprobamate powder

Seak CK, Kooi XJ, Seak CJ

J Emerg Med, 2012 Sep;43(3):468-71.
PMID: 22497894 DOI: 10.1016/j.jemermed.2012.02.014

Meprobamate tablets contain microcrystalline cellulose, a potent embolic agent that has been shown to cause gangrene in animal studies. Microvascular embolization caused by microcrystalline cellulose can contribute to the ischemic process.

Matched MeSH terms: Dexamethasone/therapeutic use
Piper sarmentosum prevents glucocorticoid-induced osteoporotic bone resorption by increasing 11β-hydroxysteroid dehydrogenase type 1 activity

Suhana MR, Farihah HS, Faizah O, Nazrun SA, Norazlina M, Norliza M, et al.

Clin Ter, 2011;162(4):313-8.
PMID: 21912818

Osteoporosis is a proven complication of long-term glucocorticoid therapy. Concern on glucocorticoid induced osteoporosis has increased dramatically in recent years with the widespread use of synthetic glucocorticoids. Glucocorticoid action in bone depends upon the activity of 11βhydroxysteroid dehydrogenase type 1 enzyme (11βHSD1). This enzyme plays an important role in regulating corticosteroids by locally interconverting cortisone into active cortisol. This has been demonstrated in primary cultures of human, mouse or rat osteoblasts. Therefore, inhibition of this enzyme may reduce bone resorption markers. Piper sarmentosum (Ps) is a potent inhibitor of 11βHSD1 in liver and adipose tissue. In this study we determined the effect of Ps on 11βHSD1 activity in bones of glucocorticoid-induced osteoporotic rats.

Matched MeSH terms: Dexamethasone/toxicity
Combined treatment modalities for age related macular degeneration

Das RA, Romano A, Chiosi F, Menzione M, Rinaldi M

Curr Drug Targets, 2011 Feb;12(2):182-9.
PMID: 20887244

BACKGROUND: Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50.
OBJECTIVES: The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD.
DATA SOURCES: Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs).
RESULTS: The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease.
CONCLUSIONS: Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of other pathogenetic pathways. Combination therapy is a logical approach to address mechanisms of disease progression that appear to be self-sustaining once initiated.

Matched MeSH terms: Dexamethasone/therapeutic use

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