Studies on Anti-Inflammatory and General Glucocorticoid Physiology in Skeletal Muscles Affected by Duchenne Muscular Dystrophy: An approach towards Exploration of Steroid-Sparing Agents | Chapter 4 | Current Advances in Chemistry and Biochemistry Vol. 7

 The activation of proinflammatory and metabolic biological pathways in skeletal muscle cells is a hallmark of Duchenne muscular dystrophy (DMD). The dystrophin-associated protein complex, a large transmembrane protein complex that acts as a shock absorber during muscle contraction, a receiver and transducer of cellular signals, and a scaffold for signalling proteins, is destabilised in the absence of dystrophin, a protein that provides a link between the extracellular matrix and the myocyte cytoskeleton. The majority of these pathways are inhibited by synthetic glucocorticoids. Hypertension, arrhythmias, hyperglycemia, osteoporosis, weight gain, growth retardation, skin thinning, cushingoid look, and tissue-specific glucocorticoid resistance are all side effects of glucocorticoids. As a result, reducing the glucocorticoid dosage for DMD patients may be advantageous. When looking for compounds that can accomplish similar pathway stabilisation in DMD, a deeper understanding of the primary cellular pathways that are stabilised following synthetic glucocorticoid administration is required. This review gives a quick rundown of the primary anti-inflammatory pathways as well as the metabolic effects of glucocorticoids in DMD-affected skeletal muscle. The known medicines that can stabilise these pathways and could be used as steroid-sparing medicines in combination with glucocorticoid therapy are outlined. This could open up new avenues for research in DMD animal models and/or human trials, potentially resulting in lower glucocorticoid dose regimens for DMD patients.

Author (s) Details

Sandrine Herbelet
Department of Head and Skin, Division of Neurology, Ghent University and Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.

Arthur Rodenbach
Department of Head and Skin, Division of Neurology, Ghent University and Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.

Boel De Paepe
Department of Head and Skin, Division of Neurology, Ghent University and Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium and Neuromuscular Reference Center, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.

Jan L. De Bleecker
Department of Head and Skin, Division of Neurology, Ghent University and Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium and Neuromuscular Reference Center, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.

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Determination of Telmisartan and Hydrochlorothiazide Using HPTLC in Human Plasma: Development and Validation of Bioanalytical Method | Chapter 3 | Current Advances in Chemistry and Biochemistry Vol. 7

 A simple, sensitive, quick, and cost-effective thin layer chromatographic technique was used to determine the concentrations of telmisartan and hydrochlorothiazide in human plasma using paracetamol as an internal reference. A combination of hydrochlorothiazide (HCT) and telmisartan (TEL) is more successful than either medicine alone in the treatment of hypertension.

The plasma sample was collected using a methanol-acetonitrile (3.0:0.1, v/v) mixture. Concentrations of 200, 400, 600, 800, 1000, and 1200 ng/spot were employed for the hydrochlorothiazide and telmisartan calibration curves, respectively. Telmisartan and hydrochlorothiazide, respectively, showed 75.98 percent and 81.91 percent recovery. Chloroform: methanol: toluene (8:2:4 v/v/v) makes up the mobile phase. At a wavelength of 278 nm, densitometric analysis was performed. The Rf values for hydrochlorothiazide, paracetamol, and telmisartan, respectively, were 0.28 0.05, 0.50 0.05, and 0.66 0.05. The stability of telmisartan and hydrochlorothiazide in plasma was validated in three freeze-thaw cycles (20 C), on bench for 24 hours, and post preparative for 48 hours. A recovery study was used to statistically validate the recommended method for identifying telmisartan and hydrochlorothiazide in human plasma. The method is less expensive and faster than previously disclosed approaches. In the future, we may be able to use this technique for bioequivalence research.

Author (s) Details

Ambadas R. Rote
Department of Pharmaceutical Chemistry, MGV's Pharmacy College, Pune University, Nashik, India.

Poonam R. Sonavane
Department of Pharmaceutical Chemistry, MGV's Pharmacy College, Pune University, Nashik, India.

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