Duration of action of antispasmodic agents: novel use of a mouse model as an in vivo pharmacological assay.

OBJECTIVE: Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm remains a concern. In vitro testing has demonstrated the efficacy of phenoxybenzamine and verapamil/nitroglycerin as topical antispasmodic agents, but their duration of action in vivo is unknown. Using an in vivo mouse model, we measured their duration of action in functioning vascular grafts, and compared this to their in vitro duration of action in ungrafted vascular segments. METHODS: Two millimetre mouse aortic segments (C57/BL6) were incubated with phenoxybenzamine, verapamil/nitroglycerin, or buffer (controls) for 15 min in organ chambers. Isometric tension responses to phenylephrine and prostaglandin F2alpha were measured at 0, 2, 6 and 12 h post-incubation. In parallel, 36 murine infrarenal aortic interposition grafts (2 mm) were performed. Twelve grafts were pre-treated (15 min) with phenoxybenzamine, 12 with verapamil/nitroglycerin and 12 remained untreated (controls). Isometric tension responses to the same agonists were measured in grafts harvested 2, 6, 13 and 23 h after surgery. RESULTS: Phenoxybenzamine prevented alpha-adrenergic vasoconstriction for up to 16 h in vivo (grafts), and 12h in vitro (ungrafted segments). Verapamil/nitroglycerin was effective for at least 2 h in vitro, but did not prevent vasoconstriction after 2 h in vivo. CONCLUSIONS: The mouse model appears to be a useful technique for assessing the pharmacological properties of antispasmodic agents in vivo. Phenoxybenzamine has an extended action in arterial grafts in vivo. Verapamil/nitroglycerin is short-lived in vivo but lasts longer in vitro. Measurements of antispasmodic duration of action in vitro should be interpreted with caution.     

Cowden's disease

A 24-year old male patient developed multiple lesions of keratoacanthoma in the epidermal verrucous naevus. He also had multiple papillomatous lesions on the lips, buccal mucosa, gingiva and tongue, with positive family history of similar lesions. He also had multiple skin tags and patchy palmoplantar keratoderma and minimal kyphoscoliosis.     

Synthesis of Geopolymer from a Novel Aluminosilicate-Based Natural Soil Precursor Using Electric Oven Curing for Improved Mechanical Strength

Natural soil (NS)-based geopolymers (GPs) have shown promise as environmentally friendly construction materials. The production of ordinary Portland cement is known to release significant amounts of greenhouse gas (CO₂) into the atmosphere. The main objective of this work is to synthesize a geopolymer (GP) from an uncommon aluminosilicate-based NS and a sodium silicate (SS) activating solution that would not only minimize the emission of harmful gases, but also offer improved mechanical strength. Samples of different compositions were produced by varying the wt.% of NS from 50% to 80% and adding a balancing amount of SS solution. The drying and curing of the samples were carried out in an electric oven at specific temperatures. The degree of geopolymerization in the samples was measured by Fourier transform infrared spectroscopy, and microstructural analysis was performed using a scanning electron microscope. Mechanical tests were conducted to evaluate the range of compressive strength values of the prepared GP samples. A minimum compressive strength of 10.93 MPa at a maximum porosity of 37.56% was observed in a sample with an NS to SS ratio of 1:1; while a ratio of 3:1 led to the maximum compressive strength of 26.39 MPa and the minimum porosity of 24.60%. The maximum strength (26.39 MPa) was found to be more than the reported strength values for similar systems. Moreover, an improvement in strength by a factor of three has been observed relative to previously developed NS-based GPs. It may be inferred from the findings that for the given NS, with almost 90% aluminosilicate content, the extent of geopolymerization increases significantly with its increasing proportions, yielding better mechanical strength.     

A comparison of quality of sleep between patients with chronic kidney disease not on hemodialysis and end-stage renal disease on hemodialysis in a developing country

Few studies have compared quality of sleep between pre-dialysis chronic kidney disease (pre-dialysis CKD) patients and end-stage renal disease patients on dialysis (ESRD) and have found inconsistent results. Objective of this study is to compare quality of sleep between patients with pre-dialysis CKD and ESRD in a developing country. This study was conducted in an out-patient department and hemodialysis unit of a tertiary care facility. Patients included had either pre-dialysis CKD or ESRD. Assessment of quality of sleep was done using Pittsburgh sleep quality index (PSQI). A total of 152 patients were included in the study. Out of these patients, 79 (52%) had ESRD and 73 (48%) had pre-dialysis CKD. Median PSQI score was 6 (IQR 3–8.8). Poor sleep quality (PSQI ≥5) was present in 100 (65.8%) patients. Only hemoglobin (β?=??0.39, p?β?=?0.56, p?β?=?0.22, p?r?=??0.34, p value .80) in pre-dialysis CKD patients. Poor sleep quality is common in patients with CKD including hemodialysis patients in a developing country, which is independent of kidney function in non-dialysis patients. There is no difference in quality of sleep between pre-dialysis CKD and ESRD patients.