Formulation, preclinical and clinical evaluation of a new submicronic arginine respiratory fluid for treatment of chronic obstructive pulmonary disorder.

Inhalational drugs often suffer from low pulmonary deposition due to their micronized size. Aim of present study was development and evaluation of a novel submicronic L-arginine respiratory fluid formulation for treatment of cardiopulmonary complications associated with chronic obstructive pulmonary disorder (COPD). Objectives were (a) to develop and characterize submicronic L-arginine respiratory fluid formulation, (b) pre-clinical safety/toxicity study in 2-animal species, (c) in vitro and in vivo evaluation in terms of respiratory fraction, and (d) clinical study to assess safety/efficacy in healthy volunteers/COPD patients. Formulation was optimized on the basis of particle size of aerosolized medication with particle size in the range of 400-500 nm. Anderson cascade impaction (ACI) studies were performed to validate the advantage in terms of respirable fraction, which indicated a high respirable fraction (51.61 ± 3.28) for the developed formulation. In vivo pulmonary deposition pattern of optimized formulation was studied using gamma scintigraphy in human volunteers using (99m)Tc-arginine as radiotracer. It clearly demonstrated a significant pulmonary deposition of the submicronic formulation in various lung compartments. Efficacy of the developed formulation was further assessed in COPD patients (n = 15) by evaluating its effect on various cardiopulmonary parameters (spirometry, pulse-oxymetry, echocardiography and 6-min walk test). A marked improvement was seen in patients after inhalation of submicronic arginine in terms of their cardiopulmonary status. Results suggest that submicronic arginine respiratory fluid has the potential to be developed into an attractive therapeutic option for treating COPD associated cardiopulmonary complications.

The role of T-lymphocyte subsets and interleukin-5 blood levels among Indian subjects with autoimmune thyroid disease.

OBJECTIVE: Autoimmune Thyroid Disease (AITD) results from an interaction of exogenous and endogenous factors in a genetically predisposed individual. AITD is being increasingly reported among the Indian population. Lymphocyte subsets and levels of interleukin-5 (IL- 5) were studied in the peripheral blood of patients with AITD. DESIGN: Subjects diagnosed with either hyperthyroidism due to Graves' Disease (GD) or with primary hypothyroidism due to Hashimoto's Thyroiditis (HT) were consecutively recruited. Euthyroid controls were also recruited for comparison. Lymphocyte subsets (CD4 and CD8 counts, CD4/CD8 ratio) were evaluated by flow cytometry and IL-5 levels were determined by the sandwich ELISA method. RESULTS: Nineteen subjects with GD, 16 subjects with HT and 10 controls were studied. CD4/CD8 ratios were found to be significantly lower only in subjects with HT compared to controls. Serum IL-5 values were significantly higher in both GD and HT in comparison to controls. CONCLUSIONS: The study found increased levels of IL-5 and reduction in ratios of CD4/CD8 lymphocytes in the peripheral blood of patients with HT, but only IL-5 was increased in GD. High levels of IL-5 could have resulted in the high titres of antithyroid antibodies and may therefore be considered to play a more significant role than peripheral lymphocytes in the pathogenesis of AITD in the Indian population.

Tubercular Thyroiditis as a Part of Disseminated Tuberculosis in a Young Male: A Rare Clinical Presentation.

Thyroid tuberculosis is uncommon even in countries like India where prevalence of tuberculosis is high. Bactericidal actions of colloid, excess iodine stores and high vascularity of the gland have been implicated for the very rare occurrence of thyroid tuberculosis. We present a case of a 16-year-old male with thyroid involvement as a part of disseminated tuberculosis. The clinical presentation of thyroid tuberculosis is varied and may be missed if not kept in the differential diagnosis of goitre. This case also highlights the role of fine needle aspiration cytology in management of goitre. It is an important diagnostic test as it avoids unnecessary surgical intervention.

Goitrous autoimmune thyroiditis in a pediatric population: a longitudinal study.

BACKGROUND: Patients with autoimmune thyroiditis can present with thyroid function that varies from euthyroidism to frank hypothyroidism or occasionally hyperthyroidism. Although there is a risk of progression from the euthyroid or subclinical hypothyroid state to frank hypothyroidism, the rate of progression is not known. OBJECTIVES: Subjects with diffuse goiter and autoimmune thyroiditis were followed up to observe the rate of deterioration in thyroid function from euthyroid and subclinical hypothyroid states to hypothyroidism. METHODS: Patients who presented with goiter and autoimmune thyroiditis were grouped as those with euthyroidism, subclinical hypothyroidism, and overt hypothyroidism on the basis of levels of thyroxine and thyrotropin at presentation. Patients were followed up for a minimum duration of 24 months with periodic monitoring of thyroid function. RESULTS: Ninety-eight consecutive subjects (aged of 8-18 years) with a diagnosis of autoimmune thyroiditis and diffuse goiter were studied. At presentation, in 24 subjects (24.5%) thyroid function was normal (euthyroidism), 32 (32.6%) had subclinical hypothyroidism, and the remaining 42 subjects (42.9%) had hypothyroidism. All of the subjects with hypothyroid were maintained euthyroid on thyroxine during follow-up. Hypothyroidism developed in 3 of 24 patients with euthyroidism and in 4 of 32 patients with subclinical hypothyroidism. CONCLUSIONS: Subjects with goitrous autoimmune thyroiditis need periodic monitoring of thyroid function. Development of thyroid dysfunction is insidious and may not be accompanied by symptoms and clinical signs. In pediatric and adolescent age groups it is imperative to correct thyroid dysfunction to achieve optimal growth and development.

Sodium bicarbonate-augmented stress thallium myocardial scintigraphy.

It is well known that sodium bicarbonate in pharmacological doses induces transient alkalosis, causing intracellular transport of serum potassium. The aims of this study were (a) to investigate whether, in humans, myocardial thallium-201 uptake can be augmented by pretreatment with a single bolus of sodium bicarbonate at a pharmacological dose, (b) to verify general safety aspects of the intervention and (c) to evaluate the clinical implications of augmentation of (201)Tl uptake, if any. Routine exercise myocardial scintigraphy was performed twice in eight adult volunteers (five normal and three abnormal), once without intervention and the second time (within a week) following intravenous administration of sodium bicarbonate (88 mEq in 50 ml) as a slow bolus 1 h prior to the injection of (201)Tl. Conventional myocardial thallium study was compared with sodium bicarbonate interventional myocardial scintigraphy with respect to myocardial uptake (counts per minute per mCi injected dose), washout patterns in normal and abnormal myocardial segments, and overall clinical interpretation based on planar and single-photon emission tomographic (SPET) images. All patients remained asymptomatic after the intervention. A mean increase of 53% in myocardial uptake of thallium was noted in post-exercise acquisitions after the intervention, confirming uptake of the tracer via the potassium-hydrogen pump and its augmentation by transient alkalosis. The washout pattern remained unchanged. The visual quality of planar and SPET images improved significantly after the intervention. Out of the five abnormal myocardial segments identified in three cases, four showed significant filling-in after the intervention, causing the diagnosis to be upgraded from "partial scar" to "ischaemia", or from "ischaemia" to "normal". The overall scan impression changed in two out of three such cases. Sodium bicarbonate augmentation may have significant implications for stress-thallium scintigraphy and may be a new parameter for defining myocardial viability.