Effect of 3-methylcholanthrene pretreatment on 2-acetylaminofluorene n- and ring-hydroxylation by rat and hamster liver microsomes

The N- and ring-hydroxylation of 2-acetylaminofluorene (AAF) are studied with microsomal fractions of livers from both control and 3-methylcholanthrene (MC)-pretreated rats and hamsters. The profiles of hydroxylations are similar in the presence of either low (2.3 μM) or high (100 μM) substrate concentrations. Pretreatment of rats gives a severalfold increase both in N- and ring-hydroxylation, whereas m hamsters, such a pretreatment induces a specific and large increase in N-hydroxylation only.     

Comparative potency of formulations of mometasone furoate in terms of inhibition of 'PIRHR' in the forearm skin of normal human subjects measured with laser doppler velocimetry

BACKGROUND AND AIMS: Topical glucocorticoid formulations are widely used for effective treatment and control of a variety of dermatoses. Mometasone furoate is a newer corticoid that has high potency but low systemic toxicity. Pharmaceutical factors are known to significantly influence potency and systemic absorption of topically applied glucocorticoids. We studied the potency of "Elocon", a topical formulation of mometasone furoate, compared with two other branded formulations of the same corticoid. METHODS: Corticoid potency was measured by employing a pharmacodynamic parameter of an inhibitory effect of the corticoid on post-ischemic-reactive-hyperemic-response (PIRHR) in human forearm skin under occlusive dressing. The PIRHR was expressed in terms of % increase in the skin blood flow (SBF) as measured with laser doppler velocimetry (LDV). RESULTS : All three active branded formulations of mometasone furoate produced significant inhibition of PIRHR. The AUC(0-2 min) of PIRHR was ( Mean +/- SEM ), Control = 213.52 +/- 11.80, Placebo = 209.77 +/- 19.31, Formulation A = 119.83 +/- 13.71, Formulation C = 53.67 +/- 4.85 and Formulation D = 111.46 +/- 22.87. Formulation "C" exhibited significantly higher topical anti-inflammatory potency than formulations "A" or "D". CONCLUSIONS: Thus, branded formulations of the same glucocorticoid, mometasone furoate significantly differed in their topical anti-inflammatory potency. "Elocon" was significantly more potent than the two other branded formulations studied.     

Hyperhomocysteinemia as a risk factor for ischemic stroke: an Indian scenario

BACKGROUND: Hyperhomocysteinemia has been proposed as an important risk factor for ischemic stroke worldwide, but data available from the Indian subcontinent is scarce. AIM: To study homocysteine levels in patients with ischemic stroke and compare it with age- and sex-matched controls. SETTINGS AND DESIGN: Case-control prospective study. MATERIALS AND METHODS: Fifty-seven patients with ischemic stroke and 30 controls were recruited for the study. They were subdivided into two subgroups (< 40 years and> 40 years of age) and plasma fasting total homocysteine (tHcy) levels were measured. STATISTICAL ANALYSIS USED: Student's 't' test and chi-square test. RESULTS: The tHcy were significantly high in patients with stroke, compared to controls (9.91 +/- 2.25 vs 8.00 +/- 2.74 micromol/l; P vs 8.45 +/- 2.72 micromol/l; P = 0.01) and female patients compared to controls (9.08 +/- 1.81 vs 6.79 +/- 2.60 micromol/l; P = 0.04). The tHcy levels were significantly high in patients with hypertension compared to normotensive patients (10.96 vs 9.49 micromol/l; P = 0.01) and smokers compared to nonsmokers (11.17 vs 9.33 micromol/l; P = 0.01). CONCLUSIONS: Hyperhomo-cysteinemia emerged as an important independent risk factor for ischemic stroke. A strong positive correlation was also observed between hypertension, smoking, and high-tHcy levels in the present study.     

Living donor transplantation of a pelvic kidney

Pelvic kidneys are uncommon anomalies rarely utilized in kidney transplantation. We describe a successful case of living-donor transplantation using a pelvic kidney in a 17-month-old infant with congenital renal dysplasia. The recipient had exhausted all options for renal replacement therapy, and urgent transplantation was considered a life saving treatment.     

Paraganglioma of the urinary bladder--a case report

Paragangliomas of the urinary bladder are extremely rare tumors accounting for less than 1% of all bladder tumors. Males and females are affected roughly equally with an average age of 41 years. Hypertension and headache during or immediately after voiding in association with intermittent hematuria is virtually diagnostic of urinary bladder paragangliomas. A high index of clinical suspicion is required to diagnose these tumors. We present a case of a urinary bladder paraganglioma because of its rarity.     

CO(2) and pH independently modulate L-type Ca(2+) current in rabbit carotid body glomus cells

The carotid bodies respond to changes in arterial O(2), CO(2), and pH, and Ca(2+) influx via voltage-gated Ca(2+) channels is an important step in the chemoreception process. The objectives of the present study were as follows: 1) to determine whether hypercapnia modulates Ca(2+) current in glomus cells, and if so, to determine if this modulation is secondary to changes in pH; 2) to examine the mechanism of CO(2) modulation of the Ca(2+) current; and 3) to determine whether the effects of hypercapnia and hypoxia on Ca(2+) channel activity in glomus cells are synergistic. The effects of CO(2) on Ca(2+) current were monitored in glomus cells isolated from rabbit carotid bodies using both perforated and conventional patch-clamp techniques. Raising CO(2) in the extracellular solution from 5 to 10% (hypercapnia) reversibly augmented the whole-cell Ca(2+) current. This augmentation was rapid and increased the whole-cell Ca(2+) current similarly in both the perforated and the conventional patch configurations by 16 +/- 2% (n = 5) and 15 +/- 1% (n = 32), respectively. The following observations suggest that the effects of CO(2) are not secondary to changes in pH: 1) isohydric hypercapnia (pH maintained at 7.4) augmented the Ca(2+) current by 24 +/- 2% (n = 6); 2) decreasing the pH of the extra- or intracellular solutions decreased the Ca(2+) current by 43 +/- 4% (n = 8) and 13 +/- 1% (n = 5), respectively; and 3) hypercapnia did not shift the half-maximal activation voltage (V(1/2)), whereas intracellular and extracellular acidosis alone caused shifts in V(1/2). Furthermore, 100 nM of a membrane-permeable protein kinase A inhibitor prevented the augmentation by CO(2), and 500 microM 8-Br-cAMP mimicked the effect of CO(2) by augmenting the Ca(2+) current by 10 +/- 2% (n = 6). Also, cyclic AMP levels in carotid bodies increased from 1.98 +/- 0.6 to 9.0 +/- 2 pmol/microg protein in response to hypercapnia. In contrast, decreasing pH in the nominal absence of CO(2) did not affect cAMP levels in rabbit carotid bodies. Further, nisoldipine, but not omega-conotoxin MVIIC, prevented augmentation of the Ca(2+) current by CO(2). In addition, when combined, hypercapnia and hypoxia augmented the Ca(2+) current by 26 +/- 4% (n = 7), which is greater than either stimulus alone, suggesting the effects are additive. Taken together, these results indicate that L-type Ca(2+) current is augmented by hypercapnia. The effect of CO(2) is not secondary to changes in pH and seems to be mediated by a protein kinase A-dependent mechanism. Furthermore, hypercapnia and hypoxia act additively in stimulating Ca(2+) current in glomus cells.