Experiences with Mycobacterium leprae soluble antigens in a leprosy endemic population

Rees and Convit antigens prepared from armadillo-derived Mycobacterium leprae were used for skin testing in two leprosy endemic villages to understand their use in the epidemiology of leprosy. In all, 2602 individuals comprising 202 patients with leprosy detected in a prevalence survey, 476 household contacts and 1924 persons residing in non-case households were tested with two antigens. There was a strong and positive correlation (r = 0.85) between reactions to the Rees and Convit antigens. The distribution of reactions was bimodal and considering reactions of 12 mm or more as 'positive', the positivity rate steeply increased with the increase in age. However, the distributions of reactions to these antigens in patients with leprosy, their household contacts and persons living in non-case households were very similar. These results indicate that Rees and Convit antigens are not useful in the identification of M. leprae infection or in the confirmation of leprosy diagnosis in a leprosy endemic population with a high prevalence of nonspecific sensitivity.     

Use of Ponseti's technique in recurrent clubfeet following Kite's method of correction

We report the results of 18 recurrent clubfeet in 13 children after Kite's method of casting treated successfully by Ponseti's technique. The average age was 8.3 months. The average preoperative Pirani's midfoot contracture score was 1.8, hindfoot contracture score was 2.4, and total score was 4.2. All patients had full correction of deformities with plantigrade feet and the scores were reduced to zero at the end of treatment. Three recurrences were found at 6 months follow-up, amounting to 17% failure rate. Two of them necessitated percutaneous tenotomy of the tendoachilles, and one underwent posteromedial soft tissue release with good result at the end of 1 year. Ponseti's method is an effective treatment option in the management of recurrent clubfeet after Kite's method. Although short-term results are promising, larger series with long-term follow-up is warranted.     

Pharmacokinetics and pharmacodynamics of drospirenone-estradiol combination hormone therapy product coadministered with hydrochlorothiazide in hypertensive postmenopausal women

The effects of combination hormone therapy of drospirenone (DRSP), a novel progestin with antialdosterone properties, and 17beta-estradiol (E2) on hydrochlorothiazide (HCTZ) pharmacokinetics/pharmacodynamics versus placebo were investigated in a double-blind, placebo-controlled, crossover study. Thirty-six postmenopausal women with stage 1 hypertension maintained on 25 mg of HCTZ once daily were randomized to receive either 3 mg of DRSP/1 mg of E2 or placebo once daily for 4 weeks. Plasma HCTZ, serum DRSP, E2, potassium, aldosterone, and plasma renin activity were determined at baseline and after 4 weeks. Results showed that the combination of DRSP/E2 plus 25 mg of HCTZ is safe and well tolerated in hypertensive postmenopausal women. The pharmacokinetics of HCTZ were not affected by coadministration of DRSP/E2. The geometric mean ratios and 90% confidence intervals ([HCTZ + DRSP/E2]/[HCTZ + placebo]) for HCTZ (a) area under the serum/plasma concentration-time curve from 0 to 24 hours and (b) maximum plasma concentration were 101 (90.7, 112) and 103 (92.8, 115), respectively. In the HCTZ + DRSP/E2 group, serum potassium, aldosterone, and plasma renin activity all increased in a manner marginally consistent with a beneficial antialdosterone effect, counteracting the HCTZ-induced potassium loss and lowering both systolic and diastolic blood pressure. No dose adjustment is required when DRSP/E2 is added to antihypertensive therapy with HCTZ in hypertensive postmenopausal women.     

Opposing effects on immune function and skin barrier regulation by the proteasome inhibitor bortezomib in an allergen‐induced eczema model

Proteasome inhibition (PI) has been reported to interfere with antibody‐driven autoimmune diseases. The impact of PI on the allergic immune response and on skin diseases like atopic dermatitis (AD) has not been thoroughly explored, however. Here, we examined whether the PI bortezomib interferes with the allergic immune response and the severity of AD by using an established mouse model of allergen‐driven dermatitis, to which bortezomib was applied after the establishment of systemic sensitization to ovalbumin. The treatment indeed resulted in a remarkable decrease in total and allergen‐specific plasma cells/antibody‐secreting cells, as evidenced by flow cytometry and ELISpot, respectively. This was accompanied by rapid reductions in serum antibody titres, including a prominent reduction of the IgE isotype. CD4+ and CD8+ cells were greatly diminished in lesional skin on immunohistological staining. The impressive effects at the level of immune modulation did not result in any improvement in the eczema, however. Following up on this unexpected result, we found that the skin itself was susceptible to bortezomib, by which it was instructed to lower the expression of critical skin barrier genes, especially transglutaminase‐1 and filaggrin. Together, bortezomib eliminates plasma cells and decreases immunoglobulin responses, including allergenic IgE. Although anti‐inflammatory effects are detectable in the skin, counter‐regulatory effects from PI on resident skin cells likely undermine improvement in the eczema. These results caution against the therapeutic use of bortezomib for inflammatory skin disorders, which are characterized by inherently impaired barrier function, especially AD.     

Nicotine gum-induced atrial fibrillation

A 39-year-old man with no prior history of atrial fibrillation was hospitalized with atrial fibrillation and a rapid ventricular rate. For the 7 months before presentation, he had been chewing nicotine polacrilex gum on his own. The week he first developed palpitations, he was chewing more than 1 piece of nicotine Polacrilex gum per hour during work. His diagnostic work-up during hospitalization found no cause for atrial fibrillation. He was cardioverted to sinus rhythm. At 6-month follow-up, he had not renewed chewing nicotine polacrilex gum, was in sinus rhythm, and had no history of palpitations. The temporal relation between more frequent gum usage and the excessive consumption of nicotine polacrilex chewing gum with a probable high serum nicotine level at the time the patient developed his first episode of atrial fibrillation suggests a causal relationship.     

A comparative pharmacological and phytochemical analysis of in vivo & in vitro propagated Crotalaria species

ObjectiveTo compare the efficacy for phytochemical, antibacterial and antioxidant activities of petroleum ether, chloroform, ethanol, and aqueous extracts of in vitro propagated plants and field grown plants of Crotalaria sps., for against five human pathogens.MethodsThe preliminary phytochemistry, antimicrobial and antioxidant activities were evaluated using disc diffusion and DPPH radical scavenging methods.ResultsThe ethanolic extract of in vitro raised Crotalaria retusa (C. retusa) was effective on tested microorganisms and optimal ZOI values of 38 mm was obtained against Pseudomonas aeruginosa (P. aeruginosa). The optimal concentration (IC50) required for 50% inhibition of the DPPH radical scavenging was 57.6 μ g/mL obtained for ethanolic extract of in vitro propagated C. retusa. The in vitro propagated C. retusa has significant pharmacological activities while the Crotalaria prostrate (C. prostrate) and Crotalaria medicaginea (C. medicaginea) has low pharmacological activites. It was cleared that ethanolic extract of in vitro regenerated plants was most effective.ConclusionsThese findings indicate compounds isolated from ethanolic extracts of Crotalaria sps., possesses pharmacological properties and potential to develop natural compounds based pharmaceutical products. The IC₅₀ values for ethanolic extracts of Crotalaria sps. was evaluated through the Linear regression analysis (R² ≤ 1).     

Functional roles of the phosphatidylinositol 3-kinases (PI3Ks) signaling in the mammalian ovary

The proinflammatory status of adipose tissue has been linked to the metabolic and cardiovascular consequences of obesity. Human adipose cells express the calcium sensing receptor (CaSR), and its expression is elevated in inflammatory states, such as that associated with obesity. Given the CaSR's association with inflammation in other tissues, we evaluated its role elevating the adipose expression of inflammatory factors. The CaSR activation by the calcimimatic cinacalcet (5μM) in adipose tissue and in vitro cultured LS14 adipose cells elicited an elevation in the expression of the proinflammatory cytokines IL6, IL1β, TNFα, and the chemoattractant CCL2. This was in part reverted by SN50, an inhibitor of the inflammatory mediator nuclear factor kappa B (NFκB). Our observations suggest that CaSR activation elevates cytokine and chemokine production, partially mediated by NFκB. These findings support the relevance of the CaSR in the pathophysiology of obesity-induced adipose tissue dysfunction, with an interesting potential for pharmacological manipulation.     

Clinical presentation of microbial keratitis with daily wear frequent-replacement hydrogel lenses: a case series.

Microbial keratitis (MK) is a serious complication associated with contact lens wear. In this case series we report three clinical presentations of MK associated with daily-wear monthly-replacement soft contact lenses. All of these patients were using vifilcon A (55% water content, ionic, U.S. Food and Drug Administration [FDA] group IV) monthly-replacement soft contact lenses. A gram-stained smear of the corneal scrapings of two patients showed numerous gram-negative cocci bacilli, and tissue cultures showed significant growth of Pseudomonas aeruginosa. In the third patient, the corneal scrapings showed numerous gram-negative bacilli, along with gram-positive cocci, and tissue culture showed significant growth of Aeromonas species and alpha-hemolytic streptococci. All these cases were resolved by medical therapy. This case series highlights the importance of patient symptoms, clinical features, and microbiologic work-up in making a differentiation between MK and sterile contact lens-induced peripheral ulcer (CLPU). A high index of suspicion and close follow-up care will avoid misdiagnosis and reduce complications.     

An improved and validated LC method for resolution of bicalutamide enantiomers using amylose tris-(3,5-dimethylphenylcarbamate) as a chiral stationary phase

An improved HPLC method for determination of enantiomeric purity of bicalutamide in drugs and pharmaceuticals was developed and validated. Baseline separation with resolution >/=6.0 was achieved within 10 min on Chiralpak AD-H (250 mm x 4.6 mm; particle size 5 microm) column using n-hexane:2-propanol (65:35 v/v) as mobile phase at a flow rate of 1.0 ml/min at 25 degrees C. The detection was made at 270 nm using UV detector while a polarimetric detector connected in series was used for identification of enantiomers. The effects of 2-propanol, ethanol and temperature on enantioselectivity and resolution of enantiomers were evaluated. The method was validated in terms of accuracy, precision and linearity in the range of 10-250 microg/ml and the r(2) was >0.9999. The recoveries were 99.68-100.25% with <1% R.S.D. The limits of detection (LOD) and quantification (LOQ) of enantiomers were (2.4, 3.0 and 7.6, 9.3) x 10(-8)g/ml for (S)-(+)-BCT and (R)-(-)-BCT enantiomers, respectively. The method was found to be suitable for rapid determination of enantiomeric purity of bicalutamide in bulk drugs and pharmaceutical formulations.