Multiple emulsions: an overview

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.     

Profile of Kangari cancer: a prospective study

Kangari, an earthenware brazier containing burning charcoal, is used for personal warming during the winter months by most of the people in Kashmir valley. Kangari is usually held close to the lower abdomen or in between the legs while squatting on the ground. The use of kangari is associated with development of skin cancer at the sites of prolonged exposure. In the present study 43 patients with Kangari cancer were analyzed prospectively with the objective of understanding their clinico-pathological profile and the response to various treatment modalities. Variables such as age, gender, grade, site of lesion etc., were evaluated for their prognostic significance.     

Profile of amblyopia in a hospital referral practice

OBJECTIVE: Evaluation of the clinical profile and distribution of different sub-types of amblyopia in a referral eye hospital in India. METHODS: This was a prospective hospital-based observational study, evaluating the clinical profile of patients with amblyopia presenting to a referral strabismology practice. The examination included assessment of the visual acuity, the refractive status, the fixation pattern, the grade of binocularity, and evaluation of the associated strabismus, if any before treatment was started. RESULTS: The average age of the patients at presentation was 7.97?6.18 years with 81 out of 683 patients (11.8%) presenting above the age of 20 years. The best-corrected visual acuity (BCVA) was less than 6/60 in the amblyopic eye in 121 out of 733 eyes (16.5%). Strabismic amblyopia was the most common sub-type of amblyopia seen (274/733 eyes, 37.38%). Though patients with anisometropic amblyopia presented at a later age (average of 10.03+/-6.92 years), they had better visual acuity, binocular functions, and centricity of fixation at all ages, relative to other sub-types of amblyopia. The BCVA did not show any co-relation with the age of presentation [co-relation co-efficient (CF) of 0.074], refractive status of the amblyopic eye (CF of 0.078), the type of amblyopia (CF of 0.196), or the type of strabismus present (CF of 0.079). However, a very significant co-relation was seen between the BCVA and the fixation pattern of the amblyopic eye (CF of 0.817). CONCLUSIONS: Lack of knowledge and awareness about amblyopia and its appropriate timely management has been the main cause for the late presentations and significant visual impairment associated with the condition.     

Apolipoprotein E enrichment of immuno-separated chylomicron and chylomicron remnants following saturated fatty acids

AimWe examined the effect of meal fatty acids on lipid and apolipoprotein concentrations of very low density lipoprotein (VLDL) and chylomicron/chylomicron remnants in lipid fractions with a Svedberg flotation rate (S_f) 60–400 and S_f 20–60.Methods and resultsSix healthy middle-aged men received in random order mixed meals enriched with saturated (SFA), polyunsaturated (PUFA) or monounsaturated (MUFA) fatty acids on 3 occasions. VLDL and chylomicron/chylomicron remnants in the lipid fractions were separated by immunoaffinity chromatography against apo B-100. In the S_f 60–400 chylomicron/chylomicron remnants, triacylglycerol and cholesterol concentrations were significantly lower following PUFA compared with SFA and MUFA (P ≤ 0.05). Apolipoprotein (apo) E responses were significantly higher after SFA in chylomicron/chylomicron remnants and VLDL compared with PUFA and MUFA (P < 0.007). However, apo B responses (particle number) were higher following MUFA than SFA (P = 0.039 for chylomicron/chylomicron remnants). Composition of the chylomicron/chylomicron remnants (expressed per particle) revealed differences in their triacylglycerol and apo E contents; in the S_f 60–400 fraction, SFA-rich chylomicron/chylomicron remnants contained significantly more triacylglycerol than MUFA (P = 0.028), more apo E than PUFA- and MUFA-rich particles (P < 0.05) and in the S_f 20–60 fraction, more apo E than MUFA (P = 0.009).ConclusionThere are specific differences in the composition of chylomicron/chylomicron remnants formed after saturated compared with unsaturated fatty acid-rich meals which could determine their metabolic fate in the circulation and subsequent atherogenicity.     

Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase

In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation.     

The shear bond strength of acetone and ethanol-based bonding agents to bleached teeth

PURPOSE: The purpose of this in vitro study was to evaluate the: (1) shear bond strength (SBS) of acetone and ethanol-based bonding agents to composite resin 24 hours after being bleached with 35% hydrogen peroxide; and (2) interface morphology and mode of fracture (IMMF) between composite resin and enamel. METHODS: Forty extracted teeth were randomly assigned into 4 groups: (1) group 1: 35% H2O2 + acetone; (2) group 2: H2O2 + ethanol; (3) group 3: acetone; (4) group 4: ethanol. All teeth were acid etched, bonding agents were applied, and a composite resin stub was bonded and stored again in saline for 24 hours. SBS was determined, and scanning electron microscopy (SEM) was used for IMMF evaluation. RESULTS: SBS was significantly lower in bleached than unbleached teeth (P < .001), but SBS did not differ between the acetone-based or ethanol-based adhesives (P = .55) and bleaching did not interact with adhesive treatment (P = .39). IMMF analysis of the unbleached teeth showed a continuous interface between the resin and enamel. By contrast, bleached teeth showed sparse contact between the resin and enamel and the resin was poorly infiltrated into the enamel surface. CONCLUSION: Morphologic changes in human tooth enamel, 24 hours after bleaching, were associated with a reduction in the shear bond strength of adhesives.     

Insulin reduces the multiple organ injury and dysfunction caused by coadministration of lipopolysaccharide and peptidoglycan independently of blood glucose: role of glycogen synthase kinase-3beta inhibition

OBJECTIVE: Insulin reduces morbidity and mortality among critically ill patients, but the molecular mechanisms of its effect remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3, which may play an important role in systemic inflammation and shock. Here we investigate the role of blood glucose and glycogen synthase kinase-3beta inhibition in the protective effect of insulin on the organ injury/dysfunction associated with excessive systemic inflammation. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: Eighty-five anesthetized Wistar rats. INTERVENTIONS: Rats received Escherichia coli lipopolysaccharide (1 mg/kg) and Staphylococcus aureus peptidoglycan (0.3 mg/kg) or vehicle intravenously. Insulin (1.4 units/kg intravenously) was administered in the absence or presence of continuous glucose administration (4.5 mg/kg/hr intravenously) either prophylactically or therapeutically. The potent and selective glycogen synthase kinase-3beta inhibitor TDZD-8 (1 mg/kg intravenously) or vehicle (10% dimethyl sulfoxide) was administered either prophylactically or therapeutically. MEASUREMENTS AND MAIN RESULTS: Coadministration of lipopolysaccharide and peptidoglycan resulted in increases in the serum levels of creatinine (indicator of renal dysfunction), alanine aminotransferase, and aspartate aminotransferase (indicators of liver injury) at 6 hrs. Insulin or TDZD-8 similarly attenuated the organ injury/dysfunction caused by lipopolysaccharide and peptidoglycan when given either prophylactically or therapeutically. Continuous glucose administration had no effect on blood glucose levels or organ injury/dysfunction at 6 hrs. Treatment with insulin or TDZD-8 reduced the plasma levels of the proinflammatory cytokine interleukin-1beta. In vitro, insulin or TDZD-8 caused similar reductions in the nuclear factor-kappaB p65 activity and similar increases in the phosphorylation of Ser9 of glycogen synthase kinase-3beta. CONCLUSIONS: Therapy with insulin or the potent and selective glycogen synthase kinase-3beta inhibitor TDZD-8 reduced the organ injury/dysfunction caused by lipopolysaccharide and peptidoglycan in the rat. We propose that the inhibitory effect of insulin on the activity of glycogen synthase kinase-3beta contributes to the protective effect of insulin against the organ injury/dysfunction caused by excessive systemic inflammation independently of any effects on blood glucose.