Elastic liposome-based gel for topical delivery of 5-fluorouracil: in vitro and in vivo investigation.

OBJECTIVE: This investigation has focused to characterize the elastic liposome containing 5-fluorouracil (5-FU) and to enhance drug permeation across stratum corneum (SC) of the skin (rat) using various surfactants and in vivo dermal toxicity evaluation. METHODOLOGY: 5-FU-loaded elastic liposomes were developed, prepared and characterized for their entrapment efficiency, vesicle size, number of vesicles, morphological characteristics, surface charge and turbidity. In vitro drug release profile, in vitro skin permeation potential and in vitro hemolytic ability of the formulation have been evaluated to compare with drug solution for 24 h. In vitro skin permeation potential was also compared with marketed cream. Furthermore, in vivo skin irritation potential, drug penetration into the skin using confocal laser scanning microscopy (CLSM) and in vivo toxicity studies were performed. RESULTS AND CONCLUSIONS: The optimized elastic liposomes demonstrated maximum drug entrapment efficiency, optimum vesicular size and considerable elasticity. In vitro skin permeation studies showed the highest drug permeation flux like 77.07 ± 6.34, 89.74 ± 8.5 and 70.90 ± 9.6 µg/cm(2)/h for EL3-S60, EL3-S80 and EL3-T80, respectively, as compared to drug solution (8.958 ± 6.9 µg/cm(2)/h) and liposome (36.80 ± 6.4 µg/cm(2)/h). Drug deposition of optimized elastic liposome EL3-S80 was about three fold higher than drug solution. Skin irritation and CLSM studies suggested that optimized gel was free from skin irritation and capable to deliver 5-FU into the epidermal area for enhanced topical delivery than drug solution. The in vitro study showed minimum hemolysis in the optimized formulation. Finally, in vivo toxicity studies followed with hisptopathological assessment showed that elastic liposome was able to extract SC to improve drug permeation without changing general anatomy of the skin.

Frequency of HIV infection amongst children with disseminated tuberculosis and tuberculous meningitis in Aligarh (North India) - a low HIV prevalence area.

OBJECTIVE: To determine frequency of HIV in children with disseminated tuberculosis and tuberculous meningitis in a low HIV prevalence area, and to study clinical profile of those found HIV positive. STUDY DESIGN: Cross-sectional, descriptive study. PLACE AND DURATION OF STUDY: Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India from February 2005 to January 2008. METHODOLOGY: The study was conducted on 215 children under 14 years of age with either disseminated tuberculosis or tuberculous meningitis. HIV infection was diagnosed in accordance with WHO strategy II. In children younger than 18 months, the strategy (to cut down costs) was to screen first by HIV antibody testing and subject only positive cases to virological tests. Parents of HIV positive children were also tested for HIV and counselled. The clinical profile of HIV positive patients was noted. RESULTS: The frequency of HIV was 5.12%, while that in cases of disseminated tuberculosis was much higher (22%). No case with isolated tuberculous meningitis was HIV positive. The majority (45.45%) of patients with HIV were between 1-5 years of age. The mode of infection in 7 (63.63%) cases was parent to child transmission. Loss of weight, prolonged fever, pallor, hepato-splenomegaly and oral candidiasis were the commonest clinical manifestations among HIV positive patients. CONCLUSION: Clinically directed selective HIV screening in cases of disseminated tuberculosis can pickup undiagnosed cases of the same in areas with low prevalence of HIV infection.

Localization of a novel autosomal recessive non-syndromic hearing impairment locus (DFNB38) to 6q26-q27 in a consanguineous kindred from Pakistan.

For autosomal recessive nonsyndromic hearing impairment over 30 loci have been mapped and 19 genes have been identified. DFNB38, a novel locus for autosomal recessive nonsyndromic hearing impairment, was localized in a consanguineous Pakistani kindred to 6q26-q27. The affected family members present with profound prelingual sensorineural hearing impairment and use sign language for communications. Linkage was established to microsatellite markers located on chromosome 6q26-q27 (Multipoint lod score 3.6). The genetic region for DFNB38 spans 10.1 cM according to the Marshfield genetic map and is bounded by markers D6S980 and D6S1719. This genetic region corresponds to 3.4 MB on the sequence-based physical map.