A Discursive Review of Recent Development and Patents on Glycerosomes.

BACKGROUND: To achieve a target-based drug delivery with minimal side effects, novel drug delivery systems are being continuously explored. Vesicular systems are one such system that can ameliorate the bioavailability of the encapsulated drug by delivering the drug at the targeted site and can minimize the side effect. OBJECTIVE: The objective of this patent review is to provide a vivid description of glycerosomes and their applications. Glycerosomes are sphere-shaped versatile vesicles consisting of one or more phospholipid bilayers similar to liposomes but contain a high concentration of glycerol, which modifies the liposome bilayer fluidity. Glycerosomes can encapsulate both hydrophobic and hydrophilic drugs, which makes them the promising vehicle in the field of drug delivery. CONCLUSION: Most of the glycerosome formulations prepared were targeted for topical delivery and in particular, a cutaneous route where they have shown promising results. These vesicles are biocompatible and due to the high glycerol concentration, they have improved spreadability and penetrability. It is therefore imperative to explore the other topical routes such as ocular, vaginal, nasal, and rectal for delivery of drugs.

Efficiency of vanillin in impeding metabolic adaptability and virulence of Candida albicans by inhibiting glyoxylate cycle, morphogenesis, and biofilm formation.

BACKGROUND AND PURPOSE: Candida albicans is the fourth most common cause of nosocomial fungal infections across the world. The current drug regimens are suffering from such drawbacks as drug resistance, toxicity, and costliness; accordingly, they highlight the need for the discovery of novel drug agents. The metabolic adaptability under low-carbon conditions and expression of functional virulence traits mark the success of pathogens to cause infection. The metabolic pathways, such as glyoxylate cycle (GC), enable C. albicans to survive under glucose-deficient conditions prevalent in the hostile niche. Therefore, the key enzymes, namely isocitrate lyase (ICL) and malate synthase (MLS), represent attractive agents against C. albicans. Similarly, virulence traits, such as morphogenesis and biofilm formation, are the crucial determinants of C. albicans pathogenicity. Regarding this, the present study was conducted to uncover the role of vanillin (Van), a natural food flavoring agent, in inhibiting GC, yeast-to-hyphal transition, and biofilm formation in human fungal pathogen C. albicans. MATERIALS AND METHODS: For the determination of hypersensitivity under low-glucose conditions, phenotypic susceptibility assay was utilized. In addition, enzyme activities were estimated based on crude extracts while in-silico binding was confirmed by molecular docking. The assessment of morphogenesis was accomplished using hyphal-inducing media, and biofilm formation was estimated using calcofluor staining, MTT assay, and biomass measurement. Additionally, the in vivo efficacy of Van was demonstrated using Caenorhabditis elegans nematode model. RESULTS: Based on the results, Van was found to be a potent GC inhibitor that phenocopied ICL1 deletion mutant and displayed hypersensitivity under low-carbon conditions. Accordingly, Van facilitated the inhibition of ICL and MLS activities in vitro. Molecular docking analyses revealed the in-silico binding affinity of Van with Icl1p and Mls1p. Those analyses were also confirmative of the binding of Van to the active sites of both proteins with better binding energy in comparison to their known inhibitors. Furthermore, Van led to the attenuation of such virulence traits as morphogenesis, biofilm formation, and cell adherence. Finally, the antifungal efficacy of Van was demonstrated by the enhanced survival of C. elegans with Candida infection. The results also confirmed negligible hemolytic activity on erythrocytes. CONCLUSION: As the findings of the present study indicated, Van is a persuasive natural compound that warrants further attention to exploit its anticandidal potential.

Frequency of risk factors, vaccination status and outcome of tetanus in children at the Children's Hospital Lahore.

OBJECTIVE: To determine the frequency of risk factors, vaccination status and outcome of tetanus in children beyond neonatal age at a tertiary care centre. METHODS: The prospective observational study was conducted at The Children's Hospital, Lahore, Pakistan, from January 2012 to December 2014, and comprised children aged between 1 month and 15 years of either gender admitted with diagnosis of tetanus. Variables recorded included age, gender, vaccination status in terms of number of diphtheria, tetanus and pertussis vaccine doses received per routine infant immunisation and booster doses of tetanus toxoid, risk factors as trauma, ear discharge, ear prick and duration of hospitalisation and outcome. Data was analysed using SPSS 16. RESULTS: Of the 74 patients, there were 47(63.5%) males and 27(36.5%) females. Overall, the mean age was 6.56+3.15 years 50(67%) were unvaccinated, none (0%) had received booster dose and posttrauma immune prophylaxis. Besides, trauma was the most common risk factor in 33(44.6%) cases followed by ear discharge 15 (20.3%) and ear/nose prick 2(2.7%), while the risk factor was unknown in 24(32.4%) cases. Mean duration of hospitalisation was 14.35±11.65. Mortality rate 16(21.6%) was significantly associated with shorter duration of stay (p<0.001). Mortality was high among unvaccinated children compared to vaccinated children (p=0.01). CONCLUSIONS: Vaccination coverage was found to be inadequate and post-trauma immune prophylaxis had been ignored..

Hearing impairment after acute bacterial meningitis in children.

OBJECTIVE: To determine the incidence of hearing loss after acute episode of meningitis in children. METHODS: A descriptive study carried out in the Department of Pediatric Medicine of The Children's Hospital Lahore, Pakistan from January 2014 to July 2016. A total of 175 children one month to 13 years of age admitted with diagnosis of meningitis were included. Complete blood count, CSF cytology, biochemistry and culture sensitivity were sent. CT scan brain was done if required. Hearing assessment was done two weeks after admission using otoacoustic emissions in the patients having normal tympanogram. Hearing impairment was classified as sensorineural if otoacoustic emissions were absent while tympanometry was normal. RESULTS: Of 175 children, 58% were males and 42% were females. Mean age was 2.1 years. Orientation as assessed by Glasgow comma scale (GCS) was normal in 63% while 5% had GCS<8 and 32% had GCS between 8 and 15. Signs of meningeal irritation were seen in 58% while focal signs only in 4%. In 15 % cases CT scan was done, out of which 73% showed abnormal findings. Otoacoustic emissions were absent in 22% of cases. Risk factors of hearing deficit were stay duration of more than 10 days (p=0.04), low GCS at presentation (p=0.009) and meningitis with complications (p=0.008). CONCLUSION: The frequency of hearing loss is 22% following acute episode of meningitis which necessitates the need for implementation of screening assessment after meningitis in Pakistan. Prolonged stay, low GCS and complicated meningitis are risk factors for hearing impairment.

Adherence to asthma treatment and their association with asthma control in children.

OBJECTIVE: To assess the degree of medication adherence among asthma patients and association of asthma control level with the degree of adherence. METHODS: This descriptive cross-sectional study was conducted at The Children's Hospital and The Institute of Child Health, Lahore, Pakistan, from January to December 2015, and comprised persistent asthma patients. Medication adherence in these paediatric subjects was assessed by using Morisky medication adherence assessment questionnaire. Children were categorised using Global Initiative for Asthma guidelines as having well-controlled, partially-controlled or uncontrolled asthma. Data was analysed using SPSS 16. RESULTS: Out of 310 subjects, 202(65%) were male and 108(34.83%) were female. The overall mean age was 8.9±3.5 years. Of the total, 66(21.3%) had well-controlled asthma, 71(22.9%) partially-controlled and 173(55.8%) uncontrolled. Low adherence was found in 138(44.5%) subjects, medium adherence in 71(22.9%), and high adherence in 101(32.6%). High adherence was significantly associated with well-controlled asthma (p<0.05). CONCLUSIONS: Adherence with medication regimen was found to be necessary for obtaining maximum therapeutic benefits in children with asthma.

A Rare Case of Kikuchi-Fujimoto Disease Associated with Systemic Lupus Erythematosus.

Kikuchi-Fujimoto Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a self-remitting, immune-mediated rare disorder having unique histopathological characteristics which is commonly seen in young Asian females, but can occur in all ethnicities. There is a strong association between KFD and Systemic Lupus Erythematosus (SLE). We present a case of a young Pakistani boy who presented with cervical lymphadenopathy, fever, blackish discoloration of finger tips, and Raynaud's phenomenon. His lymph node biopsy was suggestive of KFD. The American Rheumatology Association diagnostic criteria were not met as no other features of SLE were present. His autoimmune workup including Anti-Nuclear Antibodies (ANA) and Anti-Double Stranded DNA (Anti-Ds DNA) antibodies were positive and supported the diagnosis of SLE. He improved clinically with steroid therapy and nifedipine with resolution of symptoms.

Acute bacterial meningitis in children presenting to The Children's Hospital Lahore before and after pneumococcal vaccine in Pakistan National Immunization Program; A comparison.

OBJECTIVE: To describe bacteriological profile, morbidity and mortality of acute bacterial meningitis (ABM) in children and to compare these parameters before and after the introduction of Pneumococcal vaccine in Pakistan National Immunization Program. METHODS: The present descriptive study was conducted at the Department of Paediatric Medicine of The Children's Hospital Lahore from January 2012 to December 2015. A total of 503 children one month to five years of age admitted with diagnosis of meningitis were included. Complete blood count, CSF cytology, biochemistry, culture sensitivity and blood culture sensitivity were performed. RESULTS: Frequency of meningitis decreased by 50% in 2013-2015 (199 [2012] vs 304 [2013-2015). Most children in both groups were under one year of age. More neurological complications were seen in the group 2, 20% vs 17%. CSF culture positivity decreased from 12% to 6.6%. Streptococcus pneumoniae isolation decreased from 5 (2.5%) in 2012 to 4 (1.3%) in 2013-2015. Refusal to take feed (p=0.002), impaired sensorium (p=<0.001), severe malnutrition (p=0.001), prolonged duration of symptoms (p=<0.001) and incomplete vaccination status (0.005) were associated with mortality. Mortality rate decreased from 20 (10%) in 2012 to 17 (5.6%) in 2013-2015 but more children developed neurological sequelae 2.7% versus 1%. CONCLUSION: Acute bacterial meningitis mostly affected children <1 year. Frequency of Streptococcus pneumoniae and mortality of meningitis decreased significantly after PCV but more neurological complications developed in those children who were unvaccinated in 2013-2015 compared to 2012.

Correlation between maternal and childhood VitB12, folic acid and ferritin levels.

OBJECTIVE: To determine the correlation between serum folic acid, vitamin B12 and ferritin of mother and child and to study various neonatal risk factors as a cause of anemia in children. METHODS: One hundred eighty children two months to two years of age admitted in the department of Pediatric Medicine of The Children's Hospital and The Institute of Child Health Lahore from January 2013 to January 2015 with common medical conditions having anemia were included. Complete blood count (CBC), serum ferritin level, folic acid and Vitamin (Vit) B12 level were sent of children and their mothers. Data was analyzed using SPSS version 20. RESULTS: Out of 180 children with anemia, 66.7% were males. Mean age of children was 7.3months. Fifty-five percent children were malnourished according to z scoring. The mean Hemoglobin (Hb) of children was 8 g/dl. Only 4% children had low ferritin level while 60% had low folic acid and 45% had decreased VitB12. There was significant correlation between Hb of mother and child (p =0.02), Vit B12 deficiency (p=0.008) and iron deficiency (p<0.001). Premature children had lower folic acid levels (p =0.02), while prematurity, IUGR, previous admission and history of sepsis showed no association with anemia in our study. Both breast-feeding and top feeding showed significant association with anemia with p-value of 0.042 and 0.003 respectively while dilution showed no impact on anemia. CONCLUSION: Maternal anemia has a significant impact on child's hemoglobin. As compared to previous concept of increased iron deficiency in children we found increased occurrence of folic acid and VitB12 deficiency in children and their mothers.

Childhood Acute Bacterial Meningitis: Clinical Spectrum, Bacteriological Profile and Outcome.

OBJECTIVE: To determine the disease pattern, etiological agents and outcome of childhood acute bacterial meningitis. STUDY DESIGN: Adescriptive study. PLACE AND DURATION OF STUDY: Department of Paediatric Medicine, The Children's Hospital, Lahore, from January to December 2012. METHODOLOGY: Atotal of 199 children between the ages of 1 month and 5 years, admitted with the diagnosis of meningitis on the basis of clinical findings and positive cerebrospinal fluid (CSF), were included. In all patients, complete blood count (CBC), CSF culture sensitivity, and blood culture sensitivity were performed. Data was analysed using SPSS version 20. RESULTS: Out of 199 children, 127 (63.8%) were males with M:F ratio of 1.7:1. Mean age was 11.33 ±12 months. Maximum numbers of children were < 1 year of age, 136 (68.3%). Only 90 (45.2%) children were fully vaccinated according to Expanded Program of Immunisation (EPI) schedule. Presentations with refusal to take feed (p=0.008) and with impaired conscious state were independent predictors of death (p=0.002). Complications were noted in 34 (17%) and were significantly associated with severe malnutrition (p=0.006) and altered conscious level at presentation (p < 0.001). The common pathogens identified on CSF culture were coagulase negative staphylococci (CoNS) in 11 (5.5%) and streptococcus pneumoniaein 5 (2.5%). Overall mortality was 10.1%. The commonest pathogen isolated from children who died was streptococcus pneumoniae(p=0.039). CONCLUSION: Acute bacterial meningitis mostly affected children under the age of 1 year. CSF culture revealed both Grampositive and Gram-negative bacteria. The most common pathogen in children who died was streptococcus pneumoniae.