Neonatal Cholestasis: The Changing Etiological Spectrum in Pakistani Children.

OBJECTIVES: To determine the frequency of clinical presentation and laboratory profile in the diagnosis of the etiological spectrum of neonatal cholestasis. MATERIAL AND METHODS:  In this prospective cross-sectional study, we recruited children who presented with jaundice and direct hyperbilirubinemia with onset in the first three months of life. The study was conducted between April 2019 to March 2021 (24 months) at the Government Lady Reading Hospital of Khyber Pakhtunkhwa province in Pakistan. The diagnosis was based on history and clinical findings that included jaundice, stool color, itching, abdominal distention, and deranged liver function tests and confirmed on liver biopsy and specific diagnostic tests. Data was recorded and analyzed using SPSS version 20 (IBM Corp., Armonk, NY). RESULTS: A total of 90 children were included in the study, out of which 65.6% were male. The average age was recorded as 118.01 days + 118.1 SD. Jaundice, dark urine, and hepatomegaly were found in 85.6% of children while ophthalmologic disorder, congenital heart disease, and itching were the least common symptoms. Laboratory findings of the cholestasis patients showed high bilirubin (mean: 8.88 mg/dL), alanine transaminase (ALT) (mean: 177.48 IU/mL), aspartate transaminase (AST) (mean: 187.11 IU/mL), gamma-glutamyl transpeptidase (GGT) (mean: 187.66 IU/mL) and prolonged international normalized ratio (INR) (mean: 2.20) in majority of patients. The genetic and metabolic disorder was the leading cause found in the majority of children, which was 43.8%. CONCLUSION: The common causes of neonatal cholestasis in this study are galactosemia, idiopathic hepatitis, and biliary atresia. The common presentation includes jaundice, hepatomegaly, direct hyperbilirubinemia, raised liver enzymes, and INR.

Development, characterization and optimization of methotrexate-olive oil nano-emulsion for topical application.

The chronic inflammatory conditions like psoriasis has an increased prevalence and is linked with various associated life threatening disease conditions. The main objective of this project was to developed a methotrexate-olive loaded nano emulsion. The formulation was assessed for various parameters including Thermodynamic Stability, physico-chemically characterization, drug release kinetics and entrapment efficiency and in vitro/ in vivo skin permeation analysis. Final optimized formulation had a particle size 18.27±5.78 nm with a PDI of 0.25±0.01, whereas the average entrapment efficiency of formulation was 74.68±2.1%. The release kinetics suggested 97.72% drug release at pH 5 after 20 hrs. The FTIR data confirmed that the chemical structure of drug is retained with efficient loading into the formulation. Permeation data showed that an average of 79.23±3.6µg/cm2 of methotrexate was permeated from the nano emulsion with an average flux of 2.326±0.45µg/cm2/h after 24 hrs. Finally in vivo studies on rabbit skin confirmed that the structural changes of intercellular lipid layers in the stratum corneum are not responsible for enhanced skin permeation of methotrexate loaded nano emulsion. It was concluded that olive oil based MTX-NE is suitable for topical application and can be used for management of psoriasis.

Pharmacokinetic evaluation of quetiapine fumarate controlled release hybrid hydrogel: a healthier treatment of schizophrenia.

The current study aimed to rationally develop and characterize pH-sensitive controlled release hydrogels by graft polymerization of gelatin (Gel) and hydroxypropyl methyl cellulose (HPMC) in the presence of glutaraldehyde (GA) using quetiapine fumarate for the treatment of schizophrenia. The prepared hydrogels discs were subjected to various physicochemical studies including: swelling, diffusion, porosity, sol-gel analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Three different pH values (1.2, 6.8 and 7.4) were used to determine shape, transition, and controlled release behavior of prepared hydrogels. Various kinetic models including zero order, first order, Higuchi model and Power Law equation were applied on drug release data. The optimized hydrogels were subjected to in vivo studies using albino rabbits. Swelling and release results were found to be insignificant (p < .05) evidencing that there was no significant difference in swelling and drug release rate of hydrogels in different pH mediums. Swelling, porosity, gel-fraction, and drug released (%) were found to be dependent on concentrations of Gel, HPMC, and GA. Kinetic models revealed that QTP-F release followed non-Fickian diffusion. In-vivo studies contributed significantly higher plasma QTP-F concentration (Cmax), time for maximum plasma concentration (Tmax), area under the curve (AUC0-inf) and half-life (t1/2) as 18.32 ± 0.50 µg/ml, 8.00 ± 0.01 hrs, 6021.2 ± 5.09 µg.hrs/ml and 10.06 ± 0.43 hrs, respectively, for test-hydrogels when compared to reference market brand (Qusel® 200 mg, Hilton Pharma, Karachi, Pakistan) QTP-F tablets. It might be concluded that QTP-F loaded pH-sensitive hydrogels were developed successfully with reduced dosing frequency for schizophrenia.

Effect of organo and inorganic lithium salt on human blood plasma glutathione- A comparative study.

Investigation of toxicological effect of various metals is the field of interest for toxicological scientists since four to five decades and especially the toxicological effect of those drugs containing metals and there use is common because there is no other choice except to use these metal containing drugs. Inorganic as well as organic salts of lithium are commonly used in prophylaxis and treatments of many psychiatric disorders. The aim of the present study was to see the difference between the effect of organic and inorganic salt of lithium commonly used in psychiatric disorders on the GSH of human blood plasma. It is the scientific fact that ionic dissociation of organic and inorganic salts of any metal is always quite different hence to prove this fact, the effect of lithium citrate (organic salt of lithium) and lithium carbonate (inorganic salt of lithium) was investigated on human blood plasma GSH to find the difference between the effect of two. Ellman's method was used for the quantification of glutathione contents in plasma. It was found that lithium citrate decrease plasma GSH contents less than lithium carbonate indicating that organic salts of lithium are safe than inorganic salts of lithium when are used in psychiatric disorders. Further to analyze the effect of organic and inorganic salt of lithium on blood plasma GSH with the increase in incubation time was also evaluated and was found that both concentration and time dependent effect of organic salt of lithium shows that this salt has decreased plasma GSH contents of human blood less than inorganic salt of lithium either by promoting oxidation of GSH into GSSG or by lithium glutathione complex formation. These results suggest the physicians that the use of organic lithium salts is much safer than inorganic salts of lithium in terms of depletion of blood plasma GSH contents.

Depletion of GSH in human blood plasma and cytosolic fraction during cadmium toxicity is temperature and pH dependent.

Toxicities of heavy metals is a burning issue and a topic of interest among the toxicologists throughout the world. Metals are always in use of man since long but in recent years the use of cadmium has increased in the form of various cadmium compounds such as cadmium compounds as stabilizers in plastic pipe industries and in the preparations of different alloys etc. Cadmium is even used in phosphate fertilizers and thus comes directly or indirectly in contact with human eatables like crops, vegetables and fruits. Once it is absorbed it affects almost all the organs and systems of human body especially blood components and kidneys. Always the chemical reactions of different chemicals are dependent on some influential factors, among these factors the effect of pH and temperature of the media in which these chemicals interact with each other are very much important. Keeping in view this fact we have evaluated the effect of cadmium nitrate tetra hydrate on GSH of human plasma and cytosolic fraction. Estimation of thiol was done by Ellman's modified method and was found that the interaction of cadmium nitrate tetra hydrate and GSH of these blood components was more at a pH and temperature, which were near to physiological pH and temperature of human body. This fact was proved as the estimated thiol concentration left after the interaction of cadmium nitrate tetra hydrate and thiol of these blood components was minimum at pH and temperature near to human blood pH and temperature. We concluded that the possible reason for depletion of GSH of these blood components was conversion of GSH into Cd(SG) (2) and/or GSSG formation.

Cadmium-glutathione complex formation in human t-cell and b-cell lymphocytes after their incubation with organo-cadmium diacetate.

Cadmium intake is associated with oxidative stress that causes depletion of intracellular as well as extra cellular reduced glutathione. There is strong evidence indicating that reactive oxygen species and reactive nitrogen species generated in the presence of cadmium could be responsible for its toxic effects in many cells and tissues. Depletion of reduced glutathione in various cells, especially in T and B-lymphocytes, causes extreme damage to the antioxidant defense system of body. The aim of this research work was to investigate the metabolic changes that occur in T and B lymphocytes after their incubation with organ cadmium diacetate by using Ellman's spectrophotometric method of thiol quantification. The results of the present study indicate that cadmium depleted T and B lymphocytes GSH to a harmful extent. It is proposed that this depletion is due to the bivalent cadmium glutathione complex formation, oxidation of reduced glutathione (GSH) to its oxidized form, or both.