Serum HBsAg quantification in treatment-naïve Indian patients with chronic hepatitis B

Background and Aims

There is paucity of Indian data regarding serum HBsAg levels (qHBsAg) in treatment-naïve chronic hepatitis B (CHB). This study was done to determine correlation of qHBsAg with hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels and its ability to independently categorize subgroups of CHB.

Methods

We studied 131 treatment-naive CHB patients and initially classified them based on HBeAg status. The HBeAg-positive group was further classified into immune tolerance (IT) and immune clearance (IC) phases based on serum alanine aminotransferase. HBeAg-negative patients were classified into low replicators (LR) and HBeAg-negative chronic hepatitis (ENH) based on DNA levels. HBsAg quantification was performed using the Architect chemiluminescence system.

Results

HBeAg-positive patients had higher DNA (7.89 vs. 2.69 log₁₀?IU/mL) and higher qHBsAg (4.60 vs. 3.85 log₁₀?IU/mL) compared to the HBeAg-negative group. Good correlation between qHBsAg and DNA was seen in HBeAg-positive (ρ?=?0.6, p?<?0.001) but not in HBeAg-negative CHB (ρ?=?0.2). A qHBsAg level greater than 4.39 log₁₀?IU/mL predicted HBeAg-positive state with 81 % sensitivity and 85 % specificity. However, among HBeAg-negative CHB, qHBsAg failed to discriminate between LR and ENH.

Conclusions

A single point estimation of qHBsAg in treatment-naïve patients could predict replicative HBeAg-positive CHB, but was not helpful in defining replicative status in the HBeAg-negative CHB.     

Holographic Characterization of Protein Aggregates in the Presence of Silicone Oil and Surfactants

Characterizing protein aggregates in the presence of silicone oil is a long standing challenge for the pharmaceutical industry. Silicone oil is often used as a lubricant in devices that deliver and store therapeutic protein products and has been linked to protein aggregation, which can compromise a drug’s effectiveness or cause autoimmune responses in patients. Most traditional technologies cannot quantitatively distinguish protein aggregates and silicone oil in their native formulations for sizes less than 5 μm. We use holographic video microscopy to study protein aggregation to demonstrate its capability to quantitatively distinguish protein aggregates and silicone oil in the presence of varying amounts of the surfactants SDS and polysorbate 80 in the size range of 0.5-10 μm without the need for dilution or special sample preparation. We show that SDS denatures proteins and stabilizes silicone oil. We also show that polysorbate 80 may limit protein aggregate formation if it is added to an IgG solution before introducing silicone oil.     

Blood‐based diagnostic testing for Pompe disease: Consistency between GAA enzyme activity in dried blood spots and GAA gene sequencing results

Introduction: We have identified a large consanguineous Lebanese family with 5 individuals with severe childhood‐onset recessive sensory loss associated with deafness and variable optic atrophy. Methods: Autozygosity mapping was performed in all affected individuals, followed by whole‐exome sequencing (WES) in 2 individuals. Results: WES identified a homozygous missense mutation (c.916G>A, p.G306R) in the cerebral riboflavin transporter SLC52A2, recently shown to cause Brown‐Vialetto‐Van‐Laere syndrome (BVVLS), which is considered primarily a motor neuronopathy. Our patients have a phenotype distinct from BVVLS, characterized by severe progressive sensory loss mainly affecting vibration and proprioception that evolves to include sensorineural hearing loss in childhood, variable degrees of optic atrophy, and marked upper extremity weakness and atrophy. Treatment of 3 patients with 400 mg/day riboflavin over 3 months produced definite clinical improvement. Conclusions: Mutations in SLC52A2 result in a recognizable phenotype distinct from BVVLS. Early recognition of this disorder is critical, given its potential treatability. Muscle Nerve 50 : 775–779, 2014     

Appraisal of Laparoscopic Liver Resection in the Treatment of Liver Metastasis with Special Reference to Outcome in Colorectal Malignancies

Treatment of metastatic liver disease is at the crossroads of an evolutionary transformation with more and more reports reiterating the benefits of resectional therapy in various cancers. A quest for application of laparoscopic approaches to the management of liver metastasis has arisen due to the projected benefits of less morbidity, early recovery, and equivalent oncological outcome in selected malignancies. However, the diverse and heterogenous data on indications, operative technique, and outcome evaluation make a comparative analysis of these studies difficult. This review is an appraisal of technique and outcome of minimally invasive liver resection as reported in the current literature with special reference to treatment of metastatic colorectal cancers.     

Surgical management of hepatic arterioportal fistula in a neonate

Congenital arterioportal fistulae in the liver are rare malformations which can lead to portal hypertension. We report a hepatic arterioportal fistula in a neonate who presented with intestinal hypoperfusion. Computerised tomography angiography showed a fistulous communication between the left hepatic artery and portal vein with hypoperfusion of small and large bowel. A formal left hepatectomy was done followed by clinical improvement and reduction in portal venous pressures. The case and the literature pertaining to it are discussed.     

An evaluation of liposome-based diagnostics of pulmonary and extrapulmonary tuberculosis

ABSTRACT

Introduction: Tuberculosis (TB) is still one of the major global health threats and delayed diagnosis or misdiagnosis continues to fuel the global epidemic. The conventional diagnostic approaches have shortcomings that might hinder the process of diagnosis of the disease and ultimately affect the prognosis.

Area covered: We emphasize on the process of the synthesis of liposomes, its physicochemical properties affecting the formulation and their utilization in the field of molecular diagnostics for TB. The review also sheds a light on other nanoparticle-based molecular diagnostic approaches for TB. Despite the advent of science, we are yet to have a diagnostic tool that is simple, rapid, sensitive, and specific, and most importantly, one that enables us to demarcate patients with active tuberculosis from those with quiescent lesions, prior vaccination, or other diseases.

Expert opinion: The utility of liposomes for diagnostic purposes has been attempted so as to overcome the challenges posed by conventional diagnostic tools for TB. Through this review, we present insights into liposome formulation and selection processes, various studies that report the use of liposome-based diagnostic tools for TB, as well as the limitations associated with the same that can be improvised to make the technology more efficient.     

Persulfate-activated charcoal mixture: an efficient oxidant for the synthesis of sulfonated benzo[d][1,3]oxazines from N-(2-vinylphenyl)amides and thiols in aqueous solution

A series of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d][1,3]oxazines in good to excellent yields have directly been obtained from N-(2-vinylphenyl)amides and thiols by employing a mixture of K₂S₂O₈-activated charcoal in aqueous acetonitrile solution at 50 °C. A plausible mechanism for the reaction is reported. It reveals that the reaction follows a radical pathway and the persulfate has been the oxygen source for formation of the sulfone group in the products. It is worth mentioning that this protocol utilizes an easily accessible K₂S₂O₈-activated charcoal mixture and thiols, respectively, as an oxidant and sulfonylating precursors for the first time.

A simple method for the synthesis of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d][1,3]oxazines using an easily accessible K₂S₂O₈-activated charcoal mixture and thiols, respectively, as an oxidant and sulfonylating precursors has been described.