Molecular mechanisms underlying occult hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section.     

Subcutaneous administration of alemtuzumab in patients with highly active multiple sclerosis

Alemtuzumab is an anti-CD52 monoclonal antibody with remarkable efficacy in relapsing multiple sclerosis (MS). In clinical trials and off-label use in MS, alemtuzumab has been administered intravenously (IV). Alemtuzumab is approved for chronic lymphoid leukemia as IV. Oncology guidelines recommend alemtuzumab subcutaneous (SC) over IV. There is no report of alemtuzumab SC in MS. We report two patients with highly active relapsing MS who were treated with SC alemtuzumab, had significant improvement and tolerated SC alemtuzumab well without the typical infusion-associated adverse events. SC alemtuzumab in MS warrants further studies as this may enhance patient convenience and minimize infusion-associated adverse events.     

Possible relationship among socio-economic determinants,knowledge and practices on lymphatic filariasis and implication for disease elimination in India

Objective  

To assess the socio-economic determinants, knowledge and practices on lymphatic filariasis in India and discuss the implications for elimination.     

Immunological characterization of recombinant Wuchereria bancrofti cuticular collagen(COL-4)as putative vaccine candidate for human lymphatic filariasis

Objective:To elucidate immunoprophylactic potential of recombinant Wuchereria bancrofti(W.bancrofti)cuticular collagen(COL-4)in BALB/c mice and filarial clinical samples.Methods:col-4 gene was PCR amplified from W.bancrofti L3 cDNA library and cloned in pRSET B vector.Recombinant COL-4 was over expressed in salt inducible system and was purified by nickel afiinity chromatography.Humoral and cellular responses were measured by EUSA and peripheral blood mononuclear cells(PBMC)of various filarial clinical samples respectively using purified recombinant COL-4 antigen.Then the protective immune responses of COL-4 immunized BALB/c mice were characterized.Results:Sequence analysis of COL-4 with human host proteins reveals lack of homology.The recombinant COL-4 was found to be at 15 kDa fusion protein.The affinity purified COL-4 showed significant reactivity with putatively immune sere and in a similar fashion it demonstrated marked proliferation in PBMC samples.Immunization studies in experimental filarial host(mice)elicited significant liters with protective antibody isotype profile(IgM and IgG).Cellular immune responses were also significant in terms of splenocytes proliferation assay on mice samples.Conclusions:Our immunological findings in experimental host suggest Th2mediated immune response.Hence,we propose that W.bancrofti COL-4 could be an efficacious vaccine candidate against lymphatic filariasis.     

Evaluation der COVID-19-Impfung nach breiter Anwendung – ein Zwischenfazit für Deutschland im Juli 2022

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Seit Dezember 2020 stehen in Deutschland Impfstoffe gegen COVID-19 zur Verfügung. Zu den Hauptaufgaben des Fachgebiets...     

Effect of poly(amidoamine) (PAMAM) dendrimer on skin permeation of 5-fluorouracil

The aim of present study is to investigate the effect of poly(amidoamine) (PAMAM) dendrimer on skin permeation of 5-fluorouracil (5FU). Permeation studies were performed using excised porcine skin in a Franz diffusion cell and (14)C labeled 5FU samples were analyzed using liquid scintillation counter. Three different vehicles were used, including phosphate buffer (PB), mineral oil (MO) and isopropyl myristate (IPM). The studies were carried out by simultaneously applying the drug and dendrimer together or by pre-treating the skin with dendrimer before drug application. Simultaneous application of drug and dendrimer increased the flux of 5FU in IPM and MO, while there was no change in PB. The increased skin partitioning of dendrimer from lipophilic vehicles increased the drug solubility in skin. Pre-treatment with dendrimer increased permeability coefficient of 5FU by 4-fold in MO and 2.5-fold in IPM, while it decreased by half in PB. Skin partitioning of 5FU increased after dendrimer treatment from lipophilic vehicles. The flux increased linearly with increase in pre-treatment time. Dendrimer pre-treatment increased transepidermal water loss and decreased skin resistance. The decrease in skin resistance directly correlated to the enhancement in skin permeation of 5FU (r(2)=0.99). Overall, the study showed that dendrimer increases the skin permeation of 5FU from lipophilic vehicles mainly by altering the skin barrier.     

Discovery of antimycobacterial spiro-piperidin-4-ones: an atom economic, stereoselective synthesis, and biological intervention

An atom economic and stereoselective synthesis of several spiro-piperidin-4-ones through 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin and alpha-amino acids viz . proline, phenylglycine, and sarcosine to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones is described. These compounds were evaluated for their in vitro and in vivo activity against Mycobacterium tuberculosis H37Rv (MTB), multidrug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC(2)). Compound 4-(4-fluorophenyl)-5-phenylpyrrolo(spiro[2.3']oxindole)spiro[3.3']-1'-methyl-5'-(4-fluorophenylmethylidene)piperidin-4'-one (4e) was found to be the most active in vitro with a MIC value of 0.07 microM against MTB and was 5.1 and 67.2 times more potent than isoniazid and ciprofloxacin, respectively. In vivo, compound 4e decreased the bacterial load in lung and spleen tissues with 1.30 and 3.73-log 10 protections respectively and was considered to be promising in reducing bacterial count in lung and spleen tissues.     

Iron Oxide Nanoparticles Induces Cell Cycle-Dependent Neuronal Apoptosis in Mice

Iron oxide (Fe₂O₃) nanoparticles (NPs) with its unique magnetic and paramagnetic properties are popular in biomedical applications. Some of their neurotoxic mechanisms due to repeated administration are proven. However, we speculate that the neuronal damage might be due to apoptosis resulting from unusual cell cycle entry. Moreover, iron accumulation has been shown to be closely associated with most of the neurodegenerative disorders. Thus, in the current study, mice were orally (po) treated with the Fe₂O₃-NPs to investigate cell cycle-associated events/components and occurrence of apoptosis. A subsequent increase in oxidant levels was observed with the iron accumulation due to Fe₂O₃-NPs exposure. The accumulated β-amyloid and reduced level of cdk5 seem to aid in the cell cycle entry and forcing progression towards apoptosis. Expression of Cyclin D1 and pRb (Ser 795) indicate the cell cycle re-entry of neurons. Overexpression of RNA Pol II and PARP cleavage suggests DNA damage due to Fe₂O₃-NPs exposure. Further, hyperphosphorylation of p38 (Thr 180/Tyr 182) confirms the activation of DNA damage-dependent checkpoint. Expression patterns of pro- and anti-apoptotic markers, TUNEL and TEM indicate the occurrences of apoptosis.     

Comparison of Reverse Sural Artery Flap Healing for Traumatic Injuries Above and Below the Ankle Joint

The reverse sural artery (RSA) flap is popular among trauma surgeons to cover the distal third of the leg to the foot. However, flaps that inset in the foot seem to have a high necrosis rate. This study compared the healing of RSA flaps performed for defects proximal to the ankle versus defects distal to the ankle. Patient data were collected retrospectively between January 2005 and December 2009. Eighty-five patients with the lower leg, ankle, and traumatic foot injuries were divided into 2 groups. Group 1 (49 patients) had RSA flap cover for soft tissue and bony defect proximal and up to the ankle joint line, and group 2 (36 patients) had RSA flap cover distal to the ankle joint line. The time to healing and type of healing were compared between the groups. The demographics between the 2 groups were similar. The successful RSA flap healing rate was 65% in group 1 (32 of 49) and 42% in group 2 (15 of 36). The average time to flap healing between the groups was similar (p?=?.16). Group 1 had predominantly primary healing compared with group 2 (p?=?.03). Group 2 had a higher reoperation rate for wound necrosis, which was significant (p?=?.001). The success of the RSA flap is higher when used for proximal to ankle joint line defects. Surgeons should be aware of the chances of flap necrosis when undertaking RSA flap cover distal to the ankle joint line.