Patients on HAART often have an excess of unintegrated HIV DNA: implications for monitoring reservoirs

HIV establishes a latent reservoir early in infection that is resistant to anti-retroviral therapy and has a slow rate of decay. It is thought that the majority of HIV DNA in treated patients is integrated since unintegrated HIV DNA appears to be unstable. Thus, to monitor the HIV latent reservoir, total HIV DNA is commonly measured in PBMC from infected individuals. We investigated how often total approaches integrated HIV DNA in treated patients. To do this, we first assessed how accurate our integration assay is and determined the error in our measurements of total and integrated HIV DNA. We demonstrated an excess of total over integrated HIV DNA was present in a subset of patients, suggesting that measurements of total HIV DNA do not always correlate to the level of integration. Determining the cause of this excess and its frequency may have important implications for understanding HIV latent reservoir maintenance.     

Effect of the Total Facet Arthroplasty System after complete laminectomy-facetectomy on the biomechanics of implanted and adjacent segments

Background contextLumbar fusion is traditionally used to restore stability after wide surgical decompression for spinal stenosis. The Total Facet Arthroplasty System (TFAS) is a motion-restoring implant suggested as an alternative to rigid fixation after complete facetectomy.PurposeTo investigate the effect of TFAS on the kinematics of the implanted and adjacent lumbar segments.Study designBiomechanical in vitro study.MethodsNine human lumbar spines (L1 to sacrum) were tested in flexion-extension (+8 to ?6 Nm), lateral bending (±6 Nm), and axial rotation (±5 Nm). Flexion-extension was tested under 400 N follower preload. Specimens were tested intact, after complete L3 laminectomy with L3–L4 facetectomy, after L3–L4 pedicle screw fixation, and after L3–L4 TFAS implantation. Range of motion (ROM) was assessed in all tested directions. Neutral zone and stiffness in flexion and extension were calculated to assess quality of motion.ResultsComplete laminectomy-facetectomy increased L3–L4 ROM compared with intact in flexion-extension (8.7±2.0 degrees to 12.2±3.2 degrees, p<.05) lateral bending (9.0±2.5 degrees to 12.6±3.2 degrees, p=.09), and axial rotation (3.8±2.7 degrees to 7.8±4.5 degrees p<.05). Pedicle screw fixation decreased ROM compared with intact, resulting in 1.7±0.5 degrees flexion-extension (p<.05), 3.3±1.4 degrees lateral bending (p<.05), and 1.8±0.6 degrees axial rotation (p=.09). TFAS restored intact ROM (p>.05) resulting in 7.9±2.1 degrees flexion-extension, 10.1±3.0 degrees lateral bending, and 4.7±1.6 degrees axial rotation. Fusion significantly increased the normalized ROM at all remaining lumbar segments, whereas TFAS implantation resulted in near-normal distribution of normalized ROM at the implanted and remaining lumbar segments. Flexion and extension stiffness in the high-flexibility zone decreased after facetectomy (p<.05) and increased after simulated fusion (p<.05). TFAS restored quality of motion parameters (load-displacement curves) to intact (p>.05). The quality of motion parameters for the whole lumbar spine mimicked L3–L4 segmental results.ConclusionsTFAS restored range and quality of motion at the operated segment to intact values and restored near-normal motion at the adjacent segments.     

Submitral aneurysmorraphy with mitral valve replacement — A case report

Submitral left ventricular aneurysm is a rare complex disorder, predominently found in African population. We report a case of a 45 year male diagnosed to have a large submitral aneurysm, eroding the left circumflex artery, leading to severe mitral regurgitation, severe tricuspid regurgitation and congestive heart failure. Surgical correction comprising of submitral aneurysmorraphy with Teflon Felt, mitral valve replacement, modified DeVega’s tricuspid annuloplasty and ligation of left distal circumflex was performed successfully in this case.     

Fungus-mediated synthesis of silver nanoparticles and their activity against pathogenic fungi in combination with fluconazole

Silver nanoparticles (Ag-NPs) are known to have inhibitory and bactericidal effects. Resistance of fungal infections has emerged in recent years and is a major health problem. Here, we report the extracellular biosynthesis of Ag-NPs using a common fungus, Alternaria alternata. Also in this study, these nanoparticles were evaluated for their part in increasing the antifungal activity of fluconazole against Phoma glomerata, Phoma herbarum, Fusarium semitectum, Trichoderma sp., and Candida albicans. The antifungal activity of fluconazole was enhanced against the test fungi in the presence of Ag-NPs. Fluconazole in combination with Ag-NPs showed the maximum inhibition against C. albicans, which was confirmed from the increase in fold area of inhibition, followed by P. glomerata and Trichoderma sp., which showed less increase in the fold area, whereas no significant enhancement of activity was found against P. herbarum and F. semitectum.From the Clinical EditorThe antifungal activity of fluconazole was enhanced in presence of silver nanoparticles against the test fungi. Fluconazole in combination with Ag-NPs showed the maximum inhibition against C. albicans, followed by P. glomerata and Trichoderma sp. No significant enhancement of activity was found against P. herbarum and F. semitectum.     

Simultaneous spectrophotometric estimation of Hydrochlorothiazide, Atenolol and Losartan potassium in tablet dosage form

Two simple, accurate and reproducible spectrophotometric methods have been developed for the simultaneous estimation of Hydrochlorothiazide (Hctz), Atenolol (Atn) and Losartan potassium (Los) in combined tablet dosage forms. The first method involves determination using the simultaneous equation method, the sampling wavelengths selected are, 272.5 nm, 224 nm and 250 nm over the concentration ranges of 0.5-30 microg/ml, 1-50 microg/ ml and 1-60 microg/ml for Hctz, Atn and Los respectively. The second method is the First order derivative method, the sampling wavelengths selected for estimation of Hctz, Atn and Los are 280.5 nm, 233 nm and 244 nm with linearity in the concentration ranges of 0.5-30 microg/ ml, 1-50 microg/ml and 1-60 microg/ml respectively. The results of the analysis were validated statistically and recovery studies were carried out as per ICH guidelines.     

Extracranial meningioma of the parapharyngeal space: report of a case and review of the literature

Parapharyngeal tumours are frequently encountered in clinical practice and are often difficult to diagnose upon clinical examination due to the anatomic complexity of the region. We report a rare case of extracranial meningioma of the parapharyngeal space in a patient with no history of von Recklinghausen's disease, family history of meningioma or central neurofibromatosis (NF-2). The purpose of this report is to reiterate and emphasize the role of CT and MRI in the diagnosis of parapharyngeal masses, and to describe the characteristic radiological features of extracranial meningiomas.     

Stability-indicating HPTLC method for simultaneous determination of nateglinide and metformin hydrochloride in pharmaceutical dosage form

A stability indicating high performance thin layer chromatography (HPTLC) method was developed and validated for determination of two anti-diabetic drugs, nateglinide and metformin hydrochloride in co-formulations. Study was performed on pre-coated silica gel HPTLC plates using chloroform:ethyl acetate:acetic acid (4:6:0.1 v/v/v) as the mobile phase. A TLC scanner set at 216 nm was used for direct evaluation of the chromatograms in the reflectance/absorbance mode. Method was validated according to ICH guidelines. The correlation coefficients of calibration curves were found to be 0.996 and 0.995 in the concentration range of 200–2400 and 500–3000 ng band⁻¹ for nateglinide and metformin, respectively. The method had an accuracy of 99.72% for nateglinide and 100.08% for metformin hydrochloride. The method had the potential to determine these drugs simultaneously from dosage forms without any interference of the tablets excipients. Nateglinide and metformin hydrochloride were also subjected to acid, base, oxidation, wet, heat and photo-degradation studies. The degradation products obtained were well resolved from the pure drugs with significantly different R_f values. As the method could effectively separate the drugs from its degradation products, it can be used for stability-indicating analysis.     

Selection of replicon variants resistant to ACH-806, a novel hepatitis C virus inhibitor with no cross-resistance to NS3 protease and NS5B polymerase inhibitors

We have discovered a novel class of compounds active against hepatitis C virus (HCV), using a surrogate cellular system, HCV replicon cells. The leading compound in the series, ACH-806 (GS-9132), is a potent and specific inhibitor of HCV. The selection of resistance replicon variants against ACH-806 was performed to map the mutations conferring resistance to ACH-806 and to determine cross-resistance profiles with other classes of HCV inhibitors. Several clones emerged after the addition of ACH-806 to HCV replicon cells at frequencies and durations similar to that observed with NS3 protease inhibitors and NS5B polymerase inhibitors. Phenotypic analyses of these clones revealed that they are resistant to ACH-806 but remain sensitive to other classes of HCV inhibitors. Moreover, no significant change in the susceptibility to ACH-806 was found when the replicon cellular clones resistant to NS3 protease inhibitors and NS5B polymerase inhibitors were examined. Sequencing of the entire coding region of ACH-806-resistant replicon variants yielded several consensus mutations. Reverse genetics identified two single mutations in NS3, a cysteine-to-serine mutation at amino acid 16 and an alanine-to-valine mutation at amino acid 39, that are responsible for the resistance of the replicon variants to ACH-806. Both mutations are located at the N terminus of NS3 where extensive interactions with the central hydrophobic region of NS4A exist. These data provide evidence that ACH-806 inhibits HCV replication by a novel mechanism.