Juvenile angiofibroma: review of a case series and role of embolization

Here 15 cases of advanced Juvenile angiofibroma are presented. Advantages of wide tumour exposure and preoperative embolization are discussed.     

Rhinocerebral invasive aspergillosis

Here we present 10 cases of rhinocerebral aspergillosis. In this study we included only invasive type of cases. In 4 of these disease had extended into the brain parenchyma and in remaining cases diseases had extended intracranially but dura was not invaded. Details about the operative procedure and followup is presented. Till date only 3 of these cases are surviving.     

Influence of copy number on the expression levels of pandemic influenza hemagglutinin recombinant protein in methylotrophic yeast Pichia pastoris

The hemagglutinin (HA) gene of novel Swine Origin Influenza A/California/04/2009 (H1N1) was engineered for expression in Pichia pastoris as a soluble secreted protein. The full length HA-synthetic gene having ?? secretory tag under the control of AOX1 promoter was integrated into P. pastoris genome through homologous recombination. The resultant Pichia clones having single and multiple copy integrants of the expression cassettes were screened for the expression of full length HA protein in the culture supernatant. In order to completely exploit the expression potential of the P. pastoris expression system, a systematic investigation on the influence of gene copy number on the expression of the recombinant protein was made. A panel of Pichia clones carrying increasing copies of the heterologous gene was selected based on Geneticin resistance and SYBR green-based quantitative real-time PCR approach. Using these strategies, recombinant Pichia transformants carrying up to a maximum of four to six copies of the transgene were identified. After optimising the expression conditions for shaker flask culture, the resultant clones demonstrated that the increase in copy number results in a proportional elevation in the expression level of H1N1HA recombinant protein. Our findings clearly suggest that the gene dosage effect play a vital role in high level expression of the pandemic Influenza HA protein in yeast system.     

RKIP regulates CCL5 expression to inhibit breast cancer invasion and metastasis by controlling macrophage infiltration

Accumulating evidence suggests that presence of macrophages in the tumor microenvironment add to the invasive and tumor-promoting hallmarks of cancer cells by secreting angiogenic and growth factors. RKIP is a known metastasis suppressor and interferes with several steps of metastasis. However, the mechanistic underpinnings of its function as a broad metastasis suppressor remain poorly understood. Here, we establish a novel pathway for RKIP regulation of metastasis inhibition through the negative regulation of RANTES/CCL5 thereby limiting tumor macrophage infiltration and inhibition of angiogenesis. Using a combination of loss- and gain-of-function approaches, we show that RKIP hinders breast cancer cell invasion by inhibiting expression of the CC chemokine CCL5 in vitro. We also show that the expression levels of RKIP and CCL5 are inversely correlated among clinical human breast cancer samples. Using a mouse allograft breast cancer transplantation model, we highlight that ectopic expression of RKIP significantly decreases tumor vasculature, macrophage infiltration and lung metastases. Mechanistically, we demonstrate that the inhibition of the CCL5 expression is the cause of the observed effects resulting from RKIP expression. Taken together, our results underscore the significance of RKIP as important negative regulator of tumor microenvironment.     

Vitrectomy with Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment following Acute Retinal Necrosis: Clinical Outcomes and Prognostic Factors

Purpose: The purpose of the study is to report the prognostic factors and outcomes of vitrectomy (PPV) with silicone oil tamponade in rhegmatogenous retinal detachment (RRD) secondary to acute retinal necrosis (ARN).

Methods: This retrospective, non-randomized, interventional comparative study included 38 eyes of 38 patients. All cases underwent PPV with silicone oil tamponade. The main outcome measure was improvement of final visual acuity relative to the presenting visual acuity and factors affecting the same Group A included eyes with favorable vision of 20/400 or better and Group B included the others.

Results: Group A included 16 eyes (42.10%), group B included 22 eyes (57.89%). In Group A 2 eyes out of 16 (12.5%) and in Group B 12 eyes out of 22 (54.54%) had RRD at presentation (p = 0.02, 95% CI for the difference 7.88–65.78%). The time interval between first presentation and development of RRD in Group A was 30.94 ± 38.8 days (median 30 days) whereas that in Group B was 10.81 ± 11.73 days (median 8 days) (p = 0.02). The odds of visual improvement post-vitrectomy when RRD occurred later was 8.4 (p = 0.01, 95% CI 1.53–46.1). The usage of systemic steroids (odds 5.2, p = 0.03, 95% CI 1.14–23.54) and oral valacyclovir (odds 4.33, p = 0.04, 95% CI 1.05–17.84) were associated with odds favoring a good visual outcome. Recurrent RRD was noted in 3/16 eyes (18.75%) in Group A and 13/22 eyes (59.09%) in Group B (p = 0.03).

Conclusion: Delayed occurrence of RRD after ARN is a good prognostic factor. Usage of systemic steroids and oral valacylocvir are associated with a favorable visual outcome when started before the onset of RRD.     

Incidence of anticardiolipin antibodies and lupus anticoagulant factor among women experiencing unexplained recurrent abortion and intrauterine fetal death

The aim of this research study was to estimate anticardiolipin (IgG & IgM) antibodies (aCL) and lupus anticoagulant (LA) factor in patients of recurrent unexplained pregnancy loss and intrauterine fetal deaths (IUFD). 82 women were selected for this study by virtue of having more than two consecutive unexplained pregnancy losses in their first trimester and were referred by the department of Obstetrics and Gynecology, King Saud Medical City Hospital, Riyadh, KSA. All patients had gone through a standardized investigation sequence. Lupus anticoagulants and Anticardiolipin antibodies (IgM and IgG) were detected in the serum by the enzyme linked immunosorbent assay method. To check the significance of aCL and LA, two-tailed t-test was done. Non parametric data was calculated either by Chi-Square test or Fischer exact test when relevant. Total 82 females grouped as 52 cases of recurrent (≥ 2) mainly first and second trimester miscarriage and 30 cases of recurrent (≥ 2) late intrauterine fetal death. Lupus anticoagulants was observed in twenty one (21) cases (25.6%) while anticardiolipin antibodies IgM and or IgG positive cases were estimated in forty four (44) cases (53.65%). The prevalence of APS in both studied group was thirty five (35) cases (42.68%). Antiphospholipid antibodies are calculated as the most important reason for recurrent abortion. The patients with unexplained recurrent pregnancy loss must be advised to go for a screening test for all this aPL antibodies.     

Approaches for CNS delivery of drugs – nose to brain targeting of antiretroviral agents as a potential attempt for complete elimination of major reservoir site of HIV to aid AIDS treatment

Introduction: Human immune-deficiency virus (HIV) infection causing acquired immune-deficiency syndrome (AIDS) is one of the most life-threatening infections. The central nervous system (CNS) is reported to be the most important HIV reservoir site where the antiretroviral drugs are unable to reach.

Areas covered: This article includes the review about HIV infections, its pathogenesis, HIV infections in CNS, its consequences, current therapies, challenges associated with the existing therapies, approaches to overcome them, CNS delivery of drugs – barriers, transport routes, approaches for transporting drugs across the blood–brain barrier, nasal route of drug delivery, and nose to brain targeting of antiretroviral agents as a potential approach for complete cure of AIDS.

Expert opinion: Various approaches are exploited to enhance the drug delivery to the brain for various categories of drugs. However, very few have investigated on the delivery of antiretrovirals to the brain. Targeting antiretrovirals to CNS through oral/nasal routes along with oral/parenteral delivery of drug to the plasma can be a promising approach for an attempt to completely eradicate HIV reservoir and cure AIDS, after clinical trials. Further research is required to identify the exact location of the HIV reservoir in CNS and developing good animal models for evaluation of different newly developed formulations.