Expansion of urban cutaneous leishmaniasis into rural areas of southeastern Iran: Clinical,epidemiological and phylogenetic profiles explored using 7SL high resolution melting‐PCR analysis

Cutaneous leishmaniasis (CL) has increased remarkably in Iran and has expanded into new areas. The present study aimed to assess the emerging CL outbreak in southeastern Iran using high resolution melting‐polymerase chain reaction (HRM‐PCR) and phylogenetic analysis using the 7SL RNA gene marker. A cross‐sectional and analytical survey was conducted during a house‐to‐house census of 11,021 inhabitants in Narmashir County in southeastern Iran in 2016. The cases were detected by direct smear microscopic examination and sequencing and were characterized using the 7SL RNA gene. All age groups and sexes were equally affected. Most were single lesions (70.7%). The hands (55.2%) and face (37.9%) were the main sites of involvement. The disease was more common among illiterate persons. Sequencing and HRM‐PCR revealed that Leishmania tropica (accession no. MH632168 Qale‐Shahid) was the principal causative agent of anthroponotic CL (ACL) in new areas of expansion. This is the first emergence of ACL in rural areas of Narmashir County. Based on the molecular data, the causative parasite species confirmed to be L. tropica. Sequencing and phylogenetic analysis indicated that a single clone of the organism derived from a single source has spread into the affected villages. Construction of a main road, population movement and recent urbanization in the area are likely the major factors associated with the establishment of this new outbreak. This study was essential to enable the planning of effective therapeutic and prophylactic measures to control the disease.     

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.

     

Detection of Epstein-Barr Virus and Cytomegalovirus in Gastric Cancers in Kerman,Iran

Gastric cancer (GC) is a multifactorial disease with different factors having roles in its genesis. Helicobacter pylori and Epstein-Barr virus (EBV) are known infectious agents that could contribute. In addition, there is evidence of a relationship with cytomegalovirus (CMV). Since data on CMV prevalence in gastric cancer are limited, we here evaluated the frequency of EBV and CMV in Iranian patients. Ninety paraffin blocks of GC tissues from patients in Kerman were evaluated for the presence of EBV and CMV genomes by real-time polymerase chain reaction. EBV was detected in 10 cases (11.1%) and CMV in seven. One out of 17 female patients (5.88%) and nine out of 73 male patients (12.3%) were positive for EBV, while one out of 17 female patients (5.88%) and six out of 73 male patients (8.22%) were positive for CMV. The mean age for EBV-positive patients was 60.514.9 years and the mean age for CMV-positive patients was 67.912.3years. This study shows that the frequency of EBV-associated GC is high in Kerman. It also indicates that further studies of associations between GC and CMV are warranted, covering larger samples and populations from different areas of the world.     

Additive anticonvulsant effects of agmatine and lithium chloride on pentylenetetrazole-induced clonic seizure in mice: involvement of α₂-adrenoceptor

After 60 years, lithium is still the mainstay in the treatment of mood disorders and widely used in clinic. In addition to its mood stabilizer effects, lithium also shows some anticonvulsant properties. Similar to lithium, agmatine also plays a protective role in the CNS against seizures and has been reported to enhance the effect of different antiepileptic agents. Moreover, both agmatine and lithium have modulatory effects on α(2)-adrenoceptors. So, we designed this study: 1) to investigate whether agmatine and lithium show an additive effect against clonic seizures induced by pentylenetetrazole; 2) to assess whether this additive effect is mediated through the α(2)-adrenoceptor or not. In our study, acute administration of a single effective dose of lithium chloride (30 mg/kg, i.p.) increased the seizure threshold. Pre-treatment with low and, per se, non-effective doses of agmatine (1 and 3mg/kg) potentiated a sub-effective dose of lithium (10mg/kg). Interestingly, the anticonvulsant effects of these effective combinations of lithium and agmatine were prevented by pre-treatment with low and non-effective doses of yohimbine [α(2)-adrenoceptor antagonist] (0.1 and 0.5mg/kg). On the other hand, clonidine [α(2)-adrenoceptor agonist] augmented the anticonvulsant effect of a sub-effective combination of lithium (5mg/kg i.p.) and agmatine (1mg/kg) at relatively low doses (0.1 and 0.25mg/kg). In summary, our findings demonstrate that agmatine and lithium chloride exhibit additive anticonvulsant properties which seem to be mediated through α(2)-adrenoceptor.     

Bicistronic expression plasmid encoding allergen and anti-IgE single chain variable fragment antibody as a novel DNA vaccine for allergy therapy and prevention

Several approaches have been applied in order to alleviate the difficulties allergic patients are suffering from. Among them DNA vaccination and anti-IgE antibody have shown promising results. Herewith, a combination of both strategies is proposed to minimize IgE production while inducing high levels of blocking IgG and strong Th1 immune responses. A bicistronic expression plasmid including an internal ribosomal entry site (IRES) can express both, allergen and a single chain variable fragment (scFv) antibody against human IgE within antigen presenting cells (APCs) including B cells. Presentation of allergen derived peptides via MHC I and MHC II stimulates specific Th1 responses resulting in high levels of IFN-gamma and IgG. Anti-IgE scFv antibody binds to newly synthesized IgE molecules within B cell cytoplasm and also to free serum IgE, thereby inhibiting attachment of IgE to its receptors on basophils and mast cells. Also, IgE-anti-IgE complex functions as blocking antibody and neutralizes allergens entering the body. Additionally, anti-IgE scFv antibody binds to membrane bound IgE (mIgE) on B cells and interferes with IgE expression. Using assays, such as enzyme linked immunosorbent assay (ELISA), IgG and IgE production in response to this expression system can be evaluated. Also, rat basophil leukemia cell assay (using RBL-2H3 cells) can show the amount of functional IgE in sera as basophil mediator release is regarded as an indicator of the allergic hypersensitive reactions. The proposed approach may result in high levels of blocking IgG and low levels of IgE secretion from B cells. Additionally, it can inhibit activity of IgE in degranulation of basophils and mast cells.     

Emergent image-guided treatment of a large CSF leak to reverse "in-extremis" signs of intracranial hypotension

We report the use of an emergent, targeted fibrin spinal epidural blood patch with subarachnoid saline infusion to rapidly reverse "in-extremis" clinical and imaging signs of posterior-fossa coning brought about by acute-on-chronic intracranial hypotension, itself consequent to a cervicothoracic CSF leak. Treatment resulted in a dramatic recovery and eventual discharge with return to normal lifestyle and occupation. The clinical and imaging danger signs are reviewed; fibrin patch technique and potential pitfalls in postprocedure management are analyzed.