Immunohistochemical study of the local inflammatory response to chlamydial ocular infection

Immunohistochemical staining of conjunctival biopsies from cynomolgus monkeys (Macaca fascicularis) was performed after they received a single primary ocular infection, a single secondary challenge infection, or repeated ocular inoculations with Chlamydia trachomatis. T cells of the suppressor/cytotoxic (OKT8F) phenotype predominated regardless of the infection protocol, and perifollicular T lymphocytes of both the suppressor/cytotoxic and helper (OKT4A) phenotypes appeared in large numbers during the peak inflammatory reaction. In repeatedly inoculated monkeys, T cells and follicles persisted until cessation of reinfection. IgM-bearing B lymphocytes comprised the majority of cells within follicles, with smaller numbers of IgG- or IgA-positive B cells. The major difference in the response to the various infection protocols was the increased number and persistence of follicles with repeated reinoculation. The finding of large numbers of T-suppressor/cytotoxic and T-helper cells in the infected conjunctiva supports a role for cell-mediated immunity in the local response to C. trachomatis ocular infection.     

Molecular survey of ITS1 spacer and Rickettsia infection in human flea,Pulex irritans

Parasitology Research - The human flea is an important ectoparasite causing serious public health problems worldwide. Planning and monitoring the control programs against this vector require the...     

Oral Nitrate Reductase Activity and Erosive Gastro-esophageal Reflux Disease: A Nitrate Hypothesis for GERD Pathogenesis

Background  

Despite the rich literature on GERD, its cause and reason for increased prevalence remain obscure. Currently accepted mechanisms leave many questions unanswered. Nitrite chemistry at the GEJ is well described for carcinogenesis. Recent epidemiological and animal data have linked nitrates to GERD. “Nitrate reductase” of oral bacteria converts nitrates to nitrites. We hypothesized that nitrate reductase activity is higher in patients with erosive GERD, delivering more nitrite at the gastroesophageal-junction for a given nitrate intake.     

A double-blind, placebo controlled, randomized trial of riluzole as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia

Rationale

Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies.

Objectives

We aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties, as an adjunct to risperidone in improving negative symptoms of schizophrenia.

Methods

In this randomized double-blind placebo-controlled parallel-group study, 50 patients with chronic schizophrenia and a score of ≥20 on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. Participants were equally randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The primary outcome of this study was the difference in the decrease of PANSS negative subscale score from baseline to the study endpoint between the two groups.

Results

By the study endpoint, riluzole-treated patients showed significantly greater improvement in the negative symptoms (P?<?0.001) as well as the PANSS total and general psychopathology subscale scores (P?=?0.001 and P?<?0.001; respectively) compared to the placebo group. Treatment group was the only significant predictor of changes in negative symptom in this trial (β?=??0.56, P?<?0.001). No significant difference was observed between two groups in the frequency of side effects.

Conclusion

These preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted.

Clinical trial registry name and registration number

Iranian registry of clinical trials www.irct.ir, IRCT201107281556N26     

Intracellular Ca2+ regulates amphetamine-induced dopamine efflux and currents mediated by the human dopamine transporter

Although it is clear that amphetamine-induced dopamine (DA) release mediated by the dopamine transporter (DAT) is integral to the behavioral actions of this psychostimulant, the mechanism of this release is not clear. In this study, we explored the requirement for intracellular Ca(2+) in amphetamine-induced DA efflux and currents mediated by the human DAT. The patch-clamp technique in the whole-cell configuration was used on Na(+) and DA-preloaded human embryonic kidney 293 cells stably transfected with the human DAT (hDAT cells). Chelation of intracellular Ca(2+) by inclusion of 50 microM BAPTA in the whole-cell pipette reduced the voltage-dependent amphetamine-induced hDAT current, with the greatest effect seen at positive voltages. Likewise, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) reduced amphetamine-induced DA efflux as measured by amperometry. Furthermore, preincubation of the cells with 50 microM BAPTA acetoxy methyl ester (AM) or thapsigargin also blocked amphetamine-induced release of preloaded N-methyl-4-[(3)H]phenylpyridinium from superfused hDAT cells. BAPTA-AM also reduced DA release from striatal synaptosomes. Amphetamine also led to an increase in intracellular Ca(2+) that was blocked by prior treatment with 5 microM thapsigargin or 10 microM cocaine. These studies demonstrate that amphetamine-induced DAT-mediated currents and substrate efflux require internal Ca(2+) and that amphetamine can stimulate dopamine efflux by regulating cytoplasmic Ca(2+) levels through its interaction with DAT.     

Methamphetamine‐induced enhancement of hippocampal long‐term potentiation is modulated by NMDA and GABA receptors in the shell–accumbens

Addictive drugs modulate synaptic transmission in the meso‐corticolimbic system by hijacking normal adaptive forms of experience‐dependent synaptic plasticity. Psychostimulants such as METH have been shown to affect hippocampal synaptic plasticity, albeit with a less understood synaptic mechanism. METH is one of the most addictive drugs that elicit long‐term alterations in the synaptic plasticity in brain areas involved in reinforcement learning and reward processing. Dopamine transporter (DAT) is one of the main targets of METH. As a substrate for DAT, METH decreases dopamine uptake and increases dopamine efflux via the transporter in the target brain regions such as nucleus accumbens (NAc) and hippocampus. Due to cross talk between NAc and hippocampus, stimulation of NAc has been shown to alter hippocampal plasticity. In this study, we tested the hypothesis that manipulation of glutamatergic and GABA‐ergic systems in the shell‐NAc modulates METH‐induced enhancement of long term potentiation (LTP) in the hippocampus. Rats treated with METH (four injections of 5 mg/kg) exhibited enhanced LTP as compared to saline‐treated animals. Intra‐NAc infusion of muscimol (GABA receptor agonist) decreased METH‐induced enhancement of dentate gyrus (DG)‐LTP, while infusion of AP5 (NMDA receptor antagonist) prevented METH‐induced enhancement of LTP. These data support the interpretation that reducing NAc activity can ameliorate METH‐induced hippocampal LTP through a hippocampus‐NAc‐VTA circuit loop. Synapse 70:325–335, 2016 . © 2016 Wiley Periodicals, Inc.     

Systemic and local reactions of bee venom immunotherapy in Iran

Severe allergic reactions during specific immunotherapy may occur in the treatment of hymenoptera sting allergy. The objective of the present study was to examine the characteristics of allergic reactions during specific immunotherapy in patients with allergy towards hymenoptera venom in the Iranian population. A prospective study was performed using the clinical reports of 27 patients with anaphylaxis to bee venom (Apis melifera, Geupes vespula and Geupes Polites). Ten patients treated with Cluster protocol during 2002 and 2006 After diagnosis of hymenoptera sting allergy according to history and intradermal tests, the patient were treated with Cluster protocol immunotherapy. The protocol lasted 6 weeks with an increase in the concentration of venom from 0.01 microg/ml to 100 microg/ml. None of the patient received premedication. All patients with hymenoptera venom allergy received 120 injections. Anaphylactic reactions were classified according to the Mueller-classification. The frequencies of systemic reactions during Cluster protocol were 8.33% and 5% for yellow jacket and honey bee venom respectively. No patient experienced severe systemic reaction. Cluster protocol for hymenoptera immunotherapy is a reliable method for the treatment of anaphylactic reactions to bee venom. It is safe with low cost and do not need hospitalization.     

Goblet cell density and vascularization during conjunctival transdifferentiation

After debridement of the entire corneal epithelium with n-heptanol, two groups of rabbit corneas were segregated according to the extent of corneal neovascularization. Using a new topographic goblet-cell counting method and routine histology, the authors have reexamined the process of conjunctival transdifferentiation and compared the changes of goblet-cell density and morphology between nonvascularized and vascularized groups for a follow-up period of 167 days. Analysis of the total goblet-cell density disclosed that no goblet cells appeared on the corneal surface during the entire period of reepithelialization. After that, two phases were identified with respect to goblet-cell density: phase I (day 0-17) and phase II (after day 17). In phase I, both groups had a similar surge of goblet cells, with the peak occurring between days 7 and 11, suggesting little correlation with vascularization. Morphologic studies indicated the presence of a prominent centripetal cellular migration. In phase II, the nonvascularized group showed a rapid decline in goblet-cell density, and as a result the morphologic transdifferentiation into a cornea-like epithelium was completed on day 43. The changes of goblet cells to a smaller size and the presence of a more acidic mucin in the centrifugal receding zone, suggested that transdifferentiation on nonvascularized corneas is a process involving changes of cellular differentiation. In contrast, the vascularized group maintained a high plateau of goblet-cell density and an epithelium with conjunctival characteristics until day 167. This result disclosed that retardation of conjunctival transdifferentiation by corneal vascularization was in phase II. The possible role of vascularization in the modulation of conjunctival transdifferentiation is discussed.