Natural infestation of <Emphasis Type="Italic">Pimeliaphilus joshuae</Emphasis> on scorpion species from Egypt

The main goal of this study was to study the acarine parasite, Pimeliaphilus joshuae (Prostigmata: Pterygosomatidae) on various scorpion species from Egypt to determine its prevalence, abundance and intensity in relation to host species, size and sex. A total of 95 Leiurus quinquestriatus, 98 Androctonus australis, 40 A. amoreuxi, 30 Scorpio maurus palmatus and 46 Orthochirus scrobicuosus were examined during August 2009. Prevalence and mean abundance of P. joshuae varied significantly in relation to host species, host size and sex. In L. quinquestriatus, A. australis, and A. amoreuxi, the prevalence was 76.8, 13.3, and 50.0%, whereas the mean abundance was 47.6, 6.7 and 14.3%, respectively. Prevalence and mean abundance of P. joshuae were both positively correlated with host size in L. quinquestriatus and A. australis. We conclude that P. joshuae is found in a wide range of scorpion species exhibiting a low degree of host specificity. Controlled laboratory infection experiments are required to explain why S. m. palmatus and O. scrobicuosus are not susceptible to infestation by P. joshuae.     

Distribution of matrix metalloproteinases MMP-1, MMP-2, MMP-8 and tissue inhibitor of matrix metalloproteinases-2 in nasal polyposis and chronic rhinosinusitis

Nasal polyposis (NP), a chronic inflammatory disease of the upper airway, is a subgroup of chronic rhinosinusitis (CRS). Matrix metallo-proteinases (MMPs) and their tissue inhibitors (TIMPs) are considered to play important roles in the pathogenesis of nasal polyposis. The aim of the current study was to evaluate and compare the levels of MMP-1, MMP-2, MMP-8 and TIMP-2 in NP and CRS with normal nasal mucosa by using immunohistochemistry. Twenty-five patients with NP and fifteen patients with CRS underwent endoscopic sinus surgery. Diseased mucosal samples were obtained from ethmoidal sinuses. Control nasal mucosa (n=10) was obtained from inferior nasal turbinate. Immunohistochemistry for MMP-1, MMP-2, MMP-8 and TIMP-2 was performed. The expression of MMP-1, MMP-2 and MMP-8 significantly increased in NP and CRS compared with control (p<0.05). The distribution of TIMP-2 was higher in CRS than control and NP respectively (p<0.05). MMP-1 immunoreactivity was distributed in the extracellular matrix whereas MMP-2, MMP-8 and TIMP-2 immunostaining was present in the epithelium, submucosal glands, vascular endothelium and inflammatory cells in CRS and NP. We suggest that differences in histological features between CRS and NP might be related to the expression of MMP-1, MMP-2, MMP-8 and their tissue inhibitor-2.     

The effects of chronic long-term intermittent hypobaric hypoxia on blood rheology parameters

The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on blood rheology is not completely investigated. We designed this study to determine the effect of CLTIHH on blood rheology parameters. Present study was performed in 16 male Spraque-Dawley rats that divided into CLTIHH and Control groups. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mmHg; 5 hours/day, 5 days/week, 5 weeks). The control rats stayed in the same environment as the CLTIHH rats but they breathed room air. In the blood samples aspirated from the heart, hematocrit, whole blood viscosity, plasma viscosity, plasma fibrinogen concentration, erythrocyte rigidity index and oxygen delivery index were determined. The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen concentration values in the CLTIHH group were found to be higher than those of the control group. However, no significant difference was found in erythrocyte rigidity index and oxygen delivery index between the groups. Our results suggested that CLTIHH elevated whole blood viscosity by increasing plasma viscosity, fibrinogen concentration and hematocrit value without effecting the erythrocyte deformability. Hence, CLTIHH that may occur in intermittent high altitude exposure and some severe obstructive sleep apnea (OSA) patients may be responsible for hemorheologic changes in those subjects.     

Alterations of central hypercapnic respiratory response induced by acute central administration of serotonin re-uptake inhibitor, fluoxetine

Long-term neurochemical changes are responsible for therapeutic actions of fluoxetine. The role of increased central concentration of serotonin by inhibiting its re-uptake via fluoxetine on the central hypercapnic ventilatory response is complex and little is known. We aimed to research the effect of acute intracerebroventricular (ICV) injection of fluoxetine on hypercapnic ventilatory response in the absence of peripheral chemoreceptor impulses and the role of 5-HT2 receptors on responses. Eighteen anesthetized albino rabbits were divided as Fluoxetine and Ketanserin groups. For ICV administration of fluoxetine and ketanserin, a cannula was placed in the left lateral ventricle by the stereotaxic method. Respiratory frequency (fR), tidal volume (V(T)) and ventilation minute volume (V(E)) were recorded in both groups. ICV fluoxetine (10.12 mmol/kg) injection during normoxia caused significant increases in V(T) and V(E) (both P < 0.01) in the fluoxetine group. When the animals were switched to hypercapnia f/min, V(T) and V(E) increased significantly. The increases in percentage values in V(T) and V(E) in Fluoxetine + Hypercapnia phase were higher than those during hypercapnia alone (P < 0.01 and P < 0.05, respectively). On blocking of 5-HT2 receptors by ketanserin (0.25 mmol/kg), the ventilatory response to Fluoxetine was abolished and the degree of increases in V(T) and V(E) in the Ketanserin + Hypercapnia phase were lower than those during hypercapnia alone (P < 0.01 and P < 0.001, respectively). We concluded that acute central fluoxetine increases normoxic ventilation and also augments the stimulatory effect of hypercapnia on respiratory neuronal network by 5-HT2 receptors in the absence of peripheral chemoreceptor impulses.     

Assessment of in vivo and in vitro cytotoxic activity of hydrolysable tannin extracted from Rhizophora apiculata barks

World Journal of Microbiology and Biotechnology - Rhizophora apiculata is a common mangrove tree in Malaysia. The bark of this tree has been reported to contain a chemical constituent such as...     

Reaction of hemoglobin with HOCl: mechanism of heme destruction and free iron release

Hypochlorous acid (HOCl) is generated by myeloperoxidase using chloride and hydrogen peroxide as substrates. HOCl and its conjugate base (OCl⁻) bind to the heme moiety of hemoglobin (Hb) and generate a transient ferric species whose formation and decay kinetics indicate it can participate in protein aggregation and heme destruction along with subsequent free iron release. The oxidation of the Hb heme moiety by OCl⁻ was accompanied by marked heme destruction as judged by the decrease in and subsequent flattening of the Soret absorbance peak at 405 nm. HOCl-mediated Hb heme depletion was confirmed by HPLC analysis and in-gel heme staining. Exposure of Hb to increasing concentrations of HOCl produced a number of porphyrin degradation products resulting from oxidative cleavage of one or more of the carbon-methene bridges of the tetrapyrrole ring, as identified by their characteristic HPLC fluorescence and LC-MS. A nonreducing denaturing SDS-PAGE showed several degrees of protein aggregation. Similarly, porphyrin degradation products were identified after exposure of red blood cells to increasing concentrations of HOCl, indicating biological relevance of this finding. This work provides a direct link between Hb heme destruction and subsequent free iron accumulation, as occurs under inflammatory conditions where HOCl is formed in substantial amounts.     

Comparative efficacy and bioavailability of different praziquantel brands

This study investigates the efficacy, bioavailability and drug metabolizing enzymes mainly involved in the metabolism of the commercial brands of praziquantel (PZQ) in Egypt in comparison with the original pure powder. Mice infected with PZQ-susceptible (CD) or PZQ-insusceptible (EE2) Schistosoma mansoni isolates were divided each into seven groups, six of them received PZQ brands (Distocide, Epiquantel, Biltricide, Bilharzid, Praziquantel, and pure PZQ), while the seventh one was left as infected untreated. Seven weeks post-infection, worms were quantified and hepatic CYP450 and CYT b5 were examined. For PZQ pharmacokinetics, groups of normal mice were given the different PZQ brands and divided into subgroups, killed at 2, 5, 15, 30, 60, 90, 120,150, 180, 240 and 360 min post-dosing. Physicochemical examination revealed better dissolution rates for Biltricide, Distocide and PZQ T3A rather than Epiquantel and Bilharzid. Significant decrease in worm burden was recorded in all groups of mice regardless of the brand of PZQ used, but with better results obtained with CD isolate rather than the EE2 isolate. Biltricide and Distocide showed higher C_max and AUC_0–6h in normal mice, in addition to higher worm reduction with least inhibition of CYP450 and CYT b5 in EE2-infected mice. PZQ T3A, Bilharzid and Epiquantel showed, in addition to lower efficacy, higher K_el, lower t_1/2e, C_max and AUC_0–6h. The 32–46% reduction of their bioavailability reflected on their antischistosomal efficacy and recovery of drug metabolizing enzymes. Quality of generic PZQ should include, in addition to examining the physicochemical characteristics of the brands, biological testing including efficacy and bioavailability studies.     

Inhibition of Naja nigricolis (Reinhardt) venom protease activity by Luffa egyptiaca (Mill) and Nicotiana rustica (Linn) extracts

Luffa egyptiaca and Nicotiana rustica are used in traditional medicine to treat snakebites and were evaluated for inhibitory activities on Naja nigricolis venom protease. The aqueous and ethanolic extracts of L. egyptiaca significantly reduced the maximum velocity (Vmax) and the computed index of physiological efficiency (Kcat) of the enzyme in a dose dependent fashion. The protease activity was non-competitively inhibited by the aqueous extract of N. rustica with the Vmax significantly decreased and the K(M) remained unchanged. However, the N. rustica ethanol extract completely inhibited the protease activity. Ethyl acetate fractions partitioned from ethanol extracts of both plants were also found to completely inhibit the N. nigricolis venom protease activity at 0.1 and 0.05%. The use of these plants could be important in the treatment of snakebites.     

Chronic psychosocial stress enhances long-term depression in a subthreshold amyloid-beta rat model of Alzheimer's disease

In addition to genetic aspects, environmental factors such as stress may also play a critical role in the etiology of the late onset, sporadic Alzheimer's disease (AD). The present study examined the effect of chronic psychosocial stress in a sub-threshold Aβ (subAβ) rat model of AD on long-term depression by two techniques: electrophysiological recordings of synaptic plasticity in anesthetized rats, and immunoblot analysis of memory- and AD-related signaling molecules. Chronic psychosocial stress was induced using a rat intruder model. The subAβ rat model of AD, which was intended to represent outwardly normal individuals with a pre-disposition to AD, was induced by continuous infusion of 160 pmol/day Aβ???? via a 14-day i.c.v. osmotic pump. Results from electrophysiological recordings showed that long-term depression evoked in stress/subAβ animals was significantly enhanced compared with that in animals exposed to stress or subAβ infusion alone. Molecular analysis of various signaling molecules 1 h after induction of long-term depression revealed an increase in the levels of calcineurin and phosphorylated CaMKII in groups exposed to stress compared with other groups. The levels of the brain-derived neurotrophic factor (BDNF) were significantly decreased in stress/subAβ animals but not in stress or subAβ animals. In addition, the levels of beta-site amyloid precursor protein cleaving enzyme were markedly increased in stress/subAβ. These findings suggest that chronic stress may accelerate the impairment of synaptic plasticity and consequently cognition in individuals 'at-risk' for AD.