Satureja khuzestanica attenuates apoptosis in hyperglycemic PC12 cells and spinal cord of diabetic rats

Several studies have indicated the involvement of oxidative stress and high glucose-induced cell death in the development of diabetic neuropathy. Satureja khuzestanica has been recommended in the literature as a remedy for the treatment of diabetes, and also contains antioxidant agents. Here, we investigated the possible neuroprotective effects of Satureja khuzestanica extract (SKE) on in vitro and in vivo models of diabetic neuropathy pain. High-glucose-induced damage to pheochromocytoma (PC12) cells and in streptozotocin-induced diabetic rats was studied. Tail-flick and rotarod treadmill tests were used to access nociceptive threshold and motor coordination, respectively. Cell viability was determined by MTT assay. Activated caspase 3 and Bax/Bcl-2 ratio??biochemical markers of apoptosis??were evaluated using immunoblotting. We found that elevating the glucose in the medium (to 4× normal) increased cell toxicity and caspase-3 activation in PC12 cells. Incubation with SKE (200 and 250???g/ml) decreased cell damage. Furthermore, the diabetic rats developed neuropathy, which was evident from thermal hyperalgesia and motor deficit. Administering SKE at a daily dose of between 50 and 200?mg/kg to the diabetic animals for 3?weeks ameliorated hyperglycemia, weight loss, hyperalgesia, and motor deficit, inhibited caspase 3 activation, and decreased the Bax/Bcl-2 ratio. The results suggest that SKE exerts neuroprotective effects against hyperglycemia-induced cellular damage. The mechanisms of these effects may be related to (at least in part) the prevention of neural apoptosis, and the results suggest that Satureja has the therapeutic potential to attenuate side effects of diabetes, such as neuropathy.     

Hydrogel Arrays and Choroidal Neovascularization Models for Evaluation of Angiogenic Activity of Vital Pulp Therapy Biomaterials

Introduction

This study intended to evaluate the angiogenic properties of vital pulp therapy materials including white mineral trioxide aggregate (WMTA), calcium hydroxide (Ca[OH]₂), Geristore (Den-Mat, Santa Maria, CA), and nano WMTA biomaterials.

A survey on pulmonary pathogens and their antibiotic susceptibility among cystic fibrosis patients

ObjectiveThis study was performed to investigate frequency and antimicrobial susceptibility of pulmonary pathogens in cystic fibrosis (CF) patients.Methods129 pediatric patients with CF were enrolled in this cross-sectional study. Microbiological cultures were performed based on sputum or pharyngeal swabs. Antibiotic susceptibilities of the isolated bacteria were determined by the disk diffusion method.ResultsThe main infecting pathogens were Pseudomonas aeruginosa (38.8%), Klebsiella pneumoniae (11.6%) and Staphyloccus areus (9.3%), respectively. The most active antibiotics included rifampin (91.7% susceptibility), vancomycin (85%) and imipenem (83.5%). Emerging resistance against aminoglycosides was observed.ConclusionRegarding in vitro susceptibility results, cyclic treatment of long-term oral azithromycin and inhaled tobramycin could prophylactically be applied, and during exacerbations, imipenem or ceftazidime in combination with an aminoglycoside such as amikacin could be considered the drugs of choice.     

Nodal monocytoid B-cell lymphoma (nodal marginal-zone B-cell lymphoma).

Benign monocytoid B cells are seen in lymph nodes in different types of lymphadenitis and they occur in the form of clusters within and around sinuses and in the interfollicular areas, but rarely completely surround benign follicles to produce a marginal-zone pattern. The cytologic hallmark of these cells is the presence of abundant pale to clear cytoplasm; these cells usually are of medium size, and they have a rather bland-appearing, irregular nuclei with inconspicuous nucleoli. Malignant monocytoid B-cell proliferations in a lymph node have been classified as monocytoid B-cell lymphomas (MBCL), which are now called nodal marginal-zone B-cell lymphoma (MZL) in the World Health Organization (WHO) classification. In the recently published clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma, 25 of 1,378 cases (1.8%) were classified as primary MZL, whereas four times as many cases (105 or 7.6%) were classified as low-grade mucosa-associated lymphoid tissue (MALT)-type lymphoma. Transformation to large-cell lymphoma at the time of diagnosis was seen in five of 25 (20%) cases of nodal MZL and in 32 of 105 (30%) cases of MALT-type lymphoma. Comparison of the clinical findings at presentation and the survival results indicate that nodal MZL is more aggressive clinically than low-grade MALT-type lymphoma. For example, patients with nodal MZL had a significantly higher incidence of advanced-stage disease, including peripheral and paraaortic lymphadenopathy, than those with MALT-type lymphoma. Moreover, patients with nodal MZL had lower 5-year overall survival and failure-free survival than patients with MALT type lymphoma. When analysis was restricted to those patients with zero to three adverse risk factors in the International Prognostic Index, patients with nodal MZL still had a significantly lower overall and failure-free survival at 5 years than patients with MALT-type lymphoma. We conclude that nodal MZL is a distinctive disease entity and is similar to other low-grade nodal lymphomas, such as the follicular or small lymphocytic lymphomas, but different than MALT-type lymphoma.     

Electrical stimulation of locus coeruleus strengthens the surround inhibition in layer V barrel cortex in rat

It is believed that locus coeruleus (LC) influences the sensory information processing. However, its role in cortical surround inhibitory mechanism is not well established. In this experiment, using controlled mechanical displacement of whiskers; we investigated the effect of electrical stimulation of LC on response of layer V barrel cortical neurons in anesthetized rat. LC was stimulated 0, 50, 100, 200 and 400 ms before principal or adjacent whiskers deflection. For assessing the effect of LC stimulation on inhibitory receptive filed of barrel neurons, adjacent whisker was also deflected 20 ms before principal whisker deflection, and LC stimulation was applied 0-400 ms before principal whisker displacement. We found that LC stimulation increase the response magnitude of layer V neurons to principal whisker deflection (significant in 50-400 ms intervals). This increase was also observed in response to adjacent whisker deflection (significant in 100 ms interval). The response latency of neurons was decreased when LC was stimulated 400 ms before principal whisker deflection but LC stimulation did not affect the neuronal response latency to adjacent whisker displacement. Inhibitory effect of adjacent whisker deflection on neuronal response magnitude was increased by LC stimulation, tested in combined whisker displacement. These findings suggest that LC, by modulating the neuronal responses, enhances the neuronal responsiveness to sensory stimuli and increases their surround inhibition in cortex.     

Maternal and neonatal outcomes after antenatal corticosteroid administration for PPROM at 32 to 33 6/7 weeks gestational age*

Background: Preterm Premature Rupture of Membranes (PPROM) precedes many deliveries and experts agree with expectant management until 34 weeks gestation. However, there is controversy regarding the gestational age (GA) for administration of corticosteroids.

Study design: We performed a retrospective cohort study in the University of California Fetal Consortium (UCfC). We searched available charts of singleton pregnancies with PPROM between 32 and 33 6/7 weeks GA. Outcomes from the groups were analyzed.

Results: Of 191 women with PPROM at 32 to 33 6/7 weeks, 150 received corticosteroids. The median GA at admission was earlier for the exposed versus unexposed group (32 4/7 versus 33 0/7 weeks, respectively, p?=?0.001). The mean GA at delivery in the exposed was 33 2/7 (32 0/7 to 35 0/7) weeks versus 33 5/7 (32 0/7 to 36 1/7) weeks in the unexposed (p?=?0.001). There was no difference in chorioamnionitis or RDS.

Conclusion: In women with PPROM at 32 to 33 6/7 weeks, our data suggests that corticosteroids are associated with similar outcomes despite earlier GA at delivery and no differences in major morbidities. A larger prospective study is needed to determine if the benefit of corticosteroids outweighs the potential risks in PPROM.     

Mesangial cell integrin αvβ8 provides glomerular endothelial cell cytoprotection by sequestering TGF-β and regulating PECAM-1

Integrins are heterodimeric receptors that regulate cell adhesion, migration, and apoptosis. Integrin αvβ8 is most abundantly expressed in kidney and brain, and its major ligand is latent transforming growth factor-β (TGF-β). Kidney αvβ8 localizes to mesangial cells, which appose glomerular endothelial cells and maintain glomerular capillary structure by mechanical and poorly understood paracrine mechanisms. To establish kidney αvβ8 function, mice with homozygous Itgb8 deletion (Itgb8(-/-)) were generated on outbred and C57BL/6 congenic backgrounds. Most Itgb8(-/-) mice died in utero, and surviving Itgb8(-/-) mice failed to gain weight, and rarely survived beyond 6 weeks. A renal glomerular phenotype included azotemia and albuminuria, as well as increased platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, which was surprisingly not associated with conventional functions, such as endothelial cell hyperplasia, hypertrophy, or perivascular inflammation. Itgb8(-/-) mesangial cells demonstrated reduced latent TGF-β binding, resulting in bioactive TGF-β release, which stimulated glomerular endothelial cell apoptosis. Using PECAM-1 gain and loss of function strategies, we show that PECAM-1 provides endothelial cytoprotection against mesangial cell TGF-β. These results clarify a singular mechanism of mesangial-to-endothelial cell cross-talk, whereby mesangial cell αvβ8 homeostatically arbitrates glomerular microvascular integrity by sequestering TGF-β in its latent conformation. Under pathological conditions associated with decreased mesangial cell αvβ8 expression and TGF-β secretion, compensatory PECAM-1 modulation facilitates glomerular endothelial cell survival.     

Further evidence that "malignant angioendotheliomatosis" is an angiotropic large-cell lymphoma

Malignant angioendotheliomatosis is a rare, generally fatal disease characterized by a multifocal proliferation of neoplastic mononuclear cells within the lumens of small blood vessels. Although the disease primarily involves the vasculature of the skin and central nervous system, vascular involvement of other organs may occur and may produce a variety of clinical findings. Some early investigators concluded that malignant angioendotheliomatosis was a neoplasm of endothelial cells, but recently others have suggested that it is of hematopoietic origin. We have studied three patients with the disease and have characterized the immunophenotype of the neoplasm on cryostat-cut fresh-frozen tissues. A detailed antigenic phenotyping of neoplastic lymphoid cells showed that one patient had the immunophenotype T11+, Leu-1+, Leu-3+, Leu-2+, B1-, B2-, SIg-, LN1-, LN2-, the predominant phenotype for peripheral T-cell lymphoma; the others had T11-, Leu-1-, Leu-3-, Leu-2-, B1+, B2+, SIg+, LN1+, LN2+, consistent with a B-cell-derived lymphoma. On the basis of our results, we suggest that angiotropic (intravascular) large-cell lymphoma would be more appropriate than malignant angioendotheliomatosis as a name for this disease.