Influence of rutin on biochemical alterations in hyperammonemia in rats

Flavonoids are non-nutritive dietary components that are widely distributed in plants. The present study was undertaken to examine the protective influence of rutin, a polyphenolic flavonoid, on oxidative stress during ammonium chloride (AC)-induced hyperammonemia by measuring the levels of oxidative damage as well as antioxidant status. The levels of tissue (liver, brain and kidney) lipid peroxides and the antioxidants (total thiols, catalase, reduced glutathione and glutathione peroxidase) were analyzed. Hyperammonemia was induced by daily intraperitoneal injections of AC at a dose of 100 mg/kg body weight for 8 weeks. Decreased levels of tissue lipid peroxidation accompanied with increased antioxidant levels in hyperammonemic rats were observed during oral administration of rutin (50 mg/kg body weight), which clearly shows the antioxidant property of rutin. The study of induction of the antioxidant status is considered to be a reliable marker for evaluating the antiperoxidative effect of the polyphenolic compound. Our present findings show the protective role of rutin against lipid peroxidation and suggest that rutin possesses antioxidant potential that may be used for therapeutic purposes.     

Distribution of sand flies in El-Nekheil province,in Al-Madinah Al-Munawwarah region,western of Saudi Arabia

An entomological survey for sand flies was conducted at an area of cutaneous leishmaniasis—El-Nekheil in Northeast Al-Madinah Al-Munawwarah, Saudi Arabia. Standardized sampling with Centers for Disease Control (CDC) light traps and sticky traps was employed to determine monthly trends in species composition, density, sex ratio, and reproductive status and Leishmania infection rate of vector sand flies. A total of 621 sand flies were collected from March 2006 to November 2007. Six species representing two genera were identified, three Phlebotomus species: P. papatasi, P. sergenti, and P. bergeroti; and three Sergentomyia species: S. antennata, S. sergenti, and S. shewtzi. Phlebotomus papatasi was the predominant anthropophagic species found and comprised more than 70% of the sand fly population. A population peak (June) was observed for this species. The density of P. papatasi intra-domiciliary was higher than extra-domiciliary stations and inflated by a greater proportion of female flies. Of 189 dissected Phlebotomus females, 43% were blood-fed. No Leishmania parasites were found. The proportion of gravid P. papatasi increased progressively during the 5-month period from May to September and averaged 38%. Proportions of gravid flies may be a valid indicator of the physiological age and epidemiologic importance of the vector sand fly population at this focus.     

The effect of low to moderate patient volume on very low-birth-weight outcomes in a level III-B neonatal intensive care unit

We studied the effect of a low- to moderate-volume, level III-B neonatal intensive care unit (NICU) on very low-birth-weight (VLBW) outcomes. We performed a retrospective analysis of the King Abdulaziz Hospital (KAH) NICU electronic database. Short-term outcomes of all inborn VLBW infants (501 to 1500 g) in the well-equipped, well-staffed KAH NICU (2003 to 2008) were benchmarked with data (1997 to 2002) from the National Institute of Children Health and Human Development and Neonatal Research Network (NICHD-NRN). Survival without major neonatal morbidity was defined as survival without bronchopulmonary dysplasia (BPD), grade III to IV intraventricular hemorrhage (IVH), and Bell's stage II to III necrotizing enterocolitis (NEC). The survival rates of VLBW infants at the KAH NICU ( N = 250) and the NICHD-NRN ( N = 18,153) were similar (84 versus 85%). A significantly higher rate of survival without major neonatal morbidity (80 versus 70%, P = 0.002) and lower rate of BPD (14 versus 22%, P = 0.005) were observed in KAH. The rates of grade III to IV IVH, Bell's stage II to III NEC, and late-onset sepsis were comparable in both cohorts. Our low- to moderate-volume, well-equipped, well-staffed, level III-B NICU achieved outcomes similar to the NICHD-NRN. Further study is warranted to ascertain how a lower-volume NICU achieved similar outcomes, as this could then be applied to quality improvement efforts.     

A comprehensive non‐invasive framework for automated evaluation of acute renal transplant rejection using DCE‐MRI

The objective was to develop a novel and automated comprehensive framework for the non‐invasive identification and classification of kidney non‐rejection and acute rejection transplants using 2D dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). The proposed approach consists of four steps. First, kidney objects are segmented from the surrounding structures with a geometric deformable model. Second, a non‐rigid registration approach is employed to account for any local kidney deformation. In the third step, the cortex of the kidney is extracted in order to determine dynamic agent delivery, since it is the cortex that is primarily affected by the perfusion deficits that underlie the pathophysiology of acute rejection. Finally, we use an analytical function‐based model to fit the dynamic contrast agent kinetic curves in order to determine possible rejection candidates. Five features that map the data from the original data space to the feature space are chosen with a k‐nearest‐neighbor (KNN) classifier to distinguish between acute rejection and non‐rejection transplants. Our study includes 50 transplant patients divided into two groups: 27 patients with stable kidney function and the remainder with impaired kidney function. All of the patients underwent DCE‐MRI, while the patients in the impaired group also underwent ultrasound‐guided fine needle biopsy. We extracted the kidney objects and the renal cortex from DCE‐MRI for accurate medical evaluation with an accuracy of 0.97 ± 0.02 and 0.90 ± 0.03, respectively, using the Dice similarity metric. In a cohort of 50 participants, our framework classified all cases correctly (100%) as rejection or non‐rejection transplant candidates, which is comparable to the gold standard of biopsy but without the associated deleterious side‐effects. Both the 95% confidence interval (CI) statistic and the receiver operating characteristic (ROC) analysis document the ability to separate rejection and non‐rejection groups. The average plateau (AP) signal magnitude and the gamma‐variate model functional parameter α have the best individual discriminating characteristics. Copyright © 2013 John Wiley & Sons, Ltd.     

A Golgi study of neurons in the camel cerebellum (Camelus dromedarius)

Neurons in the cerebellar cortex of camels were studied using modified Golgi impregnation methods. Neurons were classified according to their position, morphology of their soma, density and distribution of dendrites, and the course of their axons. Accordingly, eight types of neurons were identified. Three types were found in the molecular layer: upper and lower stellate cells and basket cells, and four types were found in the granular layer: granule cells, Golgi Type II cells, Lugaro cells, and unipolar brush cells. Only the somata of Purkinje cells were found in the Purkinje cell layer. The molecular layer is characterized by the presence of more dendrites, dendritic spines, and transverse fibers. Golgi cells also show extensive dendritic branching and spines. The results illustrate the neuronal features of the camel cerebellum as a large mammal living in harsh environmental conditions. These findings should contribute to advancing our understanding of species-comparative anatomy in achieving better coordination of motor activity.     

Genetic basis of neurodevelopmental disorders in 103 Jordanian families

We recruited 103 families from Jordan with neurodevelopmental disorders (NDD) and patterns of inheritance mostly suggestive of autosomal recessive inheritance. In each family, we investigated at least one affected individual using exome sequencing and an in-house diagnostic variant interpretation pipeline including a search for copy number variation. This approach led us to identify the likely molecular defect in established disease genes in 37 families. We could identify 25 pathogenic nonsense and 11 missense variants as well as 3 pathogenic copy number variants and 1 repeat expansion. Notably, 11 of the disease-causal variants occurred de novo. In addition, we prioritized a homozygous frameshift variant in PUS3 in two sisters with intellectual disability. To our knowledge, PUS3 has been postulated only recently as a candidate disease gene for intellectual disability in a single family with three affected siblings. Our findings provide additional evidence to establish loss of PUS3 function as a cause of intellectual disability.     

Gene therapy and uterine leiomyoma: a review

Leiomyomas (fibroids) are common estrogen-dependent uterine tumours that cause significant morbidity for women and a substantial economic impact on health delivery systems. Currently, there is no effective medical treatment option for this condition-hysterectomy is the mainstay of management. This is not an attractive choice for many women, especially patients desiring to preserve their fertility potential. Gene therapy is becoming a clinical reality, with more than 600 clinical trials worldwide. Researchers have recently attempted to develop a gene-therapy-based approach for the ablation of uterine fibroids. The localized nature of this condition and its accessibility using different imaging or endoscopic techniques make it an attractive target for direct delivery of gene-based vectors. Recent work from our laboratory suggests the potential use of a dominant-negative form of estrogen receptor (ER) to inactivate estrogen signalling in leiomyoma cells and induce apoptosis. Our in vivo data in a mouse model demonstrate the ability of an adenovirus-expressing dominant-negative ER to arrest leiomyoma growth. We and others also have described the utility of the herpes simplex virus-thymidine kinase (HSV-TK) plus ganciclovir (GCV) suicide gene-therapy system to effectively eradicate leiomyoma cells by utilizing the bystandard effect phenomena and the high expression of gap-junction protein in these tumours. Further work on rat models will pave the way for future leiomyoma gene-therapy clinical trials and allow the realization of gene therapy as a viable non-surgical option for this common problem in women's health.     

Characterization of the CD8+ T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4+ and CD8+ T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse strains and allow dissection of immune mechanisms by using transgenic and knockout mice that are mostly available on a C57BL/6 background, we characterized the specificity, level and functional capabilities of CD8+ T cells during primary and secondary responses in lung parenchyma, airways and spleens of C57BL/6 mice. During the primary response, epitopes were recognized originating from the matrix, fusion, nucleo- and attachment proteins, whereas the secondary response focused predominantly on the matrix epitope. C57BL/6 mice are less permissive for hRSV infection than BALB/c mice, yet we found CD8+ T cell responses in the lungs and bronchoalveolar lavage, comparable to the responses described for BALB/c mice.     

Evaluation of serum mesothelin in malignant and benign ovarian masses

Purpose

To evaluate the diagnostic accuracy of serum mesothelin levels in patients with ovarian masses in comparison to serum cancer antigen (CA) 125 levels.

Methods

This diagnostic accuracy study was conducted in a gynecological oncology unit at Ain Shams University Maternity hospital. Based on radiological and clinical findings, a total of 110 patients were consecutively recruited. Preoperative serum mesothelin levels were assessed using enzyme-linked immunosorbent assay (ELISA) technique, while CA125 levels were determined using electrochemiluminescence immunoassay. All patients underwent exploratory laparotomy. Preoperative serum levels of both markers were correlated to histopathological reports obtained from each patient.

Results

A total of 96 patients were finally analyzed. Of the included 96 patients, 58 (60.4 %) had a benign ovarian lesion, while 38 (39.6 %) had a malignant lesion. The median serum CA125 levels were significantly higher in patients with malignant ovarian lesions than in patients with benign ovarian lesions [335.5 mIU/mL (range 60–1,127 mIU/mL) versus 33.65 mIU/mL (range 10.36–174 mIU/mL), P < 0.001]. The median serum mesothelin level was significantly higher in patients with malignant ovarian lesions than in patients with benign ovarian lesions [104.1 nmol/L (range 6.5–215.4 nmol/L) versus 12.65 nmol/L (range 6.5–102 nmol/L), P < 0.001]. The diagnostic sensitivity and specificity for mesothelin and CA125 were 97.4 and 98.3 % and 97.4 and 56.9 %, respectively. The combination of mesothelin with CA125 did not add predictive value to mesothelin compared with mesothelin alone [same sensitivity (97.4 %) and same specificity (98.3 %)]. Serum mesothelin levels rather than serum CA125 levels were a significant predictor of early-stage ovarian malignancy [Area under the curve = 0.732, 95 % confidence interval (0.543–0.921), P = 0.031].

Conclusion

In ovarian cancer, mesothelin seemed to have the same sensitivity, but a higher specificity than CA125. Combination of mesothelin and CA125 had no advantage over mesothelin alone. Mesothelin rather than CA125 was a significant predictor of early-stage ovarian cancer (stage I/II).