The ameliorative role of Aloe vera-loaded chitosan nanoparticles on Staphylococcus aureus induced acute lung injury: Targeting TLR/NF-κB signaling pathways.

Background: Acute lung injury (ALI) is a severe condition distinguished by inflammation and impaired gas exchange in the lungs. Staphylococcus aureus, a common bacterium, can cause ALI through its virulence factors. Aloe vera is a medicinal plant that has been traditionally used to treat a variety of illnesses due to its anti-inflammatory properties. Chitosan nanoparticles are biocompatible and totally biodegradable materials that have shown potential in drug delivery systems. Aim: To explore the antibacterial activity of Aloe vera-loaded chitosan nanoparticles (AV-CS-NPs) against S. aureus in vitro and in vivo with advanced techniques. Methods: The antibacterial efficacy of AV-CS-NPs was evaluated through a broth microdilution assay. In addition, the impact of AV-CS-NPs on S. aureus-induced ALI in rats was examined by analyzing the expression of genes linked to inflammation, oxidative stress, and apoptosis. Furthermore, rat lung tissue was scanned histologically. The rats were divided into three groups: control, ALI, and treatment with AV-CS-NPs. Results: The AV-CS-NPs that were prepared exhibited clustered semispherical and spherical forms, having an average particle size of approximately 60 nm. These nanoparticles displayed a diverse structure with an uneven distribution of particle sizes. The maximum entrapment efficiency of 95.5% ± 1.25% was achieved. The obtained findings revealed that The minimum inhibitory concentration and minimum bactericidal concentration values were determined to be 5 and 10 ug/ml, respectively, indicating the potent bactericidal effect of the NPs. Also, S. aureus infected rats explored upregulation in the mRNA expression of TLR2 and TLR4 compared to healthy control groups. AV-CS-NP treatment reverses the case where there was repression in mRNA expression of TLR2 and TLR4 compared to S. aureus-treated rats. Conclusion: These NPs can serve as potential candidates for the development of alternative antimicrobial agents.

TGF-ß1, NAG-1, and antioxidant enzymes expression alterations in Cisplatin-induced nephrotoxicity in a rat model: Comparative modulating role of Melatonin, Vit. E and Ozone.

Cisplatin (CP) is an anticancer medication that is commonly used to treat solid tumors. Its use is, however, dose-restricted due to nephrotoxicity. We planned to compare the nephroprotective effects of three major compounds, including melatonin (MN), Ozone, or vitamin E, against the CP-induced renal damage in rats. CP was given once intraperitoneally (10 mg/kg,) eliciting acute kidney injury as assured by several adverse histological changes; glomerulopathy, tubulopathy, and vasculopathy, an inflammatory response including elevated TNF-α, IL-6, and IL-1ß. Furthermore, biochemical alterations including, elevated plasma levels of urea, uric acid, creatinine, phosphorous, decreased plasma calcium levels, and gene expression abnormalities; upregulation of N-acetyl-ß-d-glucosaminidase (NAG) and Transforming growth factor-ß1 (TGF-ß1), downregulation of CAT and SOD. Concurrent supplementation with either MN (10 mg/kg per os) or Ozone (1.1 mg/kg ip) and Vit E given by oral gavage (1 g/kg) for five consecutive days prior to CP injection and five days afterward displayed variable significant nephroprotective effects by mitigating the pro-inflammatory secretion, augmenting antioxidant competence, and modulating the gene expression in the renal tissue. The obtained biochemical, histological, and gene expression data suggested that MN had foremost rescue effects followed by Ozone then Vit E. MN's ameliorative effect was augmented in many indices including TNF-α, IL-6 , IL1-ß, uric acid, creatinine, sNGAL and GGT, more than observed in Ozone, and Vit E therapy. A combination of these medications is expected to be more useful in relieving the damaging renal effects of CP given to cancer patients, pending further toxicological and pharmacological research.

Arbuscular mycorrhiza and environmentally biochemicals enhance the nutritional status of Helianthus tuberosus and induce its resistance against Sclerotium rolfsii.

Chemical fungicides are effective tools in controlling plant pathogens; however, these chemicals can, on the other hand, distress the ecosystem. Accordingly, the current research investigates the potentiality of substituting traditional chemical fungicides by inducing plant resistance against infection with soil-born pathogens i.e. Sclerotium rolfsii in the presence of mycorrhizae (AMF) as plant inoculants and one of the following amendments: humic acid, sulphex (a mixture of canola oil and diluted sulphuric acid) and paclobutrazol (ABZ). To attain the abovementioned objective, a field (mildly infected with S. rolfsii) was cultivated with Helianthus tuberosus (a perennial plant belongs to the Asteraceae family) for two successive seasons (2014 and 2015) and the above-mentioned treatments were tested for their feasibilities in controlling S. rolfsii infection against the chemical fungicide "Vitavax-200" either solely or in combinations in a complete randomized block design. Inoculating plants with AMF or amending soils with either humic acid, Sulphex or ABZ solely increased significantly the activities of plant defense enzymes by approximately 1.5-2.1 folds higher than the control treatment. These treatments also improved NPK availability in soil and; hence, increased their contents within plant tubers. Consequently, these treatments decreased the disease incidence and severity caused by S. rolfsii while improved shoot biomass and tuber yield. In spite of that, these results stood below the prospective of the fungicide treatment. The integrated treatments i.e. "humic acid + AMF", "Sulphex + AMF" and "ABZ + AMF" caused further significant improvements in both NPK availabilities in soil and plant areal bio-masses. This probably induced further plant resistance against the investigated soil-borne pathogen while recorded insignificant variations in disease incidence and severity when compared with the fungicide treatment. Moreover, the integrated treatments increased the tuber yields beyond those attained for the fungicide treatment. Accordingly, such integrated strategies can completely substitute the chemical fungicides; thus, minimize their negative impacts on the ecosystem.

Identification of a novel class of covalent modifiers of hemoglobin as potential antisickling agents.

Aromatic aldehydes and ethacrynic acid (ECA) exhibit antipolymerization properties that are beneficial for sickle cell disease therapy. Based on the ECA pharmacophore and its atomic interaction with hemoglobin, we designed and synthesized several compounds - designated as KAUS (imidazolylacryloyl derivatives) - that we hypothesized would bind covalently to ßCys93 of hemoglobin and inhibit sickling. The compounds surprisingly showed weak allosteric and antisickling properties. X-ray studies of hemoglobin in complex with representative KAUS compounds revealed an unanticipated mode of Michael addition between the ß-unsaturated carbon and the N-terminal αVal1 nitrogen at the α-cleft of hemoglobin, with no observable interaction with ßCys93. Interestingly, the compounds exhibited almost no reactivity with the free amino acids, L-Val, L-His and L-Lys, but showed some reactivity with both glutathione and L-Cys. Our findings provide a molecular level explanation for the compounds biological activities and an important framework for targeted modifications that would yield novel potent antisickling agents.

Reduction and internal fixation for acute midshaft clavicular fractures by mini-incision using cannulated screws.

UNLABELLED: Open reduction and internal fixation of fracture clavicle has typically been done by variable types of plates. Plates carry the disadvantages of longer incisions, prominence of the plates and wound complications. The purpose of this study is to present an alternative surgical technique for acute midshaft clavicular fracture using cannulated 6.5 screws with minimal incision over the fracture site. Twenty seven adult patients with acute midshaft clavicular fractures were surgically treated with mini open technique using 6.5mm cannulated screws. The modified shoulder rating scale by Chuang was used for outcome evaluation. Union occurred in a mean of 8.3 weeks range 6-12 weeks. Restoration of clavicular length was achieved in all cases. Twenty-four patients experienced no pain on all activity at latest follow-up. All patients expressed their willingness to have the surgery again should they have the same problem. One patient stated that she would not have the surgery again. CONCLUSION: reduction and internal fixation with a cannulated screw is an alternative economic technique for the treatment of acute midshaft clavicular fractures that is useful in selected cases where surgery is indicated.

A study of ApaI and TaqI genotypes of the vitamin D receptor in Egyptian patients with psoriasis.

BACKGROUND: Vitamin D analogues have been found to be effective in treating the skin lesions of psoriasis. The therapy is thought to work through the vitamin D receptors, resulting in alteration of the proliferation/differentiation balance of the cells. Vitamin D also has an effect on T helper cells, which have a major role in the pathogenesis of psoriasis. There is controversy about the association of vitamin D receptor gene polymorphisms with psoriasis in different populations, and it is a factor that might influence the treatment of these patients. AIM: To study vitamin D receptor gene polymorphisms using two restriction enzymes in a group of Egyptian patients with psoriasis. METHODS: In total, 50 patients with psoriasis were examined using restriction fragment length polymorphism analysis to study ApaI and TaqI genotypes of the vitamin D receptor in a sample of Egyptian patients, and compared with 50 healthy control subjects. RESULTS: We did not find any significant difference in ApaI and TaqI vitamin D receptor gene polymorphisms between patients and controls. CONCLUSIONS: There is ethnic variability in vitamin D receptor gene polymorphisms. The lack of significant prevalence of the studied gene polymorphisms in our population suggests that their association with other functionally known gene polymorphism might have a role in the pathogenesis of psoriasis.

Avoiding over diagnosis of shoulder dystocia.

In this study, we aimed to distinguish true shoulder dystocia from mere difficulty with delivery of the shoulder, by investigating the risk factors that lead to shoulder dystocia. Shoulder dystocia is a bony problem which occurs when either the anterior or, less commonly, the posterior fetal shoulder impacts on the maternal symphysis pubis or sacral promontory. Failure to apply the Royal College of Obstetricians and Gynaecologists (RCOG) clinical diagnostic criteria for shoulder dystocia has made it susceptible to over-diagnosis due to inclusion of all difficult shoulder deliveries, including those related to an inappropriate maternal position. This was a retrospective analysis of risk factors associated with 56 cases of shoulder dystocia which occurred in West Middlesex University Hospital between 2003 and 2004. The cases were analysed in two categories, good outcome and poor outcome, and compared with each other. The poor outcome had represented true shoulder dystocia. The incidence of shoulder dystocia increased from 0.94% in 2003 to 1.37% in 2004. However, the incidence of those with a poor outcome decreased from 45.4% of the whole shoulder dystocia group in 2003, to 17.6% in 2004 (p = 0.03). There were no clear diagnostic criteria documented in the notes for the condition other than the birth attendants' opinion and the turtle sign. This may either reflect over-diagnosis from increased awareness or possibly improvement in the outcome due to training and education. Interestingly, at least four risk factors were identified in each of the cases with poor outcome. A registrar conducting the delivery, forceps delivery for delayed second stage and the turtle sign were significantly common findings among the true shoulder dystocia group. Multiple risk factors can be a good predictor for the occurrence of shoulder dystocia. Applying the RCOG diagnostic criteria for shoulder dystocia may lead to improvement in diagnosis and therefore a better understanding of the risk factors and future management of shoulder dystocia.

Expression of the apoptosis inhibitor Bcl-2 in sputum eosinophils from children with acute asthma.

BACKGROUND: Apoptosis of eosinophils is of increasingly important value in modulating allergic airway inflammation in asthma. Our purpose was to investigate the degree of expression of the antiapoptotic B-cell lymphoma/leukaemia-2 (Bcl-2) protein in sputum eosinophils during acute asthma exacerbation and its relationship with exacerbation severity. METHODS: Sputum was obtained from 33 asthmatic children and 15 healthy children as a control group. Patients were studied during an acute asthma exacerbation. They were classified according to the severity of exacerbation into mild, moderate and severe (n=11 for each). Patients with severe exacerbation were followed up until remission and another sputum sample was obtained. Number of sputum eosinophils was expressed as percentage of leucocytes. Bcl-2 expression in sputum eosinophils was assessed by immunohistochemical staining techniques; the results were expressed as percentage of positively stained cells over total eosinophils. RESULTS: Sputum eosinophils and Bcl-2(+) eosinophils' percentages were significantly higher in patients with acute exacerbation than controls (P<0.01). Patients with severe exacerbation had significantly higher sputum Bcl-2(+) eosinophils' percentage than those with mild-to-moderate exacerbation (mean+/-SD=42.4+/-31.96% vs. 5.7+/-14.5%, P<0.01). A significant negative correlation was found between Bcl-2(+) eosinophils' percentage and peak expiratory flow rate % predicted (P<0.05). After remission, patients with severe exacerbation showed a significant decrease of Bcl-2(+) eosinophils' percentage (P<0.05). CONCLUSION: Our findings suggest that Bcl-2 prolongs survival and decreases apoptosis of airway eosinophils in asthma especially during exacerbation. Eosinophil apoptosis and Bcl-2 represent a target for new and effective therapeutic strategies of asthma.

Synthesis of some new benzothiazole derivatives as potential antimicrobial and antiparasitic agents.

Several thiazolidinonyl benzothiazoles 8a-b and thiazolinylbenzothiazoles 9a-j were synthesized by the reaction of 2-(N-substituted thiocarbamoyl hydrazino) benzothiazoles 7a-d with chloroacetic acid or phenacyl bromide respectively. The intermediate compounds 7a-d were prepared in a good yield by the reaction of 2-hydrazinobenzothiazole (6) with phenylisothiocyanates. Synthesis of hydrazones 10a-c were performed by the reaction of 6 with the corresponding aldehydes. Trials to cyclize the obtained hydrazones 10a-c into the corresponding triazolo derivatives 11a-c were unsuccessful. Addition of 4-morphylino carbonyl chloride to compound 6 yielded the corresponding 2-acid hydrazide derivative 12. Some of the prepared compounds were screened for their anti-parasitic activity. Most of them showed reasonable antinematodal or schistosomicidal activity. In addition, antimicrobial screening of all of the prepared new compounds was performed against Staphylococcus aeurus ATCC 6538, Escherichia coli ATCC 8735 and Candida albicans ATCC 10321 but non of them was active.

Eclampsia: a leading cause of maternal mortality.

Eclampsia is the occurrence of generalized convulsions during pregnancy, labor or within seven days of delivery, not due to epilepsy or other convulsive disorders. It is largely a preventable disease provided the pregnant women get regular antenatal care. Despite all prevention measures, diagnostic modalities and intensive treatment, it is still one of the leading causes of maternal mortality in the developing world. In this review, we present definitions, epidemiologic data, pathophysiology, diagnosis and management of this life threatening condition.

Cystolitholapaxy versus cystolithotomy in children.

BACKGROUND: Primary vesical stones are common in children in developing countries. Cystolithotomy is the traditional treatment, but a percutaneous approach has been advocated. PATIENTS AND METHODS: Between January 1992 and March 1997, 52 male children with primary vesical stones were treated at our center. The patients were stratified retrospectively into two groups according to the procedure of stone removal. Group I (25 patients) were children who underwent open cystolithotomy, and group II (27 patients) were those who had endourologic treatment either by the transurethral route (11 children) or via suprapubic approached (16). The mean age at the time of diagnosis was 3.6 +/- 2.1 years. The stone size ranged from 0.7 to 2 cm (mean 1.2 +/- 0.7 cm). RESULTS: In all cases, the stones were removed successfully. The operative time was similar in the two groups. The hospital stay was significantly less after endourologic procedures than after open surgery (P < 0.05). In Group I, one patient had a small-intestinal injury, and in Group II, one patient had urethral rupture and extravasation during transurethral cystolitholapaxy. There were no early or late complications in Group I. However, in Group II, 4 patients (15%) developed early and late complications. Early morbidity was in the form of persistent leakage of urine from the suprapubic site in one patient and acute abdomen from the peritoneal urine leakage in another two patients who had the same approach. A stricture of the bulbous urethra was seen in one patient 1 year after transurethral stone disintegration. CONCLUSION: In spite of the improvement of endourologic instruments, open surgical removal of primary vesical stones in boys is still the mainstay of therapy.